Advanced bladder (urothelial) cancer is treated mainly with systemic therapy. In current 2026 European guidance, enfortumab vedotin plus pembrolizumab is a new first-line standard for patients fit for combination therapy. Platinum-based chemotherapy remains important when that combination is unsuitable or unavailable, and patients without progression after first-line platinum chemotherapy may receive maintenance avelumab. Later treatment can include immunotherapy, antibody-drug conjugates and molecularly targeted therapy according to previous treatment, kidney function, neuropathy, diabetes, performance status and tumour biomarkers.

Platinum chemotherapy

Cisplatin-containing combinations such as gemcitabine-cisplatin are highly active when kidney function and general fitness allow. Carboplatin-based treatment may be used when cisplatin is unsuitable, but the two are not equivalent in all respects. Neoadjuvant cisplatin-based chemotherapy is also standard before cystectomy for eligible non-metastatic MIBC.

Immunotherapy

Checkpoint inhibitors release immune brakes such as PD-1/PD-L1. They are used in multiple advanced-disease settings, including maintenance or later-line therapy and selected patients unsuitable for platinum depending on current regulatory guidance and biomarkers. Immune-related side effects can involve skin, bowel, lungs, liver, endocrine glands, kidneys and other organs.

Enfortumab vedotin and newer systemic treatments

Enfortumab vedotin is an antibody-drug conjugate directed at Nectin-4 and, combined with pembrolizumab, has become a first-line standard for many patients with advanced urothelial cancer. Important toxicities include skin reactions, peripheral neuropathy and hyperglycaemia. FGFR inhibitors such as erdafitinib can be effective in cancers with susceptible FGFR alterations, and later-line sequencing depends strongly on what was already used.

How treatment response is monitored

CT imaging, symptoms, blood counts, kidney/liver function and treatment-specific tests are reviewed. Treatment is changed for progression, unacceptable toxicity or according to planned maintenance/sequence. Response in one scan should be interpreted alongside clinical course.

Supportive care is part of cancer treatment

Pain, urinary obstruction, bleeding, nutrition, kidney drainage, infection, bone health and emotional support should be managed in parallel with anti-cancer therapy. Palliative radiotherapy or urinary diversion/stenting may relieve symptoms even when systemic therapy is the main treatment.

The first-line landscape has changed rapidly

For many patients with locally advanced or metastatic urothelial cancer who are suitable for combination therapy, enfortumab vedotin plus pembrolizumab has become a major first-line standard. Platinum chemotherapy remains important when this regimen is unsuitable or unavailable, and the exact sequence is influenced by renal function, neuropathy, diabetes, performance status and previous peri-operative therapy.

Peri-operative treatment for muscle-invasive disease is also evolving

For cisplatin-eligible MIBC, cisplatin/gemcitabine with peri-operative durvalumab is now incorporated into 2026 EAU recommendations alongside established cisplatin-based neoadjuvant chemotherapy pathways. For selected cisplatin-ineligible patients, peri-operative enfortumab vedotin plus pembrolizumab has also entered guideline pathways. Availability and regulatory approval vary by country, so local access must be checked rather than assumed.

Molecular testing becomes relevant in later lines

FGFR3 alterations can identify patients who may benefit from erdafitinib in appropriate advanced-disease settings. HER2 expression can also influence later-line options in current guidance. Biomarker testing should therefore be planned early enough that results are available when sequencing decisions arise.

When to seek earlier medical review

During systemic treatment, urgent assessment is needed for fever, severe skin reactions, uncontrolled hyperglycaemia symptoms, marked breathlessness, confusion or severe diarrhoea. Neuropathy should be reported early because cumulative nerve damage can influence enfortumab dosing.

What to bring to your consultation

• Pathology and staging scans
• Previous systemic-treatment timeline
• Recent blood counts/kidney/liver tests
• Neuropathy, diabetes and medication history

Questions to ask your doctor

• Am I eligible for enfortumab vedotin plus pembrolizumab as first-line therapy?
• If this is peri-operative MIBC treatment, which 2026 pathway applies to my cisplatin fitness?
• Has my tumour been tested for actionable FGFR or relevant HER2 expression?

FAQs

Related reading

• Bladder Cancer: Symptoms and Treatment
• TURBT Explained
• Bladder Cancer Stages Explained: Ta, T1, T2 and Beyond
• Carcinoma in Situ (CIS) of the Bladder Explained
• BCG-Unresponsive Bladder Cancer: What Happens Next?
• Intravesical Chemotherapy for Bladder Cancer
• Immunotherapy for Kidney Cancer
• Chemotherapy for Advanced Prostate Cancer
• Urologist in Latur

References

• European Association of Urology (EAU). Non-muscle-invasive Bladder Cancer Guidelines https://uroweb.org/guidelines/non-muscle-invasive-bladder-cancer
• European Association of Urology (EAU). Muscle-invasive and Metastatic Bladder Cancer Guidelines. Disease Management https://uroweb.org/guidelines/muscle-invasive-and-metastatic-bladder-cancer/chapter/disease-management
• National Cancer Institute. Bladder Cancer Treatment (PDQ) – Patient Version https://www.cancer.gov/types/bladder/patient/bladder-treatment-pdq
• EAU Muscle-invasive and Metastatic Bladder Cancer Guidelines 2026. Metastatic Disease https://uroweb.org/guidelines/muscle-invasive-and-metastatic-bladder-cancer/chapter/metastatic-disease