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Advanced and Metastatic Prostate Cancer: Modern Treatment and New Hope

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A diagnosis of advanced or metastatic prostate cancer can be frightening. However, the treatment landscape has changed dramatically over the past decade.

Where doctors once relied mainly on testosterone-lowering treatment, we now have combinations of androgen deprivation therapy (ADT), modern androgen-receptor medicines, chemotherapy, targeted treatments, radioligand therapy and, for selected cancers, immunotherapy.

Importantly, these treatments are increasingly being used earlier and in combination, rather than waiting for one treatment to fail before introducing the next.

The aim is not simply to lower the PSA. It is to control the cancer for as long as possible while maintaining quality of life.

What does “advanced” prostate cancer mean?

Advanced prostate cancer is not one single condition.

Locally advanced prostate cancer

The cancer has grown beyond the prostate or into nearby structures but has not necessarily spread to distant organs.

Metastatic hormone-sensitive prostate cancer

The cancer has spread elsewhere in the body, commonly to:

  • lymph nodes
  • bones
  • lungs
  • liver or other organs

but remains sensitive to testosterone suppression.

This is often abbreviated to mHSPC or metastatic hormone-sensitive prostate cancer.

Metastatic castration-resistant prostate cancer

Over time, prostate cancer cells may learn to grow despite very low testosterone levels.

This is called metastatic castration-resistant prostate cancer (mCRPC).

“Castration resistant” does not mean that there are no further treatments available. Quite the opposite. We now have several effective treatment classes that can be used at this stage.

1. Androgen Deprivation Therapy: The Foundation of Treatment

Prostate cancer cells are usually heavily dependent on male hormones, particularly testosterone.

Androgen deprivation therapy (ADT) reduces testosterone to very low levels.

This can be achieved with regular injections or implants using GnRH/LHRH agonists or antagonists. Surgical removal of the testosterone-producing portion of the testes, called an orchidectomy, remains effective but is now used less frequently.

ADT remains the backbone of treatment for metastatic prostate cancer.

However, an important change in modern prostate cancer management is that ADT alone is usually no longer considered adequate initial treatment for a fit man presenting with metastatic hormone-sensitive disease.

Current EAU recommendations favour combining ADT with another effective systemic treatment whenever the patient is sufficiently fit.

2. Double Therapy

One approach combines ADT with a modern androgen-receptor pathway inhibitor (ARPI).

Examples include:

Abiraterone + prednisone

Abiraterone blocks androgen production not only from the testes but also from the adrenal glands and within the cancer itself.

Potential side effects include:

  • high blood pressure
  • low potassium
  • fluid retention
  • abnormal liver function
  • cardiac problems in susceptible patients
  • steroid-related effects

Enzalutamide

This blocks signalling through the androgen receptor.

Possible side effects include fatigue, hypertension, falls, cognitive effects and, rarely, seizures.

Apalutamide

Another potent androgen-receptor inhibitor. Side effects may include fatigue, rash, hypertension, falls and thyroid abnormalities.

Darolutamide

Darolutamide also inhibits androgen-receptor signalling and has relatively limited penetration into the central nervous system, which may be advantageous for some patients.

Current EAU guidance strongly supports treatment intensification rather than ADT alone in suitable patients with metastatic hormone-sensitive disease.

3. Triple Therapy: Three Treatments From the Starting Line

One of the biggest developments in metastatic prostate cancer has been triplet therapy.

Instead of:

ADT alone

or:

ADT + one additional treatment

selected patients may receive:

ADT + chemotherapy + an androgen-receptor pathway inhibitor

Two landmark trials helped establish this approach.

ARASENS

The phase III ARASENS trial investigated:

ADT + docetaxel + darolutamide

compared with:

ADT + docetaxel + placebo

The addition of darolutamide reduced the risk of death by approximately 32.5%, with a hazard ratio for death of 0.68.

Four-year overall survival was approximately 62.7% with triplet therapy compared with 50.4% in the control group.

PEACE-1

The PEACE-1 trial investigated the addition of abiraterone to standard treatment in men with newly diagnosed metastatic prostate cancer.

Among patients receiving ADT and docetaxel, adding abiraterone improved both radiographic progression-free survival and overall survival.

These studies have fundamentally changed how we approach a fit patient presenting with metastatic prostate cancer.

Who may benefit from triple therapy?

Triplet therapy is particularly considered in men who:

  • present initially with metastatic disease
  • have a significant metastatic burden
  • are medically fit enough to receive chemotherapy
  • have an expected lifespan sufficient to benefit from treatment intensification.

Treatment nevertheless needs to be individualised.

The EAU now recommends that when docetaxel is used for first-line metastatic hormone-sensitive disease, it should generally be given as part of combination treatment with ADT plus abiraterone or darolutamide in patients fit enough for chemotherapy.

One important scientific caveat remains: trials clearly demonstrated that triplet treatment is superior to ADT + docetaxel, but direct randomised evidence comparing triplet therapy against ADT + a modern ARPI without chemotherapy remains limited.

4. Chemotherapy

Docetaxel

Docetaxel remains an important chemotherapy for advanced prostate cancer.

It damages rapidly dividing cancer cells and is commonly given intravenously every three weeks for a defined number of cycles when used in hormone-sensitive metastatic disease.

Potential side effects include:

  • fatigue
  • temporary hair loss
  • lowered white blood cell count
  • infection
  • febrile neutropenia
  • anaemia
  • altered taste
  • nail changes
  • peripheral neuropathy
  • fluid retention.

Modern supportive treatment has made chemotherapy considerably more manageable than many patients expect.

Cabazitaxel

Cabazitaxel is generally used later, particularly when metastatic castration-resistant cancer has progressed following docetaxel and androgen-receptor pathway treatment.

Current ASCO recommendations include cabazitaxel as an important later-line treatment following appropriate prior ARPI and docetaxel therapy.

5. Should ADT Ever Be Intermittent?

This is an important question because ADT has significant long-term effects.

With intermittent ADT, treatment is stopped after a good PSA response and restarted when the PSA or cancer activity rises again.

The attraction is obvious: periods away from treatment may allow testosterone recovery and improvements in:

  • sexual function
  • hot flushes
  • energy
  • mood
  • muscle strength
  • metabolic health.

However, metastatic disease is different from some non-metastatic situations.

The large SWOG 9346 study could not establish that intermittent treatment was non-inferior to continuous ADT in metastatic disease. Consequently, a small survival disadvantage from intermittent therapy cannot be excluded.

The 2026 EAU guideline therefore notes that intermittent ADT has largely been superseded by continuous ADT-based combination therapy for metastatic disease.

For most men with metastatic prostate cancer, therefore, continuous hormonal suppression remains the standard.

Intermittent treatment may occasionally be considered in carefully selected circumstances after detailed discussion of the potential quality-of-life benefits and oncological uncertainty.

6. What Happens When the Cancer Becomes Castration Resistant?

A rising PSA despite very low testosterone does not automatically mean treatment has “stopped working.”

Rather, it tells us that the biology of the cancer has changed.

Importantly, ADT is usually continued even after castration resistance develops.

The next treatment depends heavily upon what the patient has already received.

Options can include:

  • docetaxel
  • cabazitaxel
  • abiraterone
  • enzalutamide
  • PARP inhibitors
  • radioligand therapy
  • radium-223
  • selected immunotherapy
  • clinical trials.

Simply moving repeatedly from one androgen-receptor drug to another is becoming less attractive because of significant cross-resistance.

7. Genetic Testing Has Become Part of Treatment

One of the most important changes in advanced prostate cancer management is the move toward precision medicine.

Men with metastatic disease should increasingly be considered for tumour genomic testing and, where appropriate, germline genetic testing.

Important abnormalities include mutations involving:

BRCA1, BRCA2 and other homologous recombination repair (HRR) genes.

These mutations may make the cancer susceptible to PARP inhibitors.

Examples include:

  • olaparib
  • niraparib
  • talazoparib
  • rucaparib in appropriate settings.

Some PARP inhibitors can now be combined with androgen-receptor treatments in appropriately selected patients.

The 2026 EAU guidelines specifically recommend testing metastatic patients for somatic or germline HRR abnormalities because the results may directly change treatment.

In other words, we increasingly need to know not only where the prostate cancer has spread, but what is driving it genetically.

8. Immunotherapy: Exciting, But Not for Everyone

Immunotherapy has transformed several cancers, but prostate cancer has proved more resistant to conventional immune checkpoint therapy.

For the average patient with metastatic prostate cancer, immunotherapy is not currently routine first-line treatment.

However, there is an important exception.

Pembrolizumab

A small proportion of prostate cancers have abnormalities known as:

  • MSI-high
  • mismatch-repair deficient (dMMR)
  • or, in relevant jurisdictions, sufficiently high tumour mutational burden.

These cancers may respond to the immune checkpoint inhibitor pembrolizumab.

ASCO’s 2026 living guideline recognises clinical activity of pembrolizumab in selected MSI-high/mismatch-repair-deficient metastatic castration-resistant prostate cancer.

This is another reason why molecular testing has become important.

For unselected prostate cancer patients, however, large trials combining pembrolizumab with treatments such as docetaxel, enzalutamide or olaparib have not demonstrated the hoped-for survival improvement.

Immunotherapy therefore currently works best as a biomarker-selected treatment rather than a universal prostate cancer therapy.

Possible immune-related side effects include inflammation of normal organs, including:

  • thyroid dysfunction
  • skin inflammation
  • colitis and diarrhoea
  • hepatitis
  • pneumonitis
  • adrenal or pituitary abnormalities.

Although uncommon, some immune complications can be serious and require corticosteroid treatment.

9. PSMA Radioligand Therapy

Another major advance is lutetium-177 PSMA radioligand therapy, often written as ¹⁷⁷Lu-PSMA-617.

The treatment uses a molecule that recognises PSMA on prostate cancer cells and carries a radioactive isotope directly to those cells.

It is therefore rather like delivering radiation with a molecular address label attached.

For appropriately selected men with PSMA-positive metastatic castration-resistant prostate cancer, it can provide another life-prolonging systemic treatment option.

The exact timing of ¹⁷⁷Lu-PSMA therapy is evolving rapidly as clinical trial evidence matures and regulatory indications change. Current EAU and ASCO recommendations include it among established systemic options for appropriately selected mCRPC patients.

Potential side effects include:

  • fatigue
  • dry mouth
  • nausea
  • reduced blood counts
  • anaemia
  • thrombocytopenia.

10. Radium-223 for Bone-Dominant Disease

Prostate cancer has a particular tendency to spread to bone.

Radium-223 is a radioactive treatment that preferentially targets areas of increased bone turnover.

It may be appropriate for selected men with symptomatic bone-predominant metastatic castration-resistant prostate cancer without visceral metastases.

Its role needs to be carefully coordinated with other treatments and bone-health management.

11. Don’t Forget the Prostate Itself

It may seem strange to treat the prostate once cancer has already spread.

However, clinical studies have demonstrated that treating the primary prostate tumour with radiotherapy can improve outcomes in selected men presenting with low-volume metastatic disease.

The EAU therefore recommends prostate radiotherapy for appropriately selected patients presenting with low-volume metastatic hormone-sensitive prostate cancer.

This does not mean every man with metastatic prostate cancer should have prostate surgery or radiation. The benefit depends on the pattern and burden of metastatic disease.

12. Side Effects of Long-Term Hormonal Treatment

Because men may now live for many years with advanced prostate cancer, treatment side effects deserve almost as much attention as the cancer itself.

Long-term ADT may cause:

Sexual effects

Reduced libido, erectile dysfunction and loss of spontaneous erections are common.

Hot flushes

These can range from mildly annoying to profoundly disruptive.

Muscle loss

Testosterone suppression causes loss of muscle mass and strength unless actively countered.

Weight gain

Fat tends to accumulate particularly around the abdomen.

Metabolic changes

ADT can increase the risk of:

  • insulin resistance
  • diabetes
  • abnormal cholesterol
  • cardiovascular disease.

Bone thinning

Long-term ADT accelerates osteoporosis and increases fracture risk.

Current EAU guidance recommends formal assessment of osteoporosis risk, including DEXA scanning when commencing long-term ADT, together with appropriate bone protection.

Mood and cognition

Some men experience:

  • fatigue
  • low mood
  • reduced motivation
  • sleep disturbance
  • difficulty concentrating.

These symptoms deserve recognition and treatment rather than being dismissed as simply part of ageing.

Exercise Is Part of Cancer Treatment

Regular exercise is one of the most useful supportive treatments for men receiving long-term ADT.

A programme incorporating:

resistance training + aerobic exercise + balance work

can help preserve muscle, bone strength, cardiovascular fitness and independence.

Nutrition, weight management, smoking cessation, alcohol moderation and optimisation of cardiovascular risk factors should form part of long-term prostate cancer care.

Bone Health Matters

Men receiving prolonged ADT should have their fracture risk assessed.

Depending on bone density and metastatic involvement, treatment may include:

  • calcium and vitamin D when appropriate
  • resistance and weight-bearing exercise
  • bisphosphonates
  • denosumab.

Men receiving denosumab or bisphosphonates require appropriate calcium monitoring and usually dental assessment because of the uncommon but important risk of osteonecrosis of the jaw.

A New Way of Thinking About Metastatic Prostate Cancer

The old treatment pathway was fairly linear:

ADT → wait for progression → chemotherapy → another treatment.

Modern treatment looks very different.

It is increasingly:

Diagnose → accurately stage → molecularly profile → intensify treatment early → continuously reassess → select the next therapy according to previous treatment and tumour biology.

For some patients this means:

ADT + ARPI

For others:

ADT + docetaxel + darolutamide

or:

ADT + docetaxel + abiraterone

And later, depending on the tumour:

chemotherapy → PARP inhibition → PSMA radioligand therapy → radium-223 → selected immunotherapy or clinical trials.

There is no longer a single treatment pathway that suits every patient.

The Bottom Line

Advanced prostate cancer remains a serious disease, but its treatment has undergone a remarkable transformation.

The strongest contemporary evidence supports early treatment intensification for suitable men with metastatic hormone-sensitive prostate cancer rather than relying on ADT alone.

The ARASENS and PEACE-1 trials established an important role for triplet therapy in appropriately selected patients, while modern guidelines increasingly emphasise genomic testing, targeted treatment, radioligand therapy and careful sequencing of chemotherapy and androgen-receptor treatments.

Intermittent ADT is attractive from a quality-of-life perspective but is not the routine standard for metastatic disease, where continuous ADT-based combination treatment remains preferred.

Perhaps most importantly, treatment should not focus exclusively on the PSA.

Bone health, cardiovascular health, muscle strength, sexual health, psychological wellbeing and maintaining independence are all part of successful prostate cancer treatment.

For many men, metastatic prostate cancer can now be controlled for years through carefully planned sequences and combinations of treatment.

This information is intended for general patient education. Treatment of advanced prostate cancer should be individualised through discussion with a urologist, medical oncologist and radiation oncologist experienced in prostate cancer management.

Penile Cancer: Symptoms, Diagnosis and Treatment in Australia

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Penile cancer is rare, but early diagnosis matters

Penile cancer is an uncommon cancer affecting the skin and tissues of the penis. In Australia, approximately 165 men were estimated to be diagnosed with penile cancer in 2025, with the average age at diagnosis around 68 years. About 95% of penile cancers are squamous cell carcinomas (SCC).

Although the diagnosis can understandably be frightening, there is an important message:

When penile cancer is detected early, treatment is frequently curative and, in many men, much or all of the penis can be preserved.

Modern treatment has therefore moved increasingly towards penile-preserving therapy whenever this can be achieved safely.

Treatment in Australia will depend on:

  • whether the abnormality is precancerous or invasive cancer
  • the size and location of the tumour
  • how deeply it has invaded
  • the grade of the cancer
  • whether lymph nodes in the groin are involved
  • whether cancer has spread elsewhere
  • the man’s general health and personal preferences.

Because penile cancer is rare, patients with invasive or complicated disease benefit from discussion by a multidisciplinary team (MDT) involving urology, medical oncology, radiation oncology, radiology, pathology and specialist nursing.

 

What causes penile cancer?

There is rarely one single identifiable cause.

Important risk factors include:

  • infection with human papillomavirus (HPV)
  • smoking
  • phimosis, where the foreskin cannot be retracted
  • chronic inflammation of the penis
  • penile intraepithelial neoplasia (PeIN)
  • increasing age
  • some chronic penile skin disorders
  • immunosuppression.

HPV plays an important role in a proportion of penile cancers, although penile cancer can certainly occur without HPV infection.

What symptoms should men look for?

Penile cancer often begins as a visible or palpable abnormality, particularly involving the glans or foreskin.

Symptoms can include:

  • a red or discoloured area that does not disappear
  • persistent irritation or inflammation
  • thickening of the skin
  • a lump
  • a wart-like growth
  • an ulcer or sore that does not heal
  • bleeding
  • persistent discharge
  • an unpleasant smell from beneath the foreskin
  • increasing difficulty retracting the foreskin
  • pain or tenderness
  • swelling of the end of the penis
  • a lump beneath the foreskin
  • enlarged lymph nodes or lumps in the groin.

More advanced disease can occasionally cause difficulty passing urine, fatigue or unexplained weight loss.

A persistent penile lesion deserves examination

Most rashes, spots and lumps on the penis are not cancer. Infection, inflammation, dermatitis and benign skin conditions are much more common.

The important issue is persistence.

A penile ulcer, lump, bleeding area or unusual skin change that does not resolve should not be hidden away in the hope that it will disappear.

Embarrassment is considerably easier to treat than advanced cancer.

How is penile cancer diagnosed?

Examination

The first step is careful examination of the penis and foreskin.

The urologist will assess:

  • the site of the lesion
  • its size
  • whether it involves the glans, foreskin or shaft
  • whether deeper tissues appear involved
  • whether the foreskin can be retracted
  • whether there are enlarged lymph nodes in either groin.

Both groins are particularly important because penile cancer usually spreads first through the lymphatic system to the inguinal lymph nodes.

Biopsy

The diagnosis usually requires a biopsy.

A small piece of the abnormal tissue is removed and examined by a pathologist.

Depending upon the lesion, this may be:

  • a punch biopsy
  • an incisional biopsy, taking part of the lesion
  • an excisional biopsy, removing the whole small lesion.

A biopsy determines whether cancer is present and, importantly, identifies the type and grade of the tumour.

Histological confirmation is particularly important before treatments such as topical therapy, laser treatment or radiotherapy.

What is PeIN?

Penile intraepithelial neoplasia (PeIN) is a precancerous or very early cancerous change confined to the surface epithelium.

It has previously been described using terms such as carcinoma in situ.

PeIN is important because it can progress to invasive squamous cell carcinoma. Current European guidelines estimate progression to invasive disease despite treatment in approximately 2.6–13% of patients.

The good news is that PeIN can often be treated without removing part of the penis.

Treatment: from creams to major surgery

There is no single operation or treatment for penile cancer.

Modern management follows a ladder, beginning with the least invasive treatment capable of reliably controlling the cancer.

1. Circumcision

For abnormalities confined to the foreskin, circumcision may remove the lesion completely.

Circumcision is also frequently an important first step when PeIN involves the glans and foreskin because it allows the glans to be properly examined and treated.

For superficial disease, contemporary guidelines regard circumcision as an important primary surgical treatment.

2. Treatment with creams

Selected cases of biopsy-confirmed PeIN can be treated with medication applied directly to the penis.

The two most commonly used treatments are:

5-fluorouracil (5-FU)

5-FU is a topical chemotherapy medication.

It destroys abnormal rapidly dividing cells in the superficial layers of the penis.

Treatment usually produces inflammation of the treated area, which can include:

  • redness
  • burning
  • crusting
  • discomfort
  • erosion of the surface skin.

Imiquimod

Imiquimod is different. Rather than being conventional chemotherapy, it stimulates the local immune system to attack abnormal cells.

It can similarly cause substantial redness, swelling, ulceration or crusting during treatment.

These reactions can look alarming but often indicate that the medication is producing its intended biological effect.

Current EAU-ASCO guidance supports either 5-FU or imiquimod for appropriately selected biopsy-confirmed PeIN.

Importantly, the area must be reassessed after treatment.

If the abnormality persists, repeat biopsy or alternative treatment may be necessary. Repeated courses of topical treatment should not simply continue indefinitely when the lesion has failed to respond, because invasive cancer may be hiding beneath the surface.

3. Laser and other local treatments

Very superficial lesions can sometimes be treated using laser therapy.

Depending upon expertise and availability, other local treatments such as photodynamic therapy or cryotherapy have also been used.

These approaches can preserve the penis but require careful long-term surveillance because local recurrence is possible.

4. Penile-preserving surgery

One of the major changes in penile cancer surgery has been the move away from automatically removing a substantial portion of the penis.

Whenever oncologically safe, the aim is:

remove the cancer, obtain clear margins and preserve as much normal penis as possible.

Operations may include:

Wide local excision

The cancer and a margin of surrounding tissue are removed.

The defect may be closed directly or reconstructed with a skin graft.

Glans resurfacing

The abnormal surface layer of the glans is removed while preserving the deeper erectile tissue.

A skin graft is then placed over the glans.

This can be particularly useful for extensive superficial disease.

Glansectomy

If cancer is confined to the glans but is too extensive or invasive for simpler treatment, part or all of the glans may be removed.

Reconstruction can then be performed, often using a skin graft to create a new glans-like surface.

Current guidelines favour organ-preserving surgery for appropriately selected PeIN and T1–T2 tumours involving the glans or prepuce, provided the patient understands the need for careful follow-up.

5. Partial penectomy

More deeply invasive cancer may require removal of part of the penis.

This is called a partial penectomy.

The surgeon attempts to retain enough penile length to permit comfortable urination and, where possible, sexual function.

This may be necessary when cancer extends more deeply into the erectile tissues and cannot be reliably removed using penile-preserving techniques.

6. Total penectomy

Occasionally a cancer is too large, too proximal or too deeply invasive for part of the penis to be safely preserved.

A total penectomy may then provide the best opportunity for cure.

This understandably sounds confronting. It is generally reserved for circumstances in which less radical treatment would compromise cancer control.

Current EAU-ASCO recommendations support total penectomy with perineal urethrostomy for large invasive tumours that cannot safely be treated by partial penectomy.

What is a perineal urethrostomy?

This is sometimes mistakenly referred to as a “perineotomy”.

Following total removal of the penis, urine still needs a pathway from the bladder to the outside world.

The urethra is therefore brought to the skin of the perineum, the area between the scrotum and anus.

This opening is called a:

Perineal urethrostomy

The patient subsequently passes urine through this opening while sitting on the toilet.

A catheter is generally left temporarily while the area heals.

Once healed, most men can empty their bladder normally through the new opening and do not require a permanent catheter.

Potential problems include:

  • narrowing or stenosis of the opening
  • spraying
  • infection
  • wound complications
  • occasionally the need for further surgery.

A perineal urethrostomy does not mean that the bladder or kidneys have stopped functioning. It simply changes the final few centimetres of the urinary plumbing.

The lymph nodes are extremely important

Treating the penis itself is only one half of penile cancer management.

The other half is determining whether cancer has reached the inguinal lymph nodes in the groin.

Penile cancer generally spreads in a predictable sequence:

Penis → inguinal lymph nodes → pelvic lymph nodes → distant organs

Lymph-node involvement is the single most important prognostic factor in penile cancer.

What if there are no enlarged lymph nodes?

Unfortunately, normal-feeling groins do not completely exclude microscopic cancer.

Men with higher-risk primary tumours may therefore require further lymph-node assessment despite having no palpable lumps.

This may involve:

  • ultrasound of the groins
  • ultrasound-guided needle biopsy of abnormal nodes
  • dynamic sentinel lymph-node biopsy
  • inguinal lymph-node dissection in selected circumstances.

Current EAU-ASCO guidance recommends surgical lymph-node staging for patients at significant risk of microscopic metastatic disease, particularly T1b disease or higher.

What if a groin lymph node is enlarged?

An abnormal lymph node may be assessed using ultrasound and needle biopsy.

If metastatic penile cancer is confirmed, treatment may involve:

  • inguinal lymph-node dissection
  • pelvic lymph-node dissection in selected patients
  • chemotherapy
  • radiotherapy
  • combinations of these treatments.

Patients with clinically node-positive disease are generally staged with CT or FDG-PET/CT to assess pelvic and distant disease before definitive treatment.

Early treatment of lymph-node disease is extremely important.

Radiation therapy

Radiotherapy has an important but selective role in penile cancer.

Treatment of the primary cancer

Selected smaller T1 or T2 cancers can potentially be treated with radiation instead of surgery.

Treatment can involve:

External beam radiotherapy

Radiation is directed at the tumour from outside the body.

Brachytherapy

Radioactive sources are temporarily positioned within or very close to the tumour, allowing a concentrated radiation dose to be delivered while limiting exposure to surrounding tissues.

Radiotherapy may therefore provide another means of preserving the penis in appropriately selected patients.

Potential complications can include:

  • skin irritation
  • ulceration
  • fibrosis
  • narrowing of the urethra
  • changes in penile sensation
  • erectile dysfunction
  • tissue damage or necrosis in uncommon circumstances.

Radiotherapy is also used in selected patients for regional lymph-node disease, as part of chemoradiotherapy for advanced disease, or for palliation of symptoms from metastatic cancer.

Chemotherapy

Chemotherapy is generally reserved for more advanced penile cancer, particularly when significant lymph-node disease or metastatic disease is present.

In Australia, contemporary treatment may involve platinum-based combination chemotherapy.

One regimen used in advanced disease is:

TIP: paclitaxel + ifosfamide + cisplatin

Australia’s eviQ cancer treatment resource includes TIP as an option in neoadjuvant, adjuvant and metastatic penile cancer settings.

For bulky or fixed inguinal lymph-node disease or pelvic lymph-node involvement, chemotherapy may be given before surgery.

This is called neoadjuvant chemotherapy.

The aim is to:

  1. treat microscopic disease throughout the body,
  2. shrink the cancer in the lymph nodes,
  3. determine whether the cancer is responding,
  4. make subsequent surgery more effective or technically achievable.

Current international guidance recommends cisplatin- and taxane-based neoadjuvant chemotherapy for suitable patients with extensive inguinal or pelvic nodal disease, followed by surgery when appropriate.

Chemoradiotherapy

Radiotherapy and chemotherapy can sometimes be combined.

This may be considered for selected patients with:

  • locally advanced disease
  • unresectable cancer
  • extensive lymph-node disease
  • disease where major surgery is unsuitable
  • palliative treatment requirements.

The evidence is evolving, and these decisions should generally be made through a specialist penile cancer MDT.

What about immunotherapy?

Immunotherapy is an exciting area of cancer treatment, but its role in penile cancer is still developing.

Checkpoint inhibitors such as pembrolizumab and related drugs have demonstrated activity in some patients with advanced penile cancer, and newer combinations of chemotherapy and immunotherapy are being investigated.

However, response rates to checkpoint inhibitors alone are relatively modest and there is not yet sufficient evidence to use biomarkers such as HPV or PD-L1 routinely to determine which penile cancer patients should receive immunotherapy.

Clinical trials are particularly important for men whose cancer progresses despite standard platinum-based chemotherapy.

What happens to sexual function?

This depends enormously on treatment.

After topical treatment, circumcision, laser therapy, glans resurfacing or limited local excision, satisfactory sexual function may often be preserved.

After glansectomy or partial penectomy, intercourse may remain possible depending upon remaining penile length, erectile function and reconstruction.

After total penectomy, penetrative intercourse using the penis is no longer possible.

This does not mean that intimacy, sexual sensation or orgasm automatically disappears.

Sexual rehabilitation, psychological support and discussion with the patient and his partner can be an important component of recovery.

These conversations should ideally begin before treatment, not after it.

What is the prognosis?

Penile cancer is potentially highly curable when diagnosed before it has spread to lymph nodes.

The most important predictor of survival is not simply the size of the penile lesion but whether cancer has reached the lymph nodes.

Current EAU-ASCO data report approximate five-year cancer-specific survival according to nodal stage of:

Lymph-node stage Approximate 5-year cancer-specific survival
N0 – no lymph-node metastases 95%
N1 80%
N2 65%
N3 – advanced nodal disease 35%

These are population figures, not predictions for an individual patient.

Prognosis depends upon the tumour’s stage and grade, lymph-node involvement, response to treatment, general health and other pathological features.

The figures do, however, demonstrate why early diagnosis and appropriate assessment of the groin lymph nodes are so important.

Follow-up after treatment

Penile cancer requires ongoing surveillance.

Follow-up may include:

  • examination of the penis or reconstructed area
  • examination of both groins
  • assessment of the perineal urethrostomy where applicable
  • imaging in higher-risk patients
  • biopsy of suspicious recurrent lesions
  • monitoring urinary and sexual function
  • psychological and sexual-health support.

Penile-preserving treatment requires particularly careful surveillance because local recurrence can occur.

Importantly, a local recurrence identified early can often still be successfully treated.

Do not ignore a change in the penis

Penile cancer is uncommon, and most penile skin problems are benign.

Nevertheless, a persistent:

lump, ulcer, red patch, bleeding area, discharge, thickened foreskin or lesion that simply will not heal deserves examination.

There should be no embarrassment in asking your GP or urologist to have a look.

For early disease, treatment may be surprisingly conservative: sometimes circumcision, a cream, laser treatment or limited surgery is all that is required.

Even when invasive cancer is present, modern penile cancer surgery increasingly focuses on preserving penile tissue, urinary function and quality of life whenever this can be achieved without compromising cure.

For advanced disease, treatment becomes more complex and may involve partial or total penectomy, perineal urethrostomy, lymph-node surgery, radiotherapy and chemotherapy.

The crucial message is simple:

The earlier penile cancer is diagnosed, the greater the opportunity to cure it while preserving the penis.

Australian and international resources

Cancer Council Australia: Penile Cancer

Cancer Institute NSW: Penile Cancer

eviQ Australian Penile Cancer Chemotherapy Protocol

2026 EAU-ASCO Penile Cancer Guidelines

This information is intended for patient education and does not replace individual medical assessment. Treatment of penile cancer should be tailored to the tumour stage, pathology, lymph-node status, general health and preferences of the individual patient.

So, if you have noticed a lesion on your penis and it is growing, don’t ignore it and hope it will go away, go see your GP.

Testicular Cancer: Symptoms, Self-Examination, Diagnosis, Treatment and Prognosis

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One of the most curable cancers in men

A lump in the testicle can be frightening, particularly because testicular cancer often occurs in younger men. The reassuring news is that testicular cancer is one of the most successfully treated solid cancers.

When detected early, cure rates approach 100%. Even when the cancer has spread to lymph nodes, lungs or other parts of the body, modern chemotherapy and surgery can still cure many men.

The most important message is therefore:

Know what is normal for you, and if something changes, have it checked.

Most testicular lumps are not cancer, but a new lump, enlargement, hardness or persistent change in a testicle deserves medical assessment and usually an ultrasound.

The importance of checking your testicles

There is no population screening program for testicular cancer in Australia.

This makes testicular awareness particularly important.

Cancer Council Australia recommends that men become familiar with the normal shape, size and feel of their testicles and seek medical attention if they notice a lump, swelling, heaviness, aching or another change.

This is slightly different from recommending a rigid population-wide screening program. There is currently insufficient evidence that formal scheduled self-examination reduces mortality from testicular cancer.

Nevertheless, knowing your own anatomy makes sense.

How do I check my testicles?

A convenient time is during or after a warm shower or bath when the scrotal skin is relaxed.

Gently examine one testicle at a time between your fingers and thumb.

Become familiar with:

  • The usual size of each testicle
  • Its shape
  • Its firmness
  • The fact that one testicle commonly hangs slightly lower
  • The epididymis, which feels like a soft cord-like structure behind the testicle

You are not searching for microscopic abnormalities. You are simply learning what is normal for you.

Seek medical advice if you discover:

  • A new hard lump
  • Enlargement of one testicle
  • A change in shape
  • Increasing firmness
  • Persistent swelling
  • A heavy or dragging sensation
  • Persistent testicular discomfort
  • An unexplained difference from how the testicle normally feels

How often?

There is some variation between international recommendations.

The NHS in the United Kingdom advises checking the testicles regularly, approximately monthly, whereas Cancer Research UK emphasises awareness of what is normal rather than insisting upon a rigid monthly examination schedule.

In Australia, the practical message is best described as testicular awareness: become familiar with your testicles and investigate a persistent change rather than waiting to see whether it disappears.

Men at increased risk, including those with a previous undescended testicle, previous testicular cancer or significant family history, should discuss their individual surveillance with their doctor.

What is testicular cancer?

Approximately 90–95% of primary testicular cancers are germ-cell tumours.

They are divided into two broad groups:

Seminoma

Seminoma tends to behave in a relatively predictable manner and is extremely sensitive to both chemotherapy and radiotherapy.

Non-seminomatous germ-cell tumour (NSGCT)

This group includes:

  • Embryonal carcinoma
  • Yolk sac tumour
  • Choriocarcinoma
  • Teratoma
  • Mixed germ-cell tumours

A tumour containing both seminoma and non-seminomatous components is treated as a non-seminomatous germ-cell tumour.

An important clinical rule is:

Pure seminoma should not produce AFP.

If AFP is significantly elevated, the tumour is managed clinically as a non-seminomatous germ-cell cancer even if seminoma is reported in the pathological specimen.

Other testicular tumours

Less common tumours include:

Leydig cell tumours

Most are benign, although malignant variants occur.

Sertoli cell tumours

Again, most are benign but malignant variants are recognised.

Testicular lymphoma

Lymphoma becomes particularly important in older men and is managed quite differently from conventional germ-cell cancer.

Occasionally another cancer can metastasise to the testicle.

How does testicular cancer present?

The classic presentation is a:

Painless testicular lump

A man may notice:

  • Enlargement of one testicle
  • A hard area
  • A new lump
  • Alteration in shape
  • Increasing firmness
  • Scrotal heaviness

Testicular cancer can also cause discomfort or pain.

Therefore:

Pain does not rule cancer in, and absence of pain does not rule cancer out.

Symptoms of more advanced disease

When cancer has spread beyond the testicle, symptoms can include:

  • Back pain
  • Abdominal discomfort
  • Persistent cough
  • Shortness of breath
  • Chest symptoms
  • Enlarged lymph nodes
  • Weight loss
  • Fatigue
  • Breast tenderness or enlargement

Back pain can result from enlarged retroperitoneal lymph nodes behind the abdominal organs.

Diagnosis in Australia

The Australian diagnostic pathway is broadly consistent with European and British practice.

Step 1: Examination

Both testicles should be examined.

The abdomen and lymph-node regions may also be assessed.

Step 2: Testicular ultrasound

A high-resolution scrotal ultrasound with Doppler assessment is usually the first imaging investigation.

It determines whether a lesion is:

  • Within the testicle
  • Outside the testicle
  • Solid
  • Cystic
  • Vascular
  • Potentially malignant

A solid intratesticular mass should generally be considered malignant until proven otherwise.

Step 3: Tumour markers

Blood should ideally be collected before orchidectomy for:

AFP, Alpha-fetoprotein

May be elevated with:

  • Yolk sac tumour
  • Embryonal carcinoma
  • Mixed germ-cell tumours

β-hCG, Beta human chorionic gonadotropin

Can be elevated in:

  • Choriocarcinoma
  • Embryonal carcinoma
  • Mixed germ-cell tumours
  • Some seminomas

LDH, Lactate dehydrogenase

LDH is less specific but provides information regarding tumour burden and prognosis.

Importantly:

Normal tumour markers do not exclude testicular cancer.

Markers are repeated after orchidectomy because the rate at which AFP and β-hCG fall provides valuable information regarding whether active cancer remains elsewhere.

Step 4: Staging

Staging commonly involves CT imaging of the:

  • Chest
  • Abdomen
  • Pelvis

The retroperitoneal lymph nodes are particularly important because they represent the characteristic first lymphatic landing zone for many testicular cancers.

MRI can be used in selected circumstances.

PET scanning is not routinely recommended for initial staging.

FDG-PET has a specialised role after chemotherapy in selected patients with seminoma and a persistent residual mass.

Should the testicular lump be biopsied?

Usually no.

A needle biopsy through the scrotum is generally avoided when a germ-cell malignancy is suspected.

The standard procedure is:

Radical inguinal orchidectomy

The testicle and spermatic cord are removed through an incision in the groin.

This provides both treatment of the primary tumour and the tissue required for an accurate pathological diagnosis.

Fertility before treatment

This is particularly important because many patients are diagnosed while young.

The possibility of sperm banking should be discussed before chemotherapy, radiotherapy or other treatments that may impair fertility.

Ideally this conversation begins at diagnosis rather than after treatment has started.

One healthy remaining testicle will usually produce adequate testosterone and sperm, but some men with testicular cancer already have impaired sperm production before treatment.

Management of testicular cancer in Australia

Australian treatment is generally delivered through a multidisciplinary cancer team involving:

  • Urologists
  • Medical oncologists
  • Radiation oncologists
  • Radiologists
  • Pathologists
  • Fertility specialists when required

Complex metastatic, recurrent and post-chemotherapy disease is particularly suited to treatment through centres experienced in germ-cell cancer.

Australian practice broadly follows international evidence-based principles and is closely aligned with European and British practice, while incorporating Australian multidisciplinary cancer-care pathways.

Stage I seminoma

After radical inguinal orchidectomy, approximately 80% of men with unselected Stage I seminoma are cured by surgery alone.

For most reliable patients:

Active surveillance is generally preferred

This avoids exposing the majority of men who have already been cured to unnecessary chemotherapy or radiotherapy.

Surveillance involves scheduled:

  • Clinical review
  • Imaging
  • Tumour markers where appropriate

If recurrence occurs, treatment is usually extremely successful.

Adjuvant carboplatin

A single cycle of carboplatin may be considered for selected patients who prefer adjuvant treatment or for whom surveillance is unsuitable.

Radiotherapy

Radiotherapy is extremely effective against seminoma but is now used much less frequently for Stage I disease because of concern regarding long-term:

  • Secondary malignancies
  • Cardiovascular effects
  • Other radiation-related complications

Thus, in contemporary Australian practice, routine adjuvant radiotherapy for uncomplicated Stage I seminoma has largely moved into the background.

Stage I non-seminomatous germ-cell cancer

Approximately 70% of patients overall are cured by orchidectomy alone.

Management is influenced particularly by the presence or absence of lymphovascular invasion – LVI.

Without lymphovascular invasion

Surveillance is generally preferred for a reliable patient who is able to comply with follow-up.

With lymphovascular invasion

The risk of recurrence is considerably greater.

Options include:

  • Surveillance
  • One cycle of BEP chemotherapy

BEP consists of:

Bleomycin
Etoposide
Platinum – cisplatin

The advantages of avoiding unnecessary chemotherapy must be balanced against the increased likelihood of requiring several cycles of chemotherapy if metastatic recurrence subsequently occurs.

Retroperitoneal lymph-node dissection, RPLND

RPLND involves removal of lymph nodes from the retroperitoneum at the back of the abdomen.

It has an important but selective role.

In contemporary European and Australian-style practice, RPLND may be considered particularly for:

  • Selected marker-negative Stage II NSGCT
  • Residual masses after chemotherapy
  • Teratoma
  • Selected recurrent disease
  • Particular patients in whom chemotherapy is undesirable

Modern nerve-sparing RPLND attempts to preserve the sympathetic nerves responsible for normal antegrade ejaculation.

These procedures should ideally be performed in experienced high-volume centres.

Stage II seminoma

For limited Stage IIA or IIB seminoma, treatment options can include:

  • Radiotherapy
  • Cisplatin-based chemotherapy
  • In highly selected cases, specialist nerve-sparing RPLND

The precise choice depends upon lymph-node size, disease distribution, patient factors and the potential long-term consequences of each treatment.

For more extensive Stage IIB and Stage IIC disease, chemotherapy becomes increasingly favoured.

Metastatic seminoma and non-seminoma

Cisplatin-based combination chemotherapy transformed testicular cancer from a frequently fatal metastatic disease into one of the most curable metastatic solid cancers.

Common treatment includes:

BEP

Bleomycin + etoposide + cisplatin.

Depending upon the IGCCCG prognostic classification, treatment commonly consists of three or four cycles.

EP

Etoposide + cisplatin can be used in selected good-prognosis patients when bleomycin is unsuitable.

VIP

Etoposide + ifosfamide + cisplatin has a role in selected circumstances.

Surgery after chemotherapy

Surgery can remain crucial even after successful chemotherapy.

This is particularly important in non-seminomatous germ-cell cancer.

If tumour markers normalise but a residual retroperitoneal mass remains, surgery may reveal:

  • Fibrosis or necrosis
  • Mature teratoma
  • Persistent viable cancer

Teratoma is particularly important because it can be relatively resistant to chemotherapy and radiotherapy.

The EAU recommends surgical resection of visible residual NSGCT masses greater than 1 cm when serum tumour markers are normal or normalising.

What about immunotherapy?

Immunotherapy has revolutionised treatment for several urological cancers.

Unfortunately, germ-cell cancer has not followed the same script.

Checkpoint inhibitors targeting PD-1, PD-L1 and related pathways have been investigated in chemotherapy-resistant germ-cell tumours, but responses have generally been disappointing.

Therefore:

Immunotherapy is not standard first-line treatment for conventional seminoma or NSGCT in Australia, Europe, Britain or the United States.

Its role is currently largely confined to highly selected refractory disease and clinical trials.

European, British, Australian and American guidelines – are they different?

The reassuring answer is:

The major principles are remarkably similar.

All emphasise:

  1. Prompt ultrasound of a suspicious testicular mass
  2. AFP, β-hCG and LDH assessment
  3. Radical inguinal orchidectomy
  4. Appropriate CT staging
  5. Histological distinction between seminoma and non-seminoma
  6. Fertility discussion and sperm banking
  7. Surveillance for many Stage I cancers
  8. Cisplatin-based chemotherapy for metastatic germ-cell cancer
  9. Specialist surgery for appropriate residual or retroperitoneal disease

There are, however, some interesting differences in emphasis.

European approach: EAU

The European Association of Urology guidelines strongly favour avoiding unnecessary treatment.

For Stage I seminoma, surveillance is preferred when the patient can comply with follow-up.

Routine adjuvant radiotherapy is not recommended.

For Stage I NSGCT, the EAU uses lymphovascular invasion prominently for risk-adapted counselling:

  • LVI negative → surveillance generally preferred
  • LVI positive → surveillance or one cycle of BEP

Primary RPLND has a relatively limited role in Stage I NSGCT.

For marker-negative Stage IIA NSGCT, however, the 2026 EAU guideline supports nerve-sparing RPLND in an experienced specialised centre.

British approach

British practice is broadly similar to European practice.

The NHS pathway centres around:

Ultrasound → tumour markers → inguinal orchidectomy → staging → multidisciplinary oncology review.

Surveillance is commonly used following orchidectomy for appropriate Stage I disease.

Carboplatin remains an option for Stage I seminoma, while BEP chemotherapy is used for appropriate non-seminomatous and metastatic disease.

Radiotherapy retains a role predominantly in selected seminoma rather than non-seminomatous cancer.

British cancer services place considerable emphasis on:

  • Specialist germ-cell cancer multidisciplinary teams
  • Fertility preservation
  • Long-term follow-up
  • Minimising unnecessary treatment toxicity

This is very similar to contemporary Australian practice.

How does the American approach differ?

American management follows the same oncological principles, but the American Urological Association – AUA – gives RPLND somewhat greater prominence as an acceptable primary treatment option in selected early-stage disease.

For Stage IA NSGCT, the AUA recommends surveillance but recognises:

  • RPLND
  • One cycle of BEP

as alternatives for appropriate patients who decline surveillance or may not comply reliably.

For Stage IB NSGCT, American guidance recognises:

  • Surveillance
  • RPLND
  • One or two cycles of BEP

as options following shared decision-making.

This differs subtly from the EAU approach, where primary RPLND in Stage I NSGCT has a considerably narrower role.

Another evolving difference: RPLND for Stage II seminoma

Traditionally seminoma involving retroperitoneal lymph nodes was treated with either:

Radiotherapy or chemotherapy.

American guidelines have increasingly recognised primary RPLND as an option for carefully selected Stage IIA/IIB seminoma with limited retroperitoneal disease, particularly for patients wishing to avoid the potential long-term toxicity of chemotherapy or radiotherapy.

European recommendations are also evolving in this direction.

The 2026 EAU guideline now incorporates nerve-sparing RPLND and newer de-escalation strategies into the management discussion for selected Stage IIA/B seminoma.

This is an excellent example of why testicular cancer management continues to evolve.

Australia: where do we sit?

Australian practice sits comfortably between these international approaches.

For most Australian patients:

Stage I seminoma

Surveillance is generally preferred, with carboplatin available for selected patients.

Stage I NSGCT without LVI

Surveillance is generally preferred.

Stage I NSGCT with LVI

Surveillance or one cycle of BEP following individualised discussion.

Stage II seminoma

Radiotherapy or cisplatin-based chemotherapy depending upon disease volume, with increasingly selective consideration of surgical strategies in specialist centres.

Marker-positive metastatic disease

Cisplatin-based chemotherapy according to IGCCCG prognostic classification.

Residual NSGCT after chemotherapy

Surgical resection when indicated, ideally through an experienced germ-cell cancer service.

Australian cancer care increasingly emphasises multidisciplinary decision-making and treatment that achieves cure while reducing unnecessary long-term toxicity.

Why avoiding unnecessary treatment matters

A 25-year-old cured of testicular cancer may live another 60 years.

That changes the treatment equation.

The question is no longer simply:

“Which treatment will cure the cancer?”

It is also:

“Which treatment will cure this cancer while leaving the smallest possible footprint over the next several decades?”

This is why surveillance has become so important.

Chemotherapy and radiotherapy are extraordinarily effective, but they should be used when their benefit justifies their immediate and long-term risks.

Prognosis

The prognosis for testicular cancer is excellent.

Stage I disease has survival approaching 100%.

Even metastatic disease is frequently curable.

Prognosis depends upon:

  • Seminoma versus non-seminoma
  • Stage
  • Tumour-marker levels
  • Sites of metastatic disease
  • Response to chemotherapy
  • Tumour-marker decline
  • Presence of residual disease
  • Ability to completely resect appropriate residual masses

Importantly, doctors genuinely use the word cure when discussing metastatic testicular cancer.

After treatment: don’t forget the other testicle

Having had one testicular cancer increases the risk of developing cancer in the remaining testicle.

Men should therefore remain familiar with the remaining testicle and report any new abnormality promptly.

Long-term survivorship care may also address:

  • Testosterone levels
  • Fertility
  • Cardiovascular health
  • Kidney function
  • Hearing
  • Peripheral neuropathy
  • Lung health following bleomycin
  • Psychological wellbeing
  • Sexual health
  • Risk of late treatment complications

The take-home message

Testicular cancer tends to arrive at an inconvenient age, when most men are thinking about careers, relationships, families and weekend plans rather than cancer.

Fortunately, it is also one of medicine’s most impressive cancer success stories.

Know your testicles.

Become familiar with what is normal for you.

Don’t ignore a change.

A lump, enlargement, hardness, heaviness or persistent discomfort deserves examination.

Don’t be embarrassed.

Your urologist has quite literally made a career out of discussing these things.

And don’t assume a diagnosis of testicular cancer means the worst.

With modern surveillance, surgery, chemotherapy and selective radiotherapy, the overwhelming majority of men diagnosed with testicular cancer can expect to be cured.

Robotic-Assisted Radical Prostatectomy: When Is a Non-Nerve-Sparing Procedure Necessary?

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Removing the prostate while putting cancer control first

Robotic-assisted radical prostatectomy is a well-established surgical treatment for localised and selected locally advanced prostate cancer. During the operation, the prostate gland and seminal vesicles are removed, and the bladder is reconnected to the urethra. In selected patients, pelvic lymph nodes may also be removed.

One of the important decisions made before and during prostate cancer surgery is whether the nerves responsible for erections can safely be preserved.

This is known as nerve-sparing prostatectomy.

Unfortunately, nerve preservation is not always appropriate. When prostate cancer is close to, involves, or is suspected of extending beyond the outer edge of the prostate near these nerves, attempting to preserve them may compromise the completeness of cancer removal.

In this situation, a partial or complete non-nerve-sparing robotic prostatectomy may be recommended.

The guiding principle is simple:

Preserve the nerves when it is oncologically safe to do so, but do not preserve them at the expense of adequately treating the prostate cancer.

What are the nerves that are being “spared”?

Running immediately alongside the prostate are delicate bundles of nerves and blood vessels known collectively as the neurovascular bundles.

These structures contain nerves that play an important role in producing erections.

They sit extremely close to the outer surface, or capsule, of the prostate. This anatomical relationship creates a challenge during prostate cancer surgery.

If the cancer is safely contained within the prostate and sufficiently distant from the neurovascular bundle, the surgeon may be able to carefully dissect the prostate away while preserving the nerves.

This is a nerve-sparing radical prostatectomy.

If cancer is suspected to extend towards or through the prostate capsule in this area, the surgeon may need to remove some or all of the neurovascular tissue together with the prostate.

This is a non-nerve-sparing prostatectomy.

Why would a surgeon deliberately remove the erectile nerves?

It may initially seem counterintuitive to remove structures that are so important for sexual function.

The reason is cancer control.

The primary purpose of radical prostatectomy is to completely remove the prostate cancer.

If a tumour is growing very close to the edge of the prostate, particularly next to a neurovascular bundle, dissecting too close to the prostate in an attempt to preserve the nerves could potentially leave cancer cells behind.

This is called a positive surgical margin.

In appropriately selected patients, taking a wider margin around the prostate may therefore provide a safer cancer operation.

The decision represents a balance between:

Cancer control

and

preservation of erectile function.

When these two goals conflict, cancer control generally takes priority.

When may a non-nerve-sparing prostatectomy be recommended?

Non-nerve-sparing surgery may be considered when there is a significant risk that prostate cancer has extended towards or into the tissues surrounding the prostate.

Examples include:

Locally advanced prostate cancer

A tumour suspected of extending through the prostate capsule, particularly clinical T3 disease, may require a wider surgical excision.

Cancer close to the neurovascular bundle on MRI

Modern multiparametric prostate MRI can provide valuable information about the location of the tumour and its relationship to the prostate capsule and neurovascular bundles.

Features suggesting extraprostatic extension may influence the decision not to preserve the nerve bundle on that side.

High-grade prostate cancer

Higher-grade cancers, including cancers with an unfavourable Gleason score or ISUP Grade Group, may have a greater likelihood of extending outside the prostate.

The biopsy result alone does not automatically determine whether the nerves can be preserved, but it forms part of the overall assessment.

Extensive cancer on prostate biopsy

Large-volume disease, particularly when concentrated along the outer portion of the prostate near a neurovascular bundle, may make nerve preservation less appropriate.

Very high PSA or other high-risk features

PSA level, PSA density, biopsy findings, MRI appearance and clinical examination are considered together when estimating the likelihood of disease extending beyond the prostate.

Cancer involving one particular side of the prostate

Importantly, nerve sparing does not necessarily have to be “all or nothing.”

If the cancer is predominantly on one side, it may sometimes be possible to preserve the neurovascular bundle on the opposite side.

This is known as unilateral nerve sparing.

Nerve sparing is not simply YES or NO

Modern robotic prostate surgery is more nuanced than dividing operations into completely nerve-sparing and completely non-nerve-sparing procedures.

Depending on the location and extent of the cancer, surgery may involve:

  • Bilateral nerve sparing
  • Unilateral nerve sparing
  • Partial nerve sparing
  • Wider excision on one side and nerve preservation on the other
  • Complete bilateral non-nerve-sparing surgery

The surgical plan can therefore be tailored to the individual patient and, importantly, to the cancer on each side of the prostate.

How does nerve-sparing surgery differ from non-nerve-sparing surgery?

During nerve-sparing surgery, the surgeon carefully separates the neurovascular bundle from the surface of the prostate while attempting to minimise traction, heat and other potential injury to these delicate nerves.

During non-nerve-sparing surgery, the dissection is deliberately performed further away from the prostate.

The neurovascular tissue is removed together with the prostate where necessary to obtain a wider cancer margin.

The robotic platform provides magnified three-dimensional vision and highly controlled instrument movement. This allows the surgeon to identify tissue planes with considerable precision.

However, robotic technology cannot make an unsafe nerve-sparing operation safe.

The biology and location of the cancer ultimately determine how close to the prostate the surgeon can safely operate.

What happens to erections after non-nerve-sparing prostatectomy?

This is one of the most important issues to discuss before surgery.

The nerves surrounding the prostate are responsible for signalling increased blood flow into the penis to produce a natural erection.

If both neurovascular bundles are completely removed, the likelihood of recovering spontaneous erections adequate for sexual intercourse is very low.

This is different from nerve-sparing surgery, where the nerves remain anatomically intact but may temporarily function poorly following surgery.

After nerve-sparing prostatectomy, erectile recovery can occur gradually over many months and sometimes over 18–24 months or longer.

After complete bilateral non-nerve-sparing surgery, however, the nerves themselves have been removed rather than temporarily stunned.

The expectations for recovery are therefore very different.

Does non-nerve-sparing surgery affect sensation or orgasm?

This is an important distinction.

The nerves responsible for penile sensation are different from the neurovascular nerves primarily responsible for erections.

Many men can therefore continue to experience penile sensation and sexual pleasure following radical prostatectomy.

Orgasm may also remain possible.

However, radical prostatectomy removes the prostate and seminal vesicles and disconnects the reproductive pathway. Consequently, there is no ejaculation of semen after surgery.

This is sometimes described as a dry orgasm.

The sensation of orgasm can also feel different after prostate surgery.

Does non-nerve-sparing prostatectomy cause infertility?

Yes.

Radical prostatectomy results in permanent infertility because the prostate and seminal vesicles are removed and sperm can no longer enter the ejaculate.

Men who may wish to father children in the future should discuss sperm banking before surgery.

This applies whether the operation is nerve sparing or non-nerve sparing.

Is a non-nerve-sparing procedure reversible?

No.

Once a neurovascular bundle has been surgically removed, it cannot simply be reattached at a later date.

This is an important difference between temporary nerve dysfunction and actual nerve removal.

After nerve-sparing surgery, the nerves may be anatomically preserved but temporarily injured or “stunned”. Recovery may therefore occur with time.

After complete non-nerve-sparing surgery, the erectile nerves have been physically removed as part of the cancer operation.

The procedure itself is therefore not reversible.

However, this does not mean that erections or sexual activity are impossible.

There are several effective treatments available for erectile dysfunction following prostatectomy.

Can erections still be achieved after non-nerve-sparing surgery?

Rarely yes, but they will usually require assistance.

Treatment options include:

PDE5 inhibitor tablets

Medications such as sildenafil or tadalafil are commonly used after prostate surgery.

They rely substantially on functioning nerve pathways and are therefore generally more effective following nerve-sparing surgery.

Their effectiveness following complete bilateral non-nerve-sparing surgery is considerably more limited.

Vacuum erection device

A vacuum erection device creates negative pressure around the penis, drawing blood into the erectile tissues.

A constriction ring can then be placed around the base of the penis to maintain the erection.

Because this technique does not depend on intact erectile nerves, it can be useful after non-nerve-sparing surgery.

Penile injection therapy

Medication can be injected directly into the erectile tissue of the penis.

These medications act directly on penile blood vessels and therefore do not require normal prostate-associated nerve signalling.

For this reason, penile injections can be highly effective even after bilateral non-nerve-sparing prostatectomy.

Penile prosthesis

For men with persistent erectile dysfunction who wish to restore reliable erections, a penile prosthesis can provide an effective long-term solution.

An inflatable penile prosthesis allows an erection to be mechanically produced when desired.

For appropriately selected men, satisfaction rates following penile prosthesis surgery are generally high.

What about penile rehabilitation?

Penile rehabilitation may be discussed following radical prostatectomy.

The objectives can include maintaining penile tissue health, encouraging regular oxygenation of the erectile tissues, minimising shortening and fibrosis, and assisting the return to sexual activity.

A rehabilitation program may involve:

  • PDE5 inhibitor medication where appropriate
  • Vacuum erection therapy
  • Penile injection therapy
  • Regular sexual stimulation
  • Early assessment and management of erectile dysfunction

The appropriate program depends heavily on whether surgery was bilateral nerve sparing, unilateral nerve sparing or completely non-nerve sparing.

It is therefore important that expectations are realistic.

After complete bilateral nerve removal, rehabilitation cannot make the removed nerves grow back. Instead, treatment focuses on maintaining penile health and providing alternative ways of achieving an erection.

Can the surgeon decide during the operation whether to spare the nerves?

Sometimes.

The intended degree of nerve sparing is usually planned before surgery using information from:

  • Prostate MRI
  • Prostate biopsy
  • PSA
  • Clinical examination
  • Location and volume of cancer
  • Gleason score and ISUP Grade Group
  • Estimated risk of extraprostatic extension
  • The patient’s existing erectile function
  • The patient’s priorities regarding cancer control and sexual function

However, the final surgical approach may occasionally need to be modified according to findings encountered during the operation.

The most important objective remains adequate removal of the cancer.

Does non-nerve-sparing surgery improve cancer cure rates?

Not every patient benefits from wider surgery.

For men with cancer safely confined within the prostate, unnecessary removal of the neurovascular bundles may produce significant functional consequences without providing additional cancer benefit.

Conversely, when cancer is suspected of extending close to or beyond the prostate capsule adjacent to a neurovascular bundle, wider excision may reduce the risk of leaving tumour at the surgical margin.

This is why the decision must be individualised.

The best operation is not automatically the operation that preserves the most nerves. It is the operation that provides appropriate cancer clearance while preserving as much normal function as can safely be preserved.

What about urinary continence?

Nerve sparing primarily relates to erectile function, rather than the urinary sphincter responsible for continence.

Urinary control after radical prostatectomy depends on several factors including:

  • Age
  • Pre-operative urinary function
  • Pelvic floor strength
  • Urethral length
  • Bladder function
  • Surgical anatomy and technique
  • Previous prostate treatments
  • Individual healing

Pelvic floor rehabilitation before and after surgery can be an important part of recovery.

Non-nerve-sparing surgery does not automatically mean that a patient will remain incontinent.

Questions worth asking before surgery

If a non-nerve-sparing robotic prostatectomy has been recommended, useful questions to discuss with your urologist include:

Why is nerve preservation considered unsafe in my particular cancer?

Is the concern on one side or both sides of the prostate?

Could unilateral or partial nerve sparing be considered?

What does my MRI show about the relationship between the cancer and neurovascular bundles?

What is my estimated chance of erectile recovery with the proposed operation?

What erectile rehabilitation options will be available after surgery?

Should I consider sperm banking before treatment?

These conversations are particularly important because the decision to remove a neurovascular bundle is generally irreversible.

The important message

A non-nerve-sparing robotic-assisted radical prostatectomy is not an inferior version of nerve-sparing surgery.

In the right patient, it is a deliberate cancer-control strategy.

When prostate cancer is close to or suspected of involving the tissues surrounding the prostate, preserving the erectile nerves too aggressively may risk leaving cancer behind.

Modern robotic surgery allows the operation to be tailored to the individual patient. Some men can undergo bilateral nerve preservation, others may benefit from preservation on only one side, while patients with more extensive disease may require a wider non-nerve-sparing excision.

The consequences for erectile function are important and should be understood before surgery.

Once the neurovascular nerves have been removed, the procedure cannot be reversed.

However, loss of spontaneous erections does not mean the end of sexual intimacy. Vacuum devices, penile injection therapy and penile prostheses can provide effective options when natural erections are no longer possible.

Ultimately, the aim is to achieve the best possible balance between two important goals:

Effective treatment of the prostate cancer and preservation of quality of life.

A note for patients

Every prostate cancer is different. MRI findings, biopsy results, PSA, cancer grade, age, general health, pre-existing erectile function and personal priorities all influence the appropriate surgical approach.

A detailed discussion with your urologist before robotic prostatectomy is essential so that you understand whether nerve sparing is appropriate, what degree of nerve preservation may be possible and what this means for cancer control, continence and sexual function.

This information is intended for general patient education and does not replace individual medical advice. Treatment recommendations should be based on your individual prostate cancer characteristics, imaging, pathology, general health and discussion with your treating urologist.

Understanding Overactive Bladder: Symptoms, Assessment and Treatment Options

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Overactive bladder can make everyday life feel organised around the nearest toilet. Shopping, travelling, exercise, sleep and social activities may all be affected by sudden urgency, frequent urination or leakage.

It is common, but it is not simply an inevitable part of ageing. Symptoms deserve assessment because several bladder, urinary and medical conditions can produce a similar pattern.

This article explains overactive bladder as a condition and outlines the broad approaches used to investigate and manage it. It does not recommend a particular medicine, device or brand.

What is overactive bladder?

Overactive bladder (OAB) is a symptom syndrome characterised by urinary urgency, a sudden, compelling need to pass urine that is difficult to defer. It is usually accompanied by increased frequency during the day and waking at night to urinate, with or without urgency urinary incontinence.

Possible symptoms include:

  • a sudden need to urinate that is difficult to postpone
  • passing urine more frequently than expected
  • waking repeatedly at night to urinate
  • leaking urine before reaching the toilet
  • restricting travel or activities because of toilet access
  • using pads because of unpredictable urgency

OAB is a clinical diagnosis. Some people demonstrate involuntary bladder contractions, known as detrusor overactivity, during urodynamic testing; others with typical symptoms do not.

What causes the symptoms?

The bladder normally stores urine at low pressure and empties when it is convenient. OAB symptoms arise when the sensation or control of bladder filling becomes abnormal. The cause is not always identifiable.

Factors that can cause or aggravate similar symptoms include:

  • urinary tract infection
  • excessive caffeine, alcohol or fluid intake
  • medicines such as diuretics
  • constipation
  • poorly controlled diabetes
  • bladder stones
  • incomplete bladder emptying
  • bladder outlet obstruction
  • pelvic floor dysfunction
  • genitourinary syndrome of menopause
  • neurological conditions
  • reduced mobility or difficulty reaching a toilet
  • sleep disorders or fluid redistribution causing nocturia

Visible blood in the urine, recurrent infection, pelvic pain, difficulty passing urine or rapidly changing symptoms require further assessment rather than an assumption that OAB is the cause.

Overactive bladder in men

Urgency and frequency in men may occur alone or together with bladder outlet obstruction from prostate enlargement, urethral narrowing or impaired bladder contraction.

An assessment may therefore include the urinary stream, prostate, urinary flow and the amount of urine remaining after voiding. Treating urgency without recognising significant obstruction or incomplete emptying may worsen retention in some patients.

Overactive bladder after menopause

After menopause, reduced oestrogen can contribute to vaginal dryness, irritation, recurrent urinary infection, urgency and discomfort. These changes are often grouped under the term genitourinary syndrome of menopause.

Identifying vaginal or urinary tract changes is important because management may differ from treatment for isolated OAB. Any hormonal treatment requires an individual discussion of suitability, expected benefit, uncertainty and risk.

How is OAB assessed?

Assessment begins with listening to the pattern and impact of the symptoms. Depending on the individual, it may include:

  • a medical, urinary and medication history
  • examination
  • urinalysis or urine culture
  • a bladder diary
  • review of fluid, caffeine and alcohol intake
  • assessment of bowel function
  • measurement of urinary flow
  • ultrasound measurement of post-void residual urine
  • kidney-function or glucose testing when clinically indicated
  • assessment for pelvic organ prolapse or prostate enlargement

A bladder diary records the timing and volume of drinks, urination, urgency and leakage. It can help distinguish OAB from excessive urine production, nocturnal polyuria or habitual frequent voiding.

Are urodynamic studies always required?

No. Many patients with uncomplicated symptoms can begin conservative treatment without urodynamics.

Urodynamic testing may be helpful when the diagnosis is uncertain, bladder emptying is poor, previous treatment has failed, neurological dysfunction is suspected, or an invasive treatment is being considered. The test should answer a specific clinical question rather than be performed routinely.

When might cystoscopy or imaging be needed?

Cystoscopy or urinary tract imaging is not automatically required for uncomplicated OAB. It may be considered when there is blood in the urine, recurrent infection, pain, suspected stones, previous pelvic surgery, obstruction or another concerning feature.

First steps in management

Conservative treatment is often the starting point and may be used alone or with other therapies.

Bladder training

Bladder training aims to increase the interval between toilet visits and reduce the habit of urinating “just in case.” A planned program may involve:

  • recording voiding patterns
  • gradually extending the interval between voids
  • using distraction, breathing or pelvic floor contractions when urgency occurs
  • avoiding rushing to the toilet where it is safe to pause

Progress is usually gradual. An unrealistic schedule can lead to frustration or increased leakage.

Pelvic floor rehabilitation

Pelvic floor exercises may help suppress urgency and improve continence. Correct technique matters; repeatedly contracting the wrong muscles or performing excessive exercises may be unhelpful. Assessment by a pelvic floor physiotherapist can be useful.

Fluids and bladder irritants

Reducing excessive caffeine or alcohol may improve symptoms. Large volumes of fluid over a short period can also provoke urgency.

Fluid should not be restricted excessively. Concentrated urine may irritate the bladder and inadequate intake can contribute to constipation, infection or dehydration. Advice should reflect medical conditions, climate and activity.

Constipation, weight and mobility

Treating constipation may reduce pressure on the bladder. Weight reduction can improve urinary symptoms for some people. Mobility aids, clear access to the toilet and suitable clothing can reduce functional leakage even when bladder symptoms persist.

Managing nocturia

Waking at night to urinate is not always caused by OAB. Other contributors include sleep apnoea, leg swelling, heart or kidney disease, evening fluid intake and medicines.

Management should be directed at the cause. Moving a diuretic to a different time, for example, should occur only on advice from the prescribing clinician.

Where do prescription medicines fit?

Prescription medicines may be discussed when conservative measures have not provided sufficient relief, when symptoms are particularly troublesome, or when a combined approach is appropriate.

Two broad medicine classes are commonly used:

  1. Antimuscarinic medicines, which reduce muscarinic stimulation of the bladder.
  2. Beta-3 adrenergic agonists, which promote bladder relaxation during filling.

These medicines are not suitable for everyone. The choice should follow an individual assessment of symptoms, bladder emptying, other medical conditions, current medicines and personal priorities.

Antimuscarinic medicines

This class may reduce urgency, frequency and urgency incontinence in some patients. Possible adverse effects include:

  • dry mouth
  • constipation
  • blurred vision or dry eyes
  • dizziness or drowsiness
  • difficulty emptying the bladder
  • urinary retention
  • confusion or cognitive effects, particularly in susceptible older people

Caution may be required in people with impaired bladder emptying, certain forms of glaucoma, severe constipation or gastrointestinal motility disorders, cognitive impairment, or a high total anticholinergic burden.

Anticholinergic burden and cognition

Many medicines used for conditions other than OAB also have anticholinergic effects. The combined burden may contribute to dry mouth, constipation, sedation, falls, confusion and loss of function.

Observational research has found associations between prolonged exposure to medicines with strong anticholinergic effects and cognitive decline or dementia. An association does not prove that a particular medicine caused dementia in an individual patient, but the overall medication burden deserves review—especially in older people or those with cognitive concerns.

Beta-3 adrenergic agonists

This class acts differently and generally produces fewer classic anticholinergic effects. Possible adverse effects can include:

  • increased blood pressure
  • headache
  • palpitations or faster heart rate
  • urinary tract infection
  • difficulty emptying the bladder
  • medicine interactions

Blood pressure, cardiovascular history, kidney or liver function, bladder emptying and interacting medicines may influence suitability. Current Australian Product Information should guide prescribing and monitoring.

Can medicine classes be combined?

Combination therapy may be considered after a partial response to a single medicine, but additional benefit must be weighed against increased adverse effects, interactions and cost.

In men with both storage symptoms and possible bladder outlet obstruction, treatment may also need to address the obstructive component. A urinary flow test and post-void residual measurement may help guide the decision.

How is a medicine trial reviewed?

A medicine trial should have a clear purpose and review point. Reassessment may consider:

  • urgency episodes
  • daytime and night-time frequency
  • leakage and pad use
  • bladder diary findings
  • quality of life
  • blood pressure where relevant
  • constipation, dry mouth, cognition or other adverse effects
  • urinary flow and residual urine in patients at risk of retention

If there is little benefit or unacceptable harm, the diagnosis and management plan should be reconsidered. Increasing or continuing treatment indefinitely is not automatically appropriate.

Patients should not start, stop or change a prescription medicine without advice from their prescriber.

What if conservative care and medicines are insufficient?

Persistent symptoms do not mean that no further options exist. Reassessment is important before an invasive treatment to confirm the likely cause and identify incomplete emptying, obstruction or another condition.

Depending on the patient, options may include:

Intravesical botulinum toxin treatment

A prescription medicine can be injected into the bladder wall through a cystoscope to reduce involuntary bladder contractions. Some patients experience reduced urgency and leakage, but benefit varies and is temporary.

Important risks include urinary tract infection, increased residual urine and inability to empty the bladder adequately. Some patients require temporary intermittent self-catheterisation. Treatment must be selected and administered by an appropriately qualified clinician.

Tibial nerve stimulation

Electrical stimulation near the ankle can influence the nerve pathways involved in bladder control. Treatment protocols vary, and repeated sessions may be required. Response is variable.

Sacral neuromodulation

Sacral neuromodulation uses an implanted system to stimulate nerves involved in bladder and pelvic-floor control. It may be considered for selected patients after assessment and usually involves a test phase. Potential disadvantages include an operation, device-related complications, later revision and ongoing follow-up.

These treatments differ in invasiveness, risks, durability, repeat-treatment requirements, availability and cost. None is the best choice for every patient.

When should medical advice be sought promptly?

Prompt assessment is appropriate for:

  • inability to pass urine
  • visible blood in the urine
  • fever, flank pain or systemic illness with urinary symptoms
  • recurrent urinary infections
  • new leg weakness, numbness or loss of bowel control
  • significant pelvic or bladder pain
  • rapidly worsening symptoms
  • new incontinence accompanied by neurological symptoms

Urgent or emergency care may be required when symptoms are severe.

Questions to discuss with a clinician

  • Are my symptoms most consistent with OAB, or could there be another cause?
  • Am I emptying my bladder adequately?
  • Which conservative measures are most relevant to me?
  • What are the reasonable treatment options, including no immediate treatment?
  • What benefit might I realistically expect?
  • Which adverse effects or interactions matter with my other conditions and medicines?
  • How and when will treatment be reviewed?
  • Would further testing change management?
  • What symptoms should prompt urgent assessment?

The bottom line

Overactive bladder is a symptom syndrome, not a single test result. Assessment should look for infection, excessive urine production, incomplete emptying, obstruction, menopause-related changes, neurological disease and other contributors.

Management usually begins with education, bladder training, pelvic floor rehabilitation and attention to fluids, caffeine, constipation and related medical problems. Prescription medicine may be one part of treatment after an individual assessment, but benefits vary and adverse effects matter.

When symptoms remain troublesome, further evaluation and carefully selected minimally invasive treatments may be considered. The aim is not simply to prescribe another tablet; it is to understand the cause, reduce symptoms safely and improve daily life.

This article provides general disease education and does not replace individual medical advice. It does not promote or recommend a particular prescription medicine, therapeutic product, device or brand. Treatment decisions should be made with an appropriately qualified health professional after assessment of the individual patient.

References and further reading

Publication note

This draft is structured as general disease education for an Australian public-facing website. It should not be accompanied by branded medicine or device imagery, product pricing, supply information, testimonials, inducements, superiority claims, or wording that encourages a reader to request a named therapeutic good. Review the page title, search metadata, images, links, social-media caption and nearby booking prompts together, because the overall context determines whether material may be regarded as advertising.

Upper Tract Urothelial Carcinoma

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Cancer of the Renal Pelvis and Ureter

Urothelial carcinoma is most commonly associated with the bladder, but the same specialised lining extends all the way from the bladder up the ureters and into the collecting system of each kidney.

When a urothelial cancer develops in the renal pelvis or ureter, it is called upper tract urothelial carcinoma (UTUC).

UTUC is considerably less common than bladder cancer. Importantly, its behaviour varies enormously. Some tumours are small, superficial and relatively slow growing, while others are aggressive cancers capable of invading the kidney, surrounding tissues, lymph nodes and distant organs.

The key to successful management is therefore not simply finding the tumour, but determining how aggressive it is and how likely it is to spread.

What Is the Upper Urinary Tract?

Urine produced by the kidney drains through:

Kidney → renal calyces → renal pelvis → ureter → bladder → urethra

The inner surface of the renal pelvis, ureter and bladder is covered by urothelium, previously called transitional epithelium.

Cancer arising from these cells is called urothelial carcinoma.

UTUC can therefore occur in:

  • the renal pelvis;
  • one or more renal calyces;
  • the upper, middle or lower ureter;
  • multiple areas of the same urinary tract; or
  • occasionally both upper urinary tracts.

Patients with UTUC may also develop urothelial tumours within the bladder, either at the same time or later.

What Causes Upper Tract Urothelial Cancer?

Cancer develops when genetic damage accumulates within urothelial cells, allowing them to grow and divide abnormally.

Frequently there is no single identifiable cause, but several important risk factors are recognised.

Smoking

Cigarette smoking is one of the most important preventable risk factors for urothelial carcinoma.

Carcinogenic chemicals absorbed through the lungs enter the bloodstream, are filtered by the kidneys and become concentrated in the urine. The urothelium may therefore be exposed to these substances for many years.

Stopping smoking remains important even after diagnosis because of its wider health benefits and potential relevance to future urothelial cancer risk.

Previous bladder cancer

Patients who have previously had urothelial carcinoma of the bladder have an increased risk of developing urothelial carcinoma elsewhere within the urinary tract.

Similarly, patients treated for UTUC remain at risk of subsequently developing bladder cancer.

Occupational chemical exposure

Long-term exposure to certain industrial chemicals, particularly some aromatic amines historically associated with dye, rubber, textile, leather and chemical industries, has been associated with urothelial cancer.

Lynch syndrome

A small but important proportion of UTUC occurs in people with Lynch syndrome, an inherited disorder caused by abnormalities in DNA mismatch-repair genes.

UTUC, particularly in a younger patient or someone with a strong family history of bowel, endometrial or other Lynch-associated cancers, may prompt consideration of genetic assessment.

Chronic inflammation

Long-standing urinary tract inflammation and some chronic infections may contribute to malignant change. Chronic stone disease has particularly been associated with squamous carcinoma of the renal pelvis, which is a different and much less common tumour type.

Previous analgesic exposure

Heavy historical exposure to certain analgesics, particularly phenacetin-containing preparations that are no longer routinely used in many countries, has been associated with upper tract urothelial malignancy.

What Are the Symptoms?

Blood in the urine

The most common warning sign is:

Haematuria: blood in the urine

This may be obvious, turning the urine pink, red or occasionally dark brown.

Importantly, haematuria may:

  • occur only once;
  • disappear for weeks or months;
  • be completely painless; or
  • only be detected microscopically on a urine test.

Visible blood in the urine should always be appropriately investigated, particularly in adults.

Do not assume that painless bleeding is simply due to infection, prostate enlargement or a blood-thinning medication without appropriate assessment.

Flank or loin pain

A tumour can obstruct drainage of urine from the kidney.

This may produce:

  • persistent flank discomfort;
  • loin pain;
  • renal colic;
  • hydronephrosis, where the kidney becomes dilated because urine cannot drain normally.

Blood clots passing down the ureter can occasionally produce severe colicky pain resembling a kidney stone.

Recurrent urinary symptoms

Some patients experience:

  • urinary frequency;
  • urgency;
  • burning when passing urine;
  • recurrent apparent urinary tract infections.

These symptoms are much more commonly caused by benign conditions, but persistent or unexplained symptoms may warrant further investigation.

General symptoms

More advanced disease can occasionally cause:

  • unexplained weight loss;
  • loss of appetite;
  • fatigue;
  • persistent pain;
  • anaemia.

Fortunately, many tumours are detected before these symptoms develop.

How Is UTUC Diagnosed?

Investigation usually involves several complementary tests.

1. Urine testing

Urine is assessed for:

  • microscopic blood;
  • infection;
  • renal abnormalities; and
  • sometimes malignant cells.

Urine cytology

Urine cytology examines shed urinary cells under a microscope.

It is particularly useful for detecting high-grade urothelial carcinoma, although a negative cytology result does not completely exclude cancer.

Selective urine samples may sometimes be collected directly from the affected upper urinary tract.

2. CT Urography

CT urography is one of the most important imaging investigations for suspected UTUC.

Contrast-enhanced CT imaging allows assessment of:

  • the kidneys;
  • renal collecting systems;
  • ureters;
  • bladder;
  • lymph nodes; and
  • surrounding organs.

A tumour may appear as a filling defect, thickening of the ureter or renal pelvis, or an infiltrating mass.

CT can also identify obstruction and hydronephrosis.

3. Cystoscopy

Because urothelial cancer can occur at more than one location, the bladder should generally also be examined.

A flexible cystoscope is passed through the urethra into the bladder to look for associated bladder tumours.

Ureteroscopy and Biopsy

Sometimes imaging alone cannot provide enough information about the tumour.

A ureteroscope is a very fine telescope passed through the urethra and bladder and then into the ureter and renal collecting system.

This allows the urologist to directly inspect the tumour.

During ureteroscopy it may be possible to:

  • identify the location of the tumour;
  • assess whether there is one tumour or several;
  • estimate its size;
  • obtain selective urine cytology;
  • take a biopsy; and
  • in selected low-risk tumours, treat the lesion with a laser.

Biopsy is particularly helpful in determining whether the tumour is low-grade or high-grade.

An important limitation is that ureteroscopic biopsy samples are small, so determining the exact depth of invasion before definitive surgery can sometimes be difficult.

Low-Risk Versus High-Risk Disease

Modern management increasingly divides UTUC according to its risk of invasion and progression.

Factors considered include:

  • tumour grade;
  • appearance on CT;
  • tumour size;
  • number of tumours;
  • presence of hydronephrosis;
  • urine cytology;
  • ureteroscopic appearance;
  • biopsy findings;
  • evidence of invasion; and
  • previous urothelial cancer.

This distinction is extremely important because treatment can range from relatively conservative endoscopic therapy to removal of the entire kidney and ureter.

Treatment of Low-Risk UTUC

Selected patients with low-risk disease may be suitable for kidney-sparing treatment.

The objective is to control the cancer while preserving as much functioning kidney tissue as possible.

Ureteroscopic Laser Treatment

A ureteroscope is passed to the tumour and the lesion is treated using laser energy.

Laser treatment can:

  • vaporise;
  • coagulate; or
  • fragment the tumour.

Modern flexible ureteroscopes allow access to much of the renal collecting system.

Advantages

Kidney-sparing treatment may:

  • preserve kidney function;
  • avoid major abdominal surgery;
  • reduce recovery time;
  • be particularly valuable in patients with impaired kidney function or a solitary kidney.

Disadvantages

The trade-off is the need for very careful surveillance.

UTUC has a tendency to recur, so patients may require repeated:

  • ureteroscopy;
  • urine cytology;
  • CT imaging; and
  • occasionally further laser treatments or biopsies.

Kidney preservation therefore does not mean that the tumour can simply be treated once and forgotten.

Segmental Ureterectomy

Some tumours confined to a relatively short section of ureter can be treated by removing only the affected portion.

This is known as segmental ureterectomy.

It is particularly useful for appropriately selected tumours of the distal ureter.

The affected segment is removed and the remaining ureter is either reconnected or reimplanted into the bladder.

This can preserve the kidney while providing a complete surgical specimen for pathological examination.

Treatment of High-Risk UTUC

For patients with high-risk localised disease, the standard definitive operation is generally:

Radical Nephroureterectomy

This involves removal of:

the kidney + entire ureter + a cuff of bladder surrounding the ureteric opening

Removing the complete ureter is important because leaving part of the affected ureter behind may allow cancer to recur within the remaining urothelium.

The procedure can often be performed using:

  • robotic surgery;
  • laparoscopic surgery; or
  • occasionally open surgery.

The choice depends upon tumour characteristics, anatomy, previous surgery and individual circumstances.

What About the Lymph Nodes?

For selected high-risk tumours, lymph nodes draining the affected area may also be removed.

A lymph-node dissection can provide important staging information and may be incorporated into the surgical management of appropriately selected high-risk disease.

Chemotherapy

Systemic chemotherapy plays an important role in selected patients with higher-risk UTUC.

Platinum-based chemotherapy, particularly cisplatin-containing treatment, has traditionally formed an important part of systemic treatment.

Chemotherapy may be given:

Before surgery: neoadjuvant chemotherapy

One potential advantage is that both kidneys are still present, and renal function may therefore be better able to tolerate cisplatin.

After surgery: adjuvant chemotherapy

Chemotherapy may be recommended after nephroureterectomy when the final pathology demonstrates sufficiently high-risk disease.

An important consideration is that removing a kidney can reduce renal function, potentially affecting the patient’s ability to receive certain chemotherapy drugs.

Treatment decisions are therefore ideally made by a multidisciplinary uro-oncology team.

Immunotherapy and Newer Treatments

The treatment of advanced urothelial carcinoma has changed considerably in recent years.

Depending upon the stage, previous treatment and molecular characteristics of the cancer, systemic therapy may include combinations of:

  • platinum-based chemotherapy;
  • immune checkpoint inhibitors;
  • antibody-drug conjugates; and
  • targeted treatments for selected molecular abnormalities such as FGFR alterations.

These treatments are particularly relevant to patients with locally advanced, recurrent or metastatic disease.

Treatment is increasingly individualised according to the biological characteristics of the tumour and the patient’s kidney function and overall health.

Treatment Placed Directly Into the Upper Urinary Tract

For carefully selected non-invasive disease, medication may sometimes be delivered directly into the renal pelvis and ureter.

Options can include topical chemotherapy or immunotherapy in selected circumstances.

A chemoablative gel formulation of mitomycin has also been developed for selected low-grade UTUC, allowing prolonged contact between chemotherapy and the tumour.

These treatments are specialised and are not suitable for every patient.

What Happens After Treatment?

Follow-up is particularly important because urothelial carcinoma has a characteristic ability to develop at another point along the urinary tract.

After treatment, surveillance may include:

  • cystoscopy;
  • urine cytology;
  • CT urography or other upper-tract imaging;
  • blood tests to assess kidney function;
  • ureteroscopy following kidney-sparing treatment.

The exact surveillance schedule depends upon whether the original tumour was low or high risk and what treatment was performed.

Can the Cancer Return in the Bladder?

Yes.

One of the distinctive features of UTUC is the significant risk of subsequently developing urothelial carcinoma within the bladder.

Published data have reported subsequent bladder tumours in a substantial proportion of patients following treatment of UTUC.

For this reason, regular cystoscopic surveillance remains important even when the original kidney or ureteric tumour has been completely removed.

What Is the Prognosis?

The outlook for UTUC depends predominantly upon:

  • tumour stage;
  • tumour grade;
  • lymph-node involvement;
  • metastatic spread;
  • tumour multifocality;
  • response to treatment; and
  • certain pathological and molecular characteristics.

The most important question is whether the cancer remains superficial or has invaded deeply through the wall of the renal pelvis or ureter.

Superficial, localised disease

The outlook can be excellent when a tumour is identified while still superficial and confined to the upper urinary tract. The National Cancer Institute reports that more than 90% of superficial cancers confined to the renal pelvis or ureter may be curable.

Invasive disease

Once a tumour has invaded deeply into the wall or surrounding tissues, the risk of lymph-node involvement and distant spread increases substantially.

High-grade and invasive tumours therefore usually require more aggressive treatment and closer surveillance.

Metastatic disease

When UTUC has spread to distant organs, treatment is generally systemic rather than surgical alone.

Although metastatic UTUC remains a serious disease, modern systemic treatments have expanded considerably and can provide meaningful cancer control for selected patients.

UTUC and Kidney Function

Preserving kidney function is an important part of treatment planning.

Removing one kidney is usually well tolerated when the opposite kidney is healthy, but kidney function can become particularly important in patients with:

  • pre-existing chronic kidney disease;
  • diabetes;
  • hypertension;
  • a solitary kidney;
  • bilateral upper-tract tumours; or
  • conditions likely to affect future kidney function.

The decision between kidney-sparing treatment and radical nephroureterectomy therefore involves balancing two priorities:

adequate cancer control and preservation of renal function.

Cancer safety remains the priority, but in appropriately selected low-risk disease these objectives can often coexist.

When Should You See a Urologist?

Seek medical assessment if you develop:

  • visible blood in the urine;
  • persistent microscopic haematuria;
  • unexplained flank or loin pain;
  • recurrent unexplained urinary symptoms;
  • abnormal findings on kidney imaging; or
  • haematuria with a previous history of urothelial cancer.

Blood in the urine should not automatically be attributed to prostate enlargement, infection, kidney stones or blood-thinning medication without appropriate investigation.

The Bottom Line

Upper tract urothelial carcinoma is an uncommon cancer arising from the lining of the renal pelvis or ureter.

Blood in the urine is its most important warning sign.

Investigation commonly involves CT urography, cystoscopy, urine cytology and, when required, ureteroscopy with biopsy.

Treatment is increasingly tailored to the biological risk of the tumour.

Small, low-grade tumours may sometimes be managed with kidney-sparing ureteroscopic laser treatment or segmental surgery, while high-risk invasive cancers generally require radical nephroureterectomy with removal of the bladder cuff, sometimes combined with lymph-node surgery and systemic treatment.

Long-term surveillance is essential because urothelial cancer can recur elsewhere within the urinary tract, particularly the bladder.

The reassuring part is that when UTUC is detected while still superficial and localised, the likelihood of successful treatment can be very high.

A Note for Patients

Every upper tract urothelial tumour is different. Treatment depends upon the tumour’s location, size, grade, stage, number of lesions, kidney function and your general health.

Management should therefore be individualised following discussion with your urologist and, for higher-risk disease, a multidisciplinary uro-oncology team.

This information is intended for general patient education and should not replace individual medical advice, examination or treatment recommendations from your treating specialist.

The current 2026 EAU guideline specifically incorporates updated risk stratification, kidney-sparing management, bladder-cuff and lymph-node considerations, systemic therapy, and follow-up recommendations.

Kidney Stones: Understanding the Different Types of Renal Calculi and Their Treatment

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Kidney stones, medically known as renal calculi or nephrolithiasis, are solid crystalline deposits that develop within the kidneys. Although we tend to talk about “a kidney stone” as if all stones are the same, there are several distinctly different types.

Knowing the composition of a kidney stone matters. Different stones have different causes, appearances, recurrence risks and, importantly, different strategies for prevention and treatment.

Modern management therefore involves more than simply removing the stone. The aim is to answer three questions:

What is the stone? Why did it form? And how can we prevent the next one?

What Are Kidney Stones Made Of?

The major types of urinary stones are:

  1. Calcium oxalate stones
  2. Calcium phosphate stones
  3. Uric acid stones
  4. Struvite or infection stones
  5. Cystine stones
  6. Rare metabolic and medication-related stones

Stones are not always chemically pure. Many contain a mixture of different crystalline components.

The European Association of Urology recommends reliable stone analysis and a basic metabolic evaluation in stone-forming patients, with more detailed metabolic investigation particularly important in patients at high risk of recurrence.

1. Calcium Oxalate Stones

The most common kidney stone

Calcium oxalate stones are the most frequently encountered urinary calculi.

They may consist predominantly of:

  • Calcium oxalate monohydrate, known as whewellite
  • Calcium oxalate dihydrate, known as weddellite

Calcium oxalate monohydrate stones can be particularly hard and resistant to fragmentation with shockwave lithotripsy.

Why do calcium oxalate stones form?

Contributing factors may include:

  • Low urine volume or dehydration
  • Excess urinary calcium
  • Excess urinary oxalate
  • Low urinary citrate
  • High dietary sodium intake
  • Excessive animal protein intake
  • Certain bowel diseases or previous intestinal surgery
  • Genetic predisposition
  • Metabolic abnormalities

Importantly, calcium stones do not necessarily mean that a patient is eating too much calcium.

Severely restricting normal dietary calcium can actually be counterproductive because calcium within the intestine binds oxalate and reduces its absorption.

Management

Small asymptomatic stones may sometimes simply be monitored.

When treatment is required, options include:

  • Shockwave lithotripsy (SWL)
  • Flexible ureteroscopy and laser lithotripsy
  • Percutaneous nephrolithotomy (PCNL)
  • Observation in appropriately selected patients

Prevention depends on the underlying metabolic abnormality and may include increased fluid intake, dietary modification, reduction in excessive sodium intake, potassium citrate for selected patients, thiazide therapy for hypercalciuria and treatment of hyperoxaluria or hyperuricosuria when identified.

2. Calcium Phosphate Stones

Calcium phosphate stones are less common than calcium oxalate stones.

They may contain:

  • Hydroxyapatite
  • Carbonate apatite
  • Brushite

Why do they form?

Calcium phosphate crystallisation is favoured by relatively alkaline urine.

They may be associated with:

  • Hypercalciuria
  • Renal tubular acidosis
  • Hyperparathyroidism
  • Urinary tract abnormalities
  • Certain metabolic disorders

Brushite stones deserve particular attention. They can be extremely hard and may respond poorly to shockwave treatment.

Management therefore needs to consider not only stone size and location, but also stone density and previous stone composition.

3. Uric Acid Stones

Uric acid stones behave very differently from calcium stones.

They are strongly associated with persistently acidic urine and may occur in patients with:

  • Gout
  • Metabolic syndrome
  • Diabetes
  • Obesity
  • High purine intake
  • High animal-protein intake
  • Chronic dehydration
  • Excessive uric acid production or excretion

Uric acid stones account for approximately 10% of renal stones and all uric acid stone formers are considered at increased risk of recurrence.

Why are uric acid stones special?

Because unlike most kidney stones, uric acid stones can potentially be dissolved.

Treatment involves increasing urinary pH, usually using an alkalinising medication such as potassium citrate.

For active oral dissolution therapy, urinary pH needs to be carefully monitored. Current EAU guidance describes targeting approximately pH 7.0–7.2 during chemolysis, while avoiding excessive alkalinisation because this may encourage calcium phosphate crystallisation.

This creates one of the happier conversations in stone management:

“You have a kidney stone, but we may be able to make it disappear without an operation.”

Not every uric acid stone will dissolve successfully, and obstructed or infected kidneys require separate and sometimes urgent treatment.

4. Struvite Stones: The Infection Stones

Struvite stones contain magnesium ammonium phosphate and are closely associated with urinary infections caused by certain urease-producing bacteria.

These bacteria change the chemistry of the urine, producing an alkaline environment favourable for rapid stone formation.

Struvite stones can become very large and occasionally form a branching staghorn calculus, occupying much of the kidney’s collecting system.

Why are these stones important?

The stone and infection can maintain one another.

Leaving significant infected stone material behind may therefore contribute to:

  • Recurrent urinary infection
  • Rapid stone regrowth
  • Kidney damage
  • Sepsis

Management generally involves treating the infection and achieving as complete a stone clearance as reasonably possible. Large stones frequently require PCNL, sometimes performed in more than one stage.

Infection stone formers are regarded as being at high risk of recurrence.

5. Cystine Stones

Cystine stones are uncommon and are caused by cystinuria, an inherited disorder affecting the transport of certain amino acids through the kidneys.

Cystine is relatively insoluble in urine and can crystallise to form stones.

These patients may start developing stones at a young age and can experience repeated stone episodes throughout life.

Treatment and prevention

Prevention is particularly important and may involve:

  • Very high fluid intake
  • Reduced dietary sodium
  • Urinary alkalinisation
  • Potassium citrate
  • Specialist medication such as tiopronin in selected recurrent cases

Current EAU guidance recommends aiming for a urine volume greater than 3 litres per day in adults with cystinuria and maintaining urinary pH above approximately 7.5 to improve cystine solubility.

Cystine stones are also relatively hard, which can make shockwave treatment less successful. Ureteroscopy with laser treatment or PCNL may therefore be required depending on stone burden.

6. Rare Kidney Stones

Much less commonly, stones may consist of substances such as:

  • Xanthine
  • 2,8-dihydroxyadenine
  • Ammonium urate
  • Matrix material
  • Medication-related crystalline material

These stones can sometimes provide the first clue to an underlying metabolic, genetic or medication-related disorder.

Recurrent unusual stones therefore deserve specialist investigation rather than simply repeated stone removal.

How Do Kidney Stones Present?

Some kidney stones sit quietly within the kidney and are discovered incidentally during an ultrasound or CT scan.

Others announce their arrival with considerably less subtlety.

A stone entering and obstructing the ureter may cause renal colic, producing severe pain from the loin toward the abdomen or groin.

Other symptoms can include:

  • Blood in the urine
  • Nausea and vomiting
  • Urinary urgency or frequency
  • Burning during urination
  • Recurrent urinary infection
  • Fever or chills
  • Intermittent loin discomfort

Fever plus an obstructed kidney is an emergency

An infected obstructed urinary system can progress rapidly to urosepsis.

Urgent drainage with a ureteric stent or nephrostomy tube, together with appropriate antibiotics and supportive treatment, may be required. Definitive stone treatment is generally delayed until the infection has been controlled.

How Are Kidney Stones Investigated?

CT Scan

A non-contrast CT scan of the kidneys, ureters and bladder provides detailed information regarding:

  • Stone size
  • Number of stones
  • Exact location
  • Degree of obstruction
  • Kidney anatomy
  • Stone density measured in Hounsfield units

CT density may also provide clues about stone composition and the likelihood of successful shockwave fragmentation.

Ultrasound

Ultrasound avoids radiation and is particularly useful for:

  • Surveillance
  • Detecting hydronephrosis
  • Monitoring known renal stones
  • Selected younger patients
  • Pregnancy

However, very small stones and ureteric stones can sometimes be difficult to identify accurately.

Plain X-ray

A KUB X-ray may be useful for monitoring certain radiopaque stones.

Calcium-containing stones are usually radiopaque, whereas uric acid stones are typically radiolucent on plain X-ray.

Do All Kidney Stones Need Treatment?

No.

A small, non-obstructing and asymptomatic kidney stone may sometimes be monitored with periodic imaging.

Treatment becomes more appropriate when there is:

  • Stone growth
  • Recurrent pain
  • Haematuria
  • Urinary obstruction
  • Recurrent infection
  • Declining renal function
  • Significant stone burden
  • High risk of future complications
  • Occupational or travel considerations
  • Patient preference

These factors are reflected in contemporary EAU recommendations.

Treatment Options for Kidney Stones

1. Active Surveillance

Small asymptomatic renal stones can sometimes be observed.

Follow-up may include ultrasound, X-ray or CT depending on the type, size and visibility of the stone.

The advantage is obvious: no procedure unless one becomes necessary.

The disadvantage is equally obvious: stones have not signed a contract promising to remain where they are.

They may enlarge, migrate into the ureter, cause obstruction or become symptomatic.

2. Shockwave Lithotripsy

Extracorporeal shockwave lithotripsy (SWL) uses externally generated shockwaves focused onto the stone.

The aim is to fragment the calculus into smaller pieces that can subsequently pass through the urinary tract.

Advantages

  • Non-invasive
  • Usually rapid recovery
  • No incision
  • Useful for appropriately selected renal stones

Limitations

Success depends on:

  • Stone size
  • Location
  • Density
  • Composition
  • Skin-to-stone distance
  • Renal anatomy

Hard stones such as calcium oxalate monohydrate, brushite and cystine stones may be less responsive.

More than one treatment session may be required.

3. Flexible Ureteroscopy and Laser Lithotripsy

A fine flexible telescope is passed through the urethra and bladder, up the ureter and into the kidney.

There are no external incisions.

The stone can then be fragmented or dusted using a laser, with larger fragments removed using tiny retrieval baskets.

Advantages

  • Minimally invasive
  • High stone clearance rates for appropriately selected stones
  • Can treat stones resistant to shockwave therapy
  • Allows direct visualisation
  • Suitable for many locations within the kidney

Possible disadvantages

  • Requires anaesthesia
  • Temporary ureteric stenting may be required
  • Stent discomfort
  • Bleeding or infection
  • Ureteric injury is uncommon but possible
  • Occasionally a second procedure is required

4. Percutaneous Nephrolithotomy

PCNL involves creating a small tract through the skin directly into the kidney.

It is particularly useful for:

  • Large renal calculi
  • Staghorn stones
  • Complex stones
  • Large-volume infection stones
  • Stones unlikely to respond adequately to less invasive techniques

Current EAU guidance recommends PCNL as the first-line treatment for renal stones larger than 2 cm in most suitable patients.

PCNL generally provides excellent clearance of large stone burdens but is more invasive than ureteroscopy or shockwave treatment.

Potential complications include bleeding, infection, injury to surrounding structures and the need for additional procedures.

5. Dissolution Therapy

This option is mainly relevant to uric acid stones.

Urinary alkalinisation can gradually dissolve the stone, potentially avoiding surgery.

Treatment requires:

  • Correct identification or strong suspicion of uric acid composition
  • Regular urine pH monitoring
  • Appropriate alkalinising medication
  • Follow-up imaging
  • Patient compliance

It is important not to assume that every radiolucent stone is uric acid, and treatment should be supervised appropriately.

Choosing the Right Treatment

There is no single “best” kidney stone operation.

The appropriate treatment depends on a combination of:

Stone factors

  • Size
  • Number
  • Location
  • Composition
  • Density
  • Previous growth

Kidney factors

  • Anatomy
  • Obstruction
  • Infection
  • Renal function

Patient factors

  • Symptoms
  • Medical conditions
  • Anticoagulant therapy
  • Previous stone procedures
  • Occupation
  • Travel requirements
  • Personal preference

Two patients with apparently similar 10 mm stones may therefore receive quite different recommendations.

Preventing the Next Kidney Stone

Removing a stone solves today’s problem.

Preventing another stone solves tomorrow’s problem.

Patients with recurrent stones, multiple stones, bilateral stones, unusual stone composition, young age at presentation or other high-risk features may benefit from metabolic investigation.

This may include blood testing and 24-hour urine collections assessing factors such as:

  • Urine volume
  • Calcium
  • Oxalate
  • Citrate
  • Uric acid
  • Sodium
  • Magnesium
  • Urinary pH

Stone analysis is particularly valuable whenever a stone can be retrieved. Current EAU guidance recommends reliable stone analysis and basic metabolic evaluation for stone formers, with specific metabolic assessment for high-risk patients.

General Kidney Stone Prevention

Although prevention should ultimately be tailored to stone composition, several principles apply to many stone formers.

Drink more water

Maintaining generous urine output dilutes the substances responsible for crystal formation.

Water remains wonderfully unexciting and remarkably effective.

Reduce excessive salt intake

High sodium intake can increase urinary calcium excretion and contribute to calcium stone formation.

Maintain normal dietary calcium

Patients with calcium stones should not automatically eliminate calcium-containing foods.

A balanced dietary calcium intake may actually reduce intestinal oxalate absorption.

Moderate excessive animal protein

Large amounts of meat and other purine-rich foods may contribute to increased urinary uric acid and more acidic urine in susceptible individuals.

Maintain a healthy weight

Obesity and metabolic syndrome are particularly associated with uric acid stone formation.

Investigate recurrent stones

Repeatedly removing stones without investigating why they keep forming can become a rather expensive game of geological whack-a-mole.

Can Medication Prevent Kidney Stones?

Yes, in appropriately selected patients.

Depending on the metabolic abnormality and stone composition, preventive medication may include:

  • Potassium citrate
  • Thiazide or thiazide-like medication
  • Allopurinol
  • Urinary alkalinising therapy
  • Tiopronin for selected cystinuria patients

Medication should ideally be guided by stone analysis, blood investigations and, when indicated, 24-hour urine testing rather than prescribed indiscriminately.

The Bottom Line

A kidney stone is not simply a kidney stone.

A calcium oxalate stone, uric acid stone, infection stone and cystine stone may look similar on a scan, but they can have very different causes and require very different long-term strategies.

Modern kidney stone management combines:

accurate imaging + appropriate stone removal + stone analysis + metabolic investigation + prevention.

Treatment may range from simple surveillance through to shockwave lithotripsy, flexible ureteroscopy and laser treatment, PCNL or, in selected uric acid stones, medical dissolution therapy.

The ultimate aim is not simply to leave the operating theatre stone-free.

It is to keep the patient stone-free.

When Should You See a Urologist?

Consider urological assessment if you have:

  • Recurrent kidney stones
  • Persistent loin or flank pain
  • Blood in the urine
  • Recurrent urinary infections
  • A stone associated with urinary obstruction
  • Increasing stone size on surveillance imaging
  • Multiple or bilateral kidney stones
  • A large renal calculus
  • Previous complex stone surgery

Severe pain associated with fever, chills or feeling systemically unwell requires urgent medical assessment, as an infected obstructed kidney can be a medical emergency.

This information is intended for general patient education and does not replace individual medical assessment. The appropriate investigation, surveillance and treatment of kidney stones should be tailored to the individual patient.

This blog is aligned with the current 2026 EAU Urolithiasis Guidelines, including the updated recommendations on stone composition, renal stone treatment and metabolic prevention.

EAU Guidelines on Urolithiasis

Calcium Oxalate Kidney Stones: Treatment, Surgery and Prevention

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Calcium oxalate stones are the most common type of urinary tract stone. Although the name may suggest that eating too much calcium is the problem, the biology is considerably more complicated. Stone formation reflects the interaction between urine volume, calcium, oxalate, citrate, sodium, dietary factors, genetics and, in some patients, underlying metabolic or gastrointestinal conditions.

The encouraging news is that most calcium oxalate stones can be treated effectively, and the risk of forming further stones can often be substantially reduced with appropriate investigation and prevention.

This guide explains conservative management, imaging, surgical treatment, ureteric pre-stenting, laser fragmentation, recovery and long-term prevention.

What is a calcium oxalate stone?

Calcium oxalate crystals form when urine becomes sufficiently concentrated with calcium and oxalate for crystals to develop and grow.

Two principal forms occur:

  • Calcium oxalate monohydrate, which tends to be harder and more resistant to shock-wave fragmentation.
  • Calcium oxalate dihydrate, which is generally more readily fragmented.

Importantly, calcium oxalate stones cannot usually be dissolved with medication. This differs from uric acid stones, which can sometimes be dissolved by alkalinising the urine.

Treatment therefore involves either allowing a suitable stone to pass naturally, monitoring an asymptomatic stone, or physically removing or fragmenting it when intervention is required.

How do calcium oxalate stones present?

A stone sitting quietly inside the kidney may produce no symptoms at all and may be discovered incidentally during imaging performed for another reason.

When a stone moves into the ureter, symptoms can be dramatic and may include:

  • Severe loin or flank pain
  • Pain radiating towards the groin or testicle/labia
  • Nausea and vomiting
  • Blood in the urine
  • Urinary frequency or urgency
  • Burning with urination
  • Restlessness during an episode of renal colic

Fever or chills associated with an obstructing stone require urgent medical assessment. An infected obstructed kidney is a urological emergency and may require immediate drainage with a ureteric stent or nephrostomy rather than definitive stone treatment at that time.

Imaging calcium oxalate stones

CT scan

A non-contrast CT of the kidneys, ureters and bladder (CT KUB) is generally the most accurate investigation for suspected urinary tract calculi.

CT provides valuable information about:

  • Stone size
  • Exact location
  • Number of stones
  • Degree of urinary obstruction
  • Hydronephrosis
  • Stone density
  • Anatomy relevant to treatment planning

Stone density is measured in Hounsfield units (HU) and can sometimes help predict how readily a stone may fragment with shock-wave treatment.

The major disadvantage of CT is radiation exposure, although modern low-dose CT protocols can substantially reduce the radiation dose.

Ultrasound

Ultrasound avoids radiation and is particularly useful for:

  • Follow-up
  • Monitoring known renal stones
  • Detecting hydronephrosis
  • Pregnancy
  • Patients requiring repeated imaging

Its disadvantage is that small ureteric stones can be missed, and measurement of stone size is generally less accurate than CT.

Plain X-ray – KUB

Most calcium oxalate stones are radiopaque and therefore visible on a plain abdominal X-ray.

KUB imaging can consequently be useful for monitoring selected stones, particularly following treatment or when considering shock-wave lithotripsy.

Does every calcium oxalate stone require surgery?

No.

A small stone without infection, significant obstruction or uncontrolled pain can frequently be managed conservatively.

Small asymptomatic stones within the kidney may also simply be monitored.

Observation is reasonable when the potential risks and inconvenience of treatment exceed the likely benefit.

Current European guidelines recognise active surveillance as an option for selected asymptomatic renal stones, although stone growth, development of symptoms or obstruction may eventually prompt intervention.

Conservative management

For a small ureteric stone that is likely to pass spontaneously, treatment may include:

Hydration

Maintain normal good hydration. Trying to “flush” a painful obstructing stone through by drinking enormous quantities of water is generally unnecessary and can actually worsen discomfort.

Pain relief

Anti-inflammatory medication is frequently particularly effective for renal colic, provided there are no medical contraindications.

Additional analgesia or anti-nausea medication may occasionally be required.

Medical expulsive therapy

An alpha-blocker such as tamsulosin may be prescribed in selected patients to facilitate passage of a ureteric stone.

The greatest benefit appears to occur with distal ureteric stones larger than approximately 5 mm, although its use for stone passage is off-label in many jurisdictions.

Straining the urine

Catching the stone is surprisingly useful. Sending a retrieved stone for laboratory analysis confirms its composition and helps direct prevention.

The small pebble that caused an astonishing amount of trouble can therefore become an important diagnostic specimen.

When should a stone be removed?

Intervention may be recommended when there is:

  • Persistent or recurrent pain
  • Failure of the stone to progress
  • Significant urinary obstruction
  • Deterioration in renal function
  • Recurrent urinary infection
  • Increasing stone size
  • A low likelihood of spontaneous passage
  • A large renal stone burden
  • Occupational or lifestyle reasons where an unpredictable episode of renal colic would be problematic

Treatment is individualised according to stone size, location, density, renal anatomy, symptoms and patient preference.

Surgical treatment options

1. Extracorporeal Shock-Wave Lithotripsy – ESWL/SWL

Shock-wave lithotripsy focuses externally generated shock waves onto the stone, breaking it into smaller fragments that can subsequently pass through the urinary tract.

Advantages

  • No incision
  • Usually relatively rapid recovery
  • May avoid ureteroscopy
  • Useful for appropriately selected renal and ureteric stones

Disadvantages

  • Not all calcium oxalate stones fragment equally well
  • Hard calcium oxalate monohydrate stones may be resistant
  • Several treatment sessions may be required
  • Fragments still need to pass down the ureter
  • Residual fragments can remain
  • Temporary renal colic can occur
  • Less effective for some lower-pole renal stones and larger stones

The success of SWL is strongly influenced by stone size, location, composition, patient anatomy and stone hardness.

2. Ureteroscopy and laser lithotripsy

Ureteroscopy has transformed modern stone treatment.

A fine telescope is passed through the natural urinary tract:

urethra → bladder → ureter → kidney

There is therefore no external surgical incision.

Rigid or semi-rigid ureteroscopy can be used for ureteric stones, while flexible ureteroscopy allows access to stones within the kidney.

Laser fragmentation

Once the stone is identified, laser energy is delivered through an extremely fine fibre passed through the ureteroscope.

Modern systems include:

  • Holmium laser
  • Thulium fibre laser (TFL)

Both are highly effective technologies for flexible ureteroscopic stone treatment, and contemporary European guidelines recommend Ho or TFL for ureteroscopic laser lithotripsy.

The stone can be treated using several strategies.

Fragmentation and extraction

The stone is divided into several pieces, which are removed using a small basket.

Dusting

The laser progressively converts the stone into extremely small particles or “dust”, allowing much of the material to pass spontaneously.

Pop-dusting or further fragmentation

Larger fragments can be further reduced until they are sufficiently small to pass or be extracted.

Advantages of ureteroscopy and laser treatment

Ureteroscopy provides:

  • Direct visualisation of the stone
  • High stone-clearance rates
  • Treatment of stones resistant to shock-wave lithotripsy
  • Access to most areas of the ureter and kidney
  • Immediate fragmentation
  • Ability to retrieve fragments for stone analysis
  • No external incision
  • Usually short hospitalisation

Compared with shock-wave lithotripsy, ureteroscopy generally offers a greater likelihood of becoming stone-free after a single procedure, although this comes at the price of greater invasiveness and a somewhat higher complication rate.

Possible complications of ureteroscopy

Although generally safe, complications can include:

  • Blood in the urine
  • Urinary infection
  • Pain
  • Ureteric swelling
  • Temporary difficulty passing urine
  • Residual stone fragments
  • Need for repeat ureteroscopy
  • Ureteric perforation
  • Ureteric stricture
  • Sepsis

Major ureteric injury is uncommon.

The EAU reports overall ureteroscopy complication rates of approximately 4–25%, with most complications being minor. Urosepsis is an important but uncommon serious complication.

Pre-operative urine testing and treatment of urinary infection are therefore important components of safe stone surgery.

What is pre-stenting?

A ureteric stent is a thin flexible tube extending from the kidney to the bladder.

Sometimes the ureter is too narrow to safely introduce the instruments required for flexible ureteroscopy.

Instead of forcing access, a temporary stent can be inserted.

The stent gently allows passive dilatation of the ureter before definitive surgery.

Ureteroscopy is then performed at a later date, commonly after the ureter has had time to accommodate the stent.

Does everyone need pre-stenting?

No.

Routine pre-stenting before ureteroscopy is not necessary.

However, pre-stenting can be useful when:

  • The ureter is particularly narrow
  • Previous access has been unsuccessful
  • A large renal stone burden is anticipated
  • An access sheath is likely to be required
  • Staged ureteroscopy is planned
  • Emergency drainage was previously required because of infection or obstruction

Evidence suggests that pre-stenting can improve access and may improve stone-free outcomes for renal stones, although the benefit is less clear for ureteric stones.

The price of this convenience is that the patient has to live temporarily with a ureteric stent.

Ureteric stent side effects

Stents are useful pieces of equipment, but they rarely win popularity contests.

Possible symptoms include:

  • Urinary frequency
  • Urgency
  • Bladder discomfort
  • Burning during urination
  • Blood in the urine
  • Flank discomfort during urination
  • Pelvic or groin discomfort

Symptoms disappear after the stent is removed.

Alpha-blocker medication can reduce stent-related symptoms in selected patients.

Is a stent required after laser treatment?

Not always.

After straightforward uncomplicated ureteroscopy with complete stone clearance and no ureteric trauma, a postoperative stent may not be necessary.

A stent is more likely to be placed following:

  • Difficult ureteric access
  • Significant ureteric swelling
  • Ureteric trauma
  • Large stone burden
  • Residual fragments
  • Bleeding
  • Infection concerns
  • Prolonged surgery
  • Staged treatment

Current evidence supports avoiding routine postoperative stenting following uncomplicated ureteroscopy.

3. Percutaneous nephrolithotomy – PCNL

Very large renal stones are usually better approached directly through the back rather than attempting to remove the entire stone burden through the ureter.

PCNL involves creating a small tract through the skin into the kidney, through which instruments can fragment and extract the stone.

PCNL remains the standard treatment for large renal calculi, particularly stones greater than approximately 2 cm and complex or staghorn stone burdens.

Advantages

  • Excellent clearance of large stone burdens
  • Large fragments can be removed directly
  • Often more efficient than multiple ureteroscopies for large stones

Disadvantages

  • More invasive
  • Bleeding risk
  • Infection/sepsis risk
  • Longer recovery than routine ureteroscopy
  • Potential need for nephrostomy drainage
  • Rare injury to surrounding structures

Recovery after ureteroscopy and laser lithotripsy

Most patients recover relatively quickly.

It is common to experience:

  • Mild burning when passing urine
  • Pink or blood-stained urine
  • Urinary frequency
  • Mild flank discomfort
  • Stent-related symptoms

Many patients return to light activities within several days, although recovery depends on the extent of the procedure and whether a stent remains.

Heavy physical activity may need to be avoided for a short period.

Patients should seek medical attention for:

  • Fever or chills
  • Increasing severe pain
  • Persistent vomiting
  • Inability to pass urine
  • Heavy persistent bleeding
  • Feeling systemically unwell

Have we finished once the stone has gone?

Not quite.

Removing a stone treats today’s stone.

Preventing another one requires identifying why it formed.

This distinction is important because calcium oxalate stone disease can recur.

Current EAU data suggest approximately 26% of first-time stone formers experience recurrence within five years, while a smaller group develops highly recurrent disease.

Patients with recurrent stones, multiple stones, bilateral stones, young-onset stone disease or particular metabolic risk factors deserve more detailed investigation.

Metabolic investigation

Depending on the clinical situation, evaluation may include:

Blood tests

  • Calcium
  • Creatinine and renal function
  • Electrolytes
  • Uric acid
  • Bicarbonate
  • Parathyroid hormone when indicated

Stone analysis

Any retrieved stone should ideally be sent for formal analysis.

24-hour urine collection

This can measure:

  • Total urine volume
  • Calcium
  • Oxalate
  • Citrate
  • Sodium
  • Uric acid
  • Urinary pH
  • Other relevant metabolic parameters

The results allow prevention to be targeted rather than relying on a generic “kidney stone diet”.

Preventing calcium oxalate stones

1. Drink more fluid

For many patients, the single most important intervention is increasing urine volume.

Rather than concentrating stone-forming chemicals into a small volume of urine, additional fluid keeps them diluted.

Water should generally form the majority of fluid intake.

The required intake varies with climate, exercise, occupation and perspiration. Someone working outdoors during an Australian summer may require considerably more fluid than someone sitting in an air-conditioned office.

2. Do not automatically restrict calcium

This is one of the most common misconceptions about calcium oxalate stones.

Calcium in the stone does not mean calcium should disappear from the diet.

Normal dietary calcium is generally desirable because calcium within the intestine binds dietary oxalate. This reduces oxalate absorption and consequently reduces the amount reaching the urine.

The EAU specifically advises that dietary calcium should generally not be restricted unless there is a particular reason to do so.

3. Reduce excessive salt intake

A high sodium intake increases urinary calcium excretion.

Reducing dietary salt can therefore help reduce urinary calcium and forms an important part of recurrence prevention.

Pay particular attention to hidden salt in:

  • Processed foods
  • Takeaway meals
  • Processed meats
  • Sauces
  • Packaged snacks
  • Some breads and prepared foods

4. What about oxalate?

Traditional advice often involved handing patients an intimidating list of foods containing oxalate.

Contemporary Australian CARI guidance takes a more nuanced approach and recommends against a blanket low-oxalate diet for calcium oxalate stone prevention. Instead, maintaining appropriate dietary calcium and addressing excessive intake in patients with hyperoxaluria may be more useful.

Patients with documented high urinary oxalate may need individualised dietary advice.

5. Avoid excessive vitamin C supplementation

Vitamin C can be metabolised to oxalate.

For recurrent calcium oxalate stone formers, particularly those with elevated urinary oxalate, very high-dose vitamin C supplements should generally be avoided unless there is a specific medical indication.

6. Moderate excessive animal protein

Large amounts of animal protein can alter urinary chemistry in ways that encourage stone formation, including reducing urinary citrate and increasing acid and uric acid loads.

The aim is generally moderation rather than elimination.

 

7. What about cola and other soft drinks?

Patients frequently ask whether cola-type soft drinks contribute to kidney stones.

The answer is more nuanced than simply blaming carbonation. The bubbles themselves are not the problem. Of greater relevance are the acid composition, sugar content and the fact that regular soft-drink consumption can displace water and other more favourable fluids from the diet.

Cola-type drinks

Many dark cola-style beverages contain phosphoric acid. High consumption of these beverages has been associated in some studies with an increased risk of stone formation or recurrence.

One clinical trial examining patients with recurrent stones found that reducing soft-drink consumption lowered recurrence, with the benefit appearing particularly relevant among people whose preferred beverages were acidified with phosphoric acid.

This does not mean that an occasional cola-type drink will automatically produce a kidney stone. The concern is frequent or high-volume consumption, particularly in someone already predisposed to recurrent stones.

Sugar-sweetened soft drinks

Regular consumption of sugar-sweetened beverages may also be undesirable for stone prevention.

Large amounts of sugar, particularly fructose-containing sweeteners, may alter urinary chemistry and have been associated with a greater risk of kidney stone formation in observational studies.

There is another very practical issue: every large glass of soft drink may be replacing a glass of water.

For a recurrent stone former, that is not an especially favourable trade.

Are sugar-free versions better?

Removing sugar eliminates one potential problem, but it does not necessarily make a cola-type beverage ideal for someone with recurrent stones.

Sugar-free varieties may still contain phosphoric acid, and frequent consumption may still replace water in the daily fluid intake.

What should I drink instead?

For most calcium oxalate stone formers:

Water remains the preferred everyday drink.

Citrus-containing fluids may also be useful because citrate is a natural inhibitor of calcium stone formation, although the citrate content and sugar load of different beverages vary considerably.

The practical message is therefore not that a patient can never have another soft drink. Rather:

make water the routine drink and soft drinks the occasional one.

The kidneys are generally more interested in what happens every day than what happens at the occasional barbecue.

Preventative medication

Medication is not required for every patient.

Treatment should ideally be directed by stone analysis, metabolic assessment and 24-hour urine results.

Potassium citrate

Potassium citrate increases urinary citrate.

Citrate is helpful because it binds calcium and inhibits calcium crystal formation.

It can be particularly useful in patients with hypocitraturia.

Potential side effects include:

  • Gastrointestinal discomfort
  • Nausea
  • Diarrhoea
  • Elevated blood potassium in susceptible patients

It requires particular caution in patients with impaired renal function or medications that increase serum potassium.

Current Australian CARI guidance considers potassium citrate an important pharmacological option for prevention of recurrent stones when appropriately indicated.

Thiazide and thiazide-like diuretics

These medications reduce urinary calcium excretion and may be considered in patients with persistent hypercalciuria despite appropriate dietary measures.

Potential side effects include:

  • Low blood pressure
  • Dizziness
  • Low sodium
  • Low potassium
  • Increased uric acid
  • Changes in glucose metabolism

The evidence surrounding thiazides has become more nuanced following recent clinical trials, and treatment should therefore be individualised rather than automatically prescribed to every recurrent calcium stone former.

Allopurinol

Allopurinol is not a routine treatment for every calcium oxalate stone former.

It may have a role in selected patients with hyperuricosuria or other specific metabolic abnormalities.

Treatment should be guided by appropriate biochemical evaluation rather than simply by the presence of a calcium oxalate stone.

The pros and cons of the main approaches

Treatment Advantages Disadvantages
Observation No surgery or anaesthetic Stone may grow, move or cause future symptoms
Medical expulsive therapy May help selected ureteric stones pass Not suitable for infection, significant obstruction or large stones
Shock-wave lithotripsy Non-invasive, relatively quick recovery May require repeat treatment; fragments must pass; harder stones may resist fragmentation
Ureteroscopy + laser High clearance rate, direct visual treatment, no skin incision Anaesthetic, possible stent, infection and ureteric injury risks
PCNL Excellent treatment for large renal stone burdens More invasive with greater bleeding and recovery considerations
Preventative medication Can significantly alter relevant urinary risk factors Requires correct patient selection, monitoring and long-term adherence

How effective is treatment?

There is no single “best” treatment for every calcium oxalate stone.

A 5 mm distal ureteric stone, a 12 mm lower-pole renal stone and a 30 mm renal pelvic stone may all be made from exactly the same material, yet require completely different management.

The objective is therefore not simply to treat calcium oxalate, but to treat:

the right stone, in the right patient, with the least invasive treatment likely to achieve reliable clearance.

For appropriately selected ureteric and renal stones, modern flexible ureteroscopy and laser lithotripsy provide excellent clearance with rapid recovery. Larger stone burdens may be better managed with PCNL, while smaller asymptomatic stones may need nothing more than surveillance.

Reducing the risk of another stone

For most calcium oxalate stone formers, prevention revolves around a few principles:

  1. Maintain a high urine volume.
  2. Keep normal dietary calcium rather than unnecessarily restricting it.
  3. Reduce excessive dietary sodium.
  4. Avoid excessive animal protein and high-dose vitamin C supplementation.
  5. Investigate recurrent stone formers metabolically.
  6. Use potassium citrate, thiazide therapy or other preventative medication when a specific metabolic indication exists.
  7. Continue appropriate imaging surveillance.

Australian CARI guidelines emphasise nutrition therapy before pharmacological treatment for many stone formers, with earlier medication appropriate for selected high-risk metabolic abnormalities or patients with a high symptom burden.

The bottom line

Calcium oxalate stones are extremely common, but their treatment has become increasingly precise.

Small uncomplicated stones can often be observed or allowed to pass naturally. Stones requiring treatment can be managed with shock-wave lithotripsy, ureteroscopy with laser fragmentation, or PCNL, depending primarily on their size and location.

Ureteroscopic laser treatment offers excellent access to the urinary tract without an external incision, and modern holmium and thulium fibre lasers can fragment even very hard calcium oxalate calculi. Pre-stenting is useful in selected patients but is not routinely necessary.

Perhaps the most important message comes after the operation: removing the stone is only half the job.

Stone analysis, appropriate imaging and metabolic evaluation can identify why stones are forming. Increased fluid intake, sensible dietary modification and targeted preventative medication can then reduce the likelihood that another small crystal grows into the next large problem.

This information is intended for general patient education and does not replace individual assessment by a urologist. Management should be tailored to stone size and location, kidney function, infection risk, medical history and individual metabolic findings.

So, if you are in trouble with ureteric colic, attend your local Emergency Department for acute management and assessment for urgent stent placement. Further management will be discussed with you thereafter. Ask your GP for a referral to see a Urologist.

Further reading

Dissolution Therapy for Uric Acid Kidney Stones: Can You Really Dissolve a Stone?

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Most kidney stones need to be passed, fragmented or surgically removed. Uric acid stones are different.

Unlike calcium-based stones, a true uric acid stone can often be chemically dissolved inside the urinary tract simply by changing the acidity of the urine. This treatment is known as oral dissolution therapy, urinary alkalinisation or oral chemolysis.

For appropriately selected patients, it can mean avoiding ureteroscopy, laser treatment, shock-wave lithotripsy or percutaneous surgery altogether.

What is a uric acid stone?

Uric acid stones account for approximately 10% of urinary stones, although their frequency varies considerably between populations. They tend to develop when the urine remains persistently acidic, particularly at a urinary pH below approximately 5.5.

Risk factors include:

  • persistently acidic urine
  • low fluid intake and concentrated urine
  • high intake of animal protein and purine-rich foods
  • gout or elevated uric acid
  • obesity and metabolic syndrome
  • diabetes and insulin resistance
  • chronic diarrhoea or intestinal disease
  • high urinary uric acid excretion
  • some haematological disorders and chemotherapy

Importantly, many people who form uric acid stones do not have dramatically elevated blood or urinary uric acid. The major problem is often simply that their urine is too acidic. This is why alkalinising the urine is usually more important than immediately prescribing allopurinol.

Why can uric acid stones be dissolved?

Uric acid is poorly soluble in acidic urine. As urinary pH rises, uric acid becomes increasingly ionised and substantially more soluble.

Think of the stone as a sugar cube sitting in the wrong cup of tea. Change the chemistry of the surrounding fluid and the solid material can gradually return into solution.

The aim of dissolution therapy is therefore to raise the urinary pH sufficiently and keep it elevated throughout the day, allowing the surface of the stone to gradually dissolve.

Current European Association of Urology guidance recommends oral chemolysis using alkaline citrate or sodium bicarbonate, with urine pH generally adjusted to approximately 7.0–7.2 during active dissolution therapy.

How is dissolution therapy performed?

The most commonly used medication is potassium citrate.

Alternative alkalinising agents include:

  • sodium bicarbonate
  • sodium citrate
  • other citrate preparations

Potassium citrate is generally preferred when appropriate because sodium-containing preparations increase sodium intake and may increase urinary calcium excretion. Sodium-based treatment can nevertheless be useful when potassium therapy is unsuitable, particularly when there is concern regarding hyperkalaemia.

The exact dose needs to be individualised according to kidney function, serum electrolytes and, most importantly, the patient’s urinary pH response.

Monitoring your urine pH

This is a crucial part of treatment.

Patients are usually asked to measure their urinary pH at home using suitable pH strips or a pH meter, often at several points during the day.

The dose of alkalinising medication can then be adjusted to keep the urine within the desired range. The EAU specifically recommends teaching patients to monitor their urine pH and modify alkalinising medication accordingly.

The objective is not simply to swallow tablets. It is to achieve and maintain the correct urinary pH.

How effective is dissolution therapy?

When the stone really is composed predominantly of uric acid and urinary alkalinisation is successfully achieved, dissolution therapy can be remarkably effective.

A systematic review involving 1,075 patients reported:

Outcome Approximate rate
Complete dissolution 61.7%
Partial dissolution 19.8%
Complete or partial response 80.5%
Treatment discontinued 10.2%
Required surgical intervention 15.7%

These figures are encouraging, but they also make an important point: dissolution therapy does not work for everyone.

Success depends heavily on correct stone identification, adequate urinary alkalinisation, patient compliance and the size and burden of the stones.

How quickly will the stone disappear?

This varies considerably.

Small stones may respond relatively quickly, while larger stones can require treatment over several months. Dissolution is generally a gradual process rather than an overnight disappearing act.

One clinical series assessing stone volume found that response was associated with achieving a higher urinary pH during treatment, reinforcing the importance of adequate alkalinisation.

Follow-up imaging is therefore important to determine whether the stone is shrinking rather than simply assuming that treatment is working.

How do we know that the stone is uric acid?

This is one of the most important questions.

There is little benefit in trying to dissolve a calcium oxalate stone with urinary alkalinisation. It will remain stubbornly unimpressed.

Evidence suggesting a uric acid stone includes:

  • previous analysis confirming a uric acid stone
  • persistently acidic urinary pH
  • radiolucency on plain X-ray
  • relatively low density on non-contrast CT
  • appropriate clinical and metabolic risk factors

Dual-energy CT can sometimes help differentiate uric acid from non-uric-acid stones.

Stone composition should therefore be assessed as accurately as possible before embarking on prolonged dissolution therapy.

Advantages of dissolution therapy

The biggest advantage is obvious: it is non-invasive.

Successful treatment may avoid anaesthesia and procedures such as ureteroscopy, laser lithotripsy, shock-wave lithotripsy or PCNL.

Other potential advantages include:

  • no surgical incision
  • no instrumentation of the urinary tract
  • usually no hospital admission
  • avoidance of anaesthetic risk
  • potentially useful for patients with significant medical comorbidities
  • treatment can simultaneously address the metabolic environment responsible for future uric acid stones
  • relatively inexpensive compared with surgery
  • can potentially treat multiple uric acid stones simultaneously

For the right patient, dissolution therapy can turn a surgical problem into a metabolic one.

What are the disadvantages?

The trade-off is that dissolution therapy requires time, patience and active participation.

Patients need to take medication consistently, maintain good fluid intake, monitor urinary pH and attend follow-up investigations.

Other disadvantages include:

  • dissolution can take weeks or months
  • treatment may fail
  • the stone may only partially dissolve
  • repeated imaging may be required
  • incorrectly identified non-uric-acid stones will not dissolve
  • excessively alkaline urine can encourage formation of calcium phosphate stones
  • patients with obstruction or infection may require urgent intervention rather than simply waiting for dissolution

In the systematic review discussed above, approximately 15.7% of patients ultimately required an intervention despite attempting dissolution therapy.

Side effects of potassium citrate

Potassium citrate is generally well tolerated, but side effects can occur.

The most common are gastrointestinal and may include:

  • nausea
  • abdominal discomfort
  • bloating
  • diarrhoea
  • vomiting

Taking the medication with food may improve gastrointestinal tolerance.

A more important potential complication is hyperkalaemia, meaning an excessively high potassium concentration in the blood.

This is particularly relevant in patients with:

  • impaired kidney function
  • medications that increase potassium
  • significant cardiac disease
  • other conditions affecting potassium regulation

For this reason, kidney function and electrolytes may need monitoring during therapy.

What about sodium bicarbonate?

Sodium bicarbonate can also effectively alkalinise the urine and is an alternative when potassium citrate is unsuitable.

However, the additional sodium load can be undesirable in patients with conditions such as hypertension, fluid retention or heart failure. Sodium-containing alkali may also increase urinary calcium excretion, which is one reason potassium citrate is generally preferred when clinically appropriate.

Can the urine become too alkaline?

Yes.

More alkaline is not endlessly better.

Although increasing urinary pH improves uric acid solubility, excessive alkalinisation can increase the risk of calcium phosphate stone formation. The EAU therefore recommends targeting rather than indiscriminately increasing urinary pH.

This is why home pH monitoring is so useful.

The aim is controlled chemistry, not turning the bladder into a miniature alkaline swimming pool.

What if the stone is obstructing the kidney?

An obstructed kidney requires more caution.

If a uric acid stone is causing significant obstruction, particularly in the presence of infection, deteriorating renal function or uncontrolled symptoms, simply waiting for the stone to dissolve may be inappropriate.

An infected obstructed urinary system is a urological emergency and requires urgent drainage.

Where an obstructing uric acid stone is otherwise suitable for dissolution, urinary drainage with a ureteric stent or nephrostomy may sometimes be performed first, followed by alkalinisation. The EAU recommends oral chemolysis together with urinary drainage where uric acid stones are obstructing the collecting system.

Does allopurinol dissolve uric acid stones?

Not directly in the same way that alkalinisation does.

Allopurinol reduces the production of uric acid and is particularly useful in patients with hyperuricosuria, gout or continued uric acid stone formation despite appropriate management.

However, most uric acid stone formers have excessively acidic urine as the dominant problem. The AUA therefore recommends potassium citrate as first-line therapy for urinary alkalinisation rather than routinely using allopurinol as first-line treatment for every patient with uric acid stones.

Allopurinol may be added when there is significant hyperuricosuria or recurrent stone formation despite appropriate urinary alkalinisation. The EAU similarly recommends allopurinol for hyperuricosuric urate stone formers.

Preventing the stone from coming back

Dissolving the existing stone is only half the job.

Uric acid stone formers are considered at high risk of recurrence, so the underlying metabolic environment should also be addressed.

Long-term prevention may include maintaining a generous fluid intake, moderating excessive animal protein and purine intake, weight and metabolic health management, continued urinary alkalinisation when indicated, and treatment of hyperuricosuria where appropriate.

A metabolic stone assessment, often including blood tests and 24-hour urine collections, can help identify the factors driving recurrent stone formation.

Dissolution therapy versus surgery

There is no universal winner.

Dissolution therapy is particularly attractive when:

  • the stone is highly likely to be uric acid
  • symptoms are controlled
  • there is no untreated infection
  • renal function is satisfactory
  • immediate stone clearance is unnecessary
  • the patient can reliably monitor urinary pH and attend follow-up

Surgical treatment may be preferable when:

  • the diagnosis of uric acid stone is uncertain
  • the stone is causing significant or persistent obstruction
  • infection is present
  • pain is difficult to control
  • rapid stone clearance is required
  • the stone fails to shrink despite adequate alkalinisation
  • the patient prefers definitive treatment

The bottom line

Uric acid stones have one rather convenient weakness: their chemistry can be used against them.

By raising urinary pH with medications such as potassium citrate, genuine uric acid calculi can often be progressively dissolved without an operation. Published evidence suggests that approximately 80% of appropriately treated patients achieve at least partial dissolution, although complete dissolution occurs in a smaller proportion and some patients will ultimately require surgery.

Successful treatment depends on three things: correctly identifying the stone, achieving the appropriate urinary pH, and monitoring the response.

For selected patients, dissolution therapy offers something unusual in stone surgery: rather than breaking the stone, extracting it or blasting it with a laser, we may simply persuade it to disappear.

This information is intended for general patient education and does not replace individual assessment by a urologist. Treatment and urinary pH targets should be individualised, particularly in patients with renal impairment, infection, obstruction or electrolyte abnormalities.