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Urinary bladder (urinary tract)

Bladder cancer

How occupational and tobacco links, BCG, cisplatin chemotherapy, immunotherapy and antibody-drug conjugates shaped bladder cancer care.

5-year relative survival · United States, SEER 8 registries

72.22%→82.24%

1975 (observed value; first year in the table and the lowest observed value) to 2018 (observed value; last observed year in the table and the highest observed value). Read these with the caveats under “Then and now”.Source

26 milestones, by decade

  • A 2012 historical review states that in 1895 the Frankfurt surgeon Ludwig Rehn described three cases of occupational bladder tumour among at most 45 fuchsine workers, that many more cases among workers in the paint industry were described afterwards, and that beta-naphthylamine, an aromatic amine, was banned from the 1950s in Germany and many other countries. A history-of-medicine bibliography lists Rehn's paper (Archiv für klinische Chirurgie 50:588-600, 1895). Rehn's own paper was not read, so every statement is attributed to the review or the listing, and no single causative chemical is assigned here; 'aromatic amines in the dye industry' is the closest supported wording.
  • On the SEER Cancer Stat Facts page for bladder cancer, the US age-adjusted death rate is 5.50 per 100,000 in 1975 and 3.92 in 2024, while observed 5-year relative survival in the SEER 8 series is 72.22% for 1975 and 82.24% for 2018. The page puts half of all cases at in situ stage; in SEER 21 data for 2016-2022, 5-year relative survival is 98.0% for in situ stage and 9.6% for distant stage. These are different series (US mortality data and a limited set of registries), the page assigns the change to no cause, and, as a general point the page does not make, survival measured from diagnosis can be affected by earlier detection. For a cancer in which half of cases are found in situ, an all-stage survival figure and the survival of people with distant disease answer different questions.
  • Four FDA accelerated approvals in urothelial cancer were later removed from the label. The agency's letters are dated 19 February 2021 (durvalumab), 13 April 2021 (atezolizumab after platinum chemotherapy), 2 December 2022 (atezolizumab for people not eligible for cisplatin) and 22 November 2024 (sacituzumab govitecan, withdrawn voluntarily). The first three letters give no reason; the sacituzumab letter states that the required confirmatory trial was fulfilled but did not confirm clinical benefit. These are US actions: the EMA page for atezolizumab read on 20 October 2026 still lists a urothelial monotherapy indication.

Evidence current to October 2026 · Checked against primary sources to the extent possible

A guided tour of 12 milestones. You can pause or step through it yourself.

Filter milestonesshowing all 26
Treatment type
Setting

The age of rays

  1. 1895 · Understanding · UnderstandingBladder tumours among fuchsine workers: Rehn, 1895In 1895 the surgeon Ludwig Rehn described three cases of bladder tumour among at most 45 fuchsine workers in Frankfurt, according to a 2012 historical review. Later reports covered many more cases in the paint industry, and from the 1950s beta-naphthylamine, an aromatic amine, was banned in Germany and many other countries.Historical series, no randomisation. Per a 2012 review, Rehn in 1895 described 3 cases of occupational bladder tumour among at most 45 fuchsine workers in Frankfurt; many more cases among workers in the paint industry were described afterwards. Hueper induced bladder cancer in dogs with beta-naphthylamine in the 1930s. A two-part British report in 1954 (Case and colleagues) dealt with aniline, benzidine and the naphthylamines (titles only).

Chemotherapy

  1. 1962 · Treatment · SurgeryRadical cystectomy series: Whitmore and Marshall 1962, Stein 2001A 1962 journal report by Whitmore and Marshall carries the title 'Radical total cystectomy for cancer of the bladder: 230 consecutive cases five years later'; only the title is available to this site, so its results are not summarised. A later series of 1,054 patients reported that 68% were free of recurrence at five years.Whitmore and Marshall (J Urol 1962): '230 consecutive cases five years later' of radical total cystectomy (title only; no outcome data recorded). Stein et al. (J Clin Oncol 2001): 1,054 patients, radical cystectomy with bilateral pelvic lymphadenectomy, median follow-up 10.2 years; recurrence-free survival 68% at 5 and 66% at 10 years; 27 perioperative deaths (2.5%); 246 patients (24%) node-positive, 5-year recurrence-free survival 35%.

Molecular origins

  1. 1976 · Treatment · ImmunotherapyIntravesical BCG for recurrent superficial bladder tumoursIn 1976 a series reported giving BCG, a bacterial preparation, into the bladder and under the skin of people whose superficial bladder tumours kept returning. The pattern of recurrence changed favourably in nine patients, and the authors called the findings preliminary.Treated series, no comparison group mentioned in the abstract: patients with recurrent superficial bladder tumours received vesical and intradermal BCG. In 9 patients the pattern of recurrence was altered favourably; the authors called the findings preliminary and said they appeared to hold promise of a new therapeutic approach. The four-sentence abstract does not say how many patients were treated in all and gives no rates, intervals or follow-up.
  2. 1985 · Treatment · ChemotherapyMVAC: combination chemotherapy for advanced urothelial cancerIn 1985 a series of 25 people reported that four drugs given together, methotrexate, vinblastine, doxorubicin and cisplatin, shrank advanced bladder cancer in most of them, and about half of those with measurable disease had a complete clinical remission. A later randomised trial compared the combination with cisplatin alone.1985 single-arm series (N=25): complete clinical remission in 12 of 24 patients with measurable lesions (50%; 95% CI 30-70%); median response duration not reached at 9.5+ months. Randomised intergroup trial (246 assessable): M-VAC vs cisplatin alone, response rate 39% vs 12% (P<0.0001), median PFS 10.0 vs 4.3 months, median OS 12.5 vs 8.2 months.
  3. 1991 · Treatment · ImmunotherapyBCG versus intravesical doxorubicin, then BCG maintenanceIn a 1991 randomised trial of people whose bladder tumours kept returning, BCG, a bacterial preparation placed in the bladder, kept more people free of disease at five years than the chemotherapy drug doxorubicin (about two in five versus about one in six, without carcinoma in situ). A later randomised study found scheduled BCG maintenance lengthened the time before recurrence.Randomised multi-institutional trial of intravesical doxorubicin versus BCG (intravesical and percutaneous), 262 eligible patients, median follow-up 65 months. Ta/T1 without CIS: 5-year disease-free probability 17% versus 37% (P=0.015). CIS: complete response 34% versus 70% (P<0.001). SWOG maintenance trial (384 analysed): median RFS 35.7 versus 76.8 months with maintenance (P<0.0001).

Targeted therapy

  1. 1999 · Treatment · Chemotherapy⚑ needs reviewNeoadjuvant cisplatin-based chemotherapy before cystectomyRandomised trials asked whether platinum-based chemotherapy before bladder surgery helps people with muscle-invasive bladder cancer live longer. Two large trials did not reach statistical significance at first report; in one, median survival was 77 months with chemotherapy and 46 without. A pooled analysis of ten trials found five-year survival rose from 45% to 50% with platinum-based combinations.US randomised trial (317 enrolled; 154 cystectomy alone vs 153 MVAC then cystectomy): median OS 46 vs 77 months, P=0.06 (ITT); no residual disease at cystectomy 15% vs 38%. MRC/EORTC BA06 30894 (976 patients, no chemotherapy vs CMV): 3-year survival 50.0% vs 55.5% (P=0.075); long-term OS HR 0.84 (95% CI 0.72-0.99), 10-year 30% vs 36%. Meta-analysis (2688 patients, ten trials): platinum-combination OS HR 0.87 (0.78-0.98); 5-year 45% vs 50%.
  2. 2000 · Treatment · ChemotherapyGemcitabine-cisplatin compared with MVAC in advanced bladder cancerIn 405 people with advanced bladder (urothelial) cancer who had not had chemotherapy, gemcitabine plus cisplatin and the older four-drug MVAC regimen gave similar survival. The two-drug regimen caused fewer of several serious side effects, such as fever with low white blood cells.Randomised phase 3 (N=405; gemcitabine-cisplatin n=203, MVAC n=202). Overall survival HR 1.04 (95% CI 0.82-1.32; P=.75); response rate 49% vs 46%; toxic death 1% vs 3%. Long-term update: median OS 14.0 vs 15.2 months (HR 1.09; 95% CI 0.88-1.34), 5-year OS 13.0% vs 15.3%. Neutropenic sepsis 1% vs 12%.
  3. 2006 · Understanding · UnderstandingEORTC risk tables for non-muscle-invasive bladder cancerIn 2006 researchers pooled data from about 2,600 people in seven European trials to build tables that estimate an individual's chance of bladder tumour recurrence and progression after surgery, using six clinical and pathological factors. The estimated five-year chance of recurrence ranged from about three in ten to about four in five.Combined analysis of individual data from 2596 patients with stage Ta T1 bladder cancer in seven EORTC trials. A score uses six factors: number of tumours, size, prior recurrence rate, T category, carcinoma in situ and grade. Probability of recurrence ranged from 15% to 61% at one year and 31% to 78% at five years; progression from under 1% to 17% at one year and under 1% to 45% at five years.

Immunotherapy

  1. 2011 · Understanding · UnderstandingSmoking and bladder cancer risk in a large US cohortIn a large US cohort followed from 1995 to 2006, current smokers had about four times, and former smokers about twice, the bladder cancer risk of people who never smoked. The authors found higher relative risks than in earlier US cohorts and estimated that about half of cases in both sexes were attributable to smoking.NIH-AARP cohort, follow-up 1995-2006 (about 4.5 million person-years): bladder cancer in 3896 men and 627 women. Versus never smokers (39.8 per 100000 person-years), hazard ratio 2.22 (95% CI 2.03 to 2.44) for former and 4.06 (3.66 to 4.50) for current smokers. Summary relative risk for current smoking in 7 earlier cohorts (begun 1963-1987) 2.94 (2.45 to 3.54). Population attributable risk for ever smoking 0.50 in men, 0.52 in women.
  2. c. 2012 · Understanding · ImmunotherapyBCG shortages from about 2012 limit intravesical therapyBCG, a critical treatment for higher-risk non-muscle-invasive bladder cancer, ran short twice within about three years, the second time announced in 2014, according to a urologist's 2017 commentary. In a French single-centre study, people affected by the 2012 to 2014 shortage more often could not complete BCG induction and maintenance.Commentary (Messing 2017) plus a retrospective single-centre French study of high-risk NMIBC. In the study, BCG induction could not be completed in 20.8% of patients impacted by the 2012-2014 Connaught-strain shortage versus 5.3% of those not impacted (P=0.02); maintenance was incomplete in 56.6% versus 37.5% (P=0.047). No significant difference in recurrence-free, progression-free, overall or specific survival; cystectomy rate higher in the impacted group.
  3. 2012 · Treatment · RadiationBC2001: chemotherapy added to radiotherapy for bladder preservationRadiotherapy is an alternative to bladder removal for some people with muscle-invasive bladder cancer. In the BC2001 trial, adding two chemotherapy drugs to radiotherapy improved control of the cancer in the bladder area: at two years 67% were alive and free of locoregional (bladder and pelvic) disease versus 54%. Differences in survival were not statistically significant.BC2001 (phase 3, 2 x 2 factorial; 360 randomised to radiotherapy 178 vs radiotherapy plus fluorouracil and mitomycin C 182). 2-year locoregional DFS 67% vs 54% (HR 0.68, 95% CI 0.48-0.96); 5-year OS 48% vs 35% (HR 0.82, 0.63-1.09, P=0.16). At 9.9 years' median follow-up (ITT): locoregional control HR 0.61 (0.43-0.86); OS HR 0.88 (0.69-1.13); 5-year cystectomy rate 14% vs 22%.
  4. 2017 · Treatment · ImmunotherapyKEYNOTE-045: pembrolizumab after platinum in advanced UCIn 542 people whose advanced bladder cancer had progressed after platinum chemotherapy, pembrolizumab was linked to median survival of about 10 months compared with about 7 months for chemotherapy. Serious treatment-related side effects were less frequent with pembrolizumab.Open-label phase 3 (N=542; pembrolizumab n=270, chemotherapy n=272): median OS 10.3 vs 7.4 months (HR 0.73; 95% CI 0.59-0.91; P=0.002); PD-L1 CPS of 10% or more, 8.0 vs 5.2 months (HR 0.57). PFS HR 0.98 (95% CI 0.81-1.19). Grade 3-5 treatment-related events 15.0% vs 49.4%. Update: 2-year OS 26.9% vs 14.3%.
  5. 2019 · Treatment · Antibody–drug conjugateEnfortumab vedotin after platinum and PD-1/PD-L1: EV-201, EV-301Enfortumab vedotin is an antibody-drug conjugate aimed at a protein called Nectin-4. In a phase 2 study, tumours shrank in about four in ten people whose bladder cancer had progressed after platinum and immunotherapy. In a randomised trial of 608 people, median survival was about 13 months versus about 9 with chemotherapy.EV-201 (phase 2, single-arm, cohort 1, n=125): confirmed ORR 44% (95% CI 35.1-53.2), 12% complete responses; median DOR 7.6 months. EV-301 (phase 3, N=608): median OS 12.88 vs 8.97 months (HR 0.70; 95% CI 0.56-0.89; P=0.001); median PFS 5.55 vs 3.71 months (HR 0.62). EV-201 cohort 2 (n=89, cisplatin-ineligible): ORR 52%.
  6. 2019 · Treatment · TargetedErdafitinib for FGFR-altered urothelial cancer: BLC2001 to THORErdafitinib is a tablet that blocks FGFR proteins. In a phase 2 study, 40 in every 100 people with FGFR-altered advanced bladder cancer had a response. In a later randomised trial after immunotherapy, median survival was about 12 months with erdafitinib versus about 8 with chemotherapy.BLC2001 (phase 2, n=99 selected regimen): confirmed ORR 40%; median PFS 5.5 and OS 13.8 months. THOR cohort 1 (phase 3, N=266, after anti-PD-1/PD-L1): median OS 12.1 vs 7.8 months (HR 0.64; 95% CI 0.47-0.88; P=0.005); PFS 5.6 vs 2.7 months. THOR cohort 2 (N=351, vs pembrolizumab): OS 10.9 vs 11.1 months (HR 1.18; 95% CI 0.92-1.51).

Precision & engineered

  1. 2020 · Treatment · ImmunotherapyJAVELIN Bladder 100: avelumab maintenance after chemotherapyIn 700 people whose advanced bladder cancer had not progressed after first-line platinum chemotherapy, adding avelumab maintenance to supportive care was linked to median survival of about 21 months compared with about 14 months with supportive care alone.Phase 3 (N=700): maintenance avelumab plus best supportive care vs best supportive care alone after four to six cycles of gemcitabine with cisplatin or carboplatin. Median OS 21.4 vs 14.3 months (HR 0.69; 95% CI 0.56-0.86; P=0.001); 1-year OS 71.3% vs 58.4%. PD-L1-positive tumours: HR 0.56 (95% CI 0.40-0.79). Grade 3 or higher adverse events 47.4% vs 25.2%.
  2. 2020 · Treatment · Immunotherapy⚑ needs reviewKEYNOTE-057: pembrolizumab for BCG-unresponsive CISIn a single-group study of people whose carcinoma in situ no longer responded to BCG and who could not or chose not to have the bladder removed, pembrolizumab, an immune checkpoint inhibitor, led to a complete response at three months in about two in five. US regulators approved it for this group in January 2020.Phase 2 single-arm cohort A (101 enrolled): pembrolizumab 200 mg every 3 weeks for up to 24 months in BCG-unresponsive CIS, ineligible for or declining cystectomy. Complete response at 3 months 41% (39/96; 95% CI 30.7 to 51.1) in the efficacy population; median follow-up 36.4 months. Grade 3 or 4 treatment-related adverse events 13%. FDA supplement approval 8 January 2020.
  3. 2020 · Treatment · ImmunotherapyNadofaragene firadenovec for BCG-unresponsive NMIBCNadofaragene firadenovec is a gene therapy placed in the bladder that delivers instructions for making interferon alfa-2b. In a single-group study of people whose cancer no longer responded to BCG, just over half of those with carcinoma in situ had a complete response; fewer than half of these held at one year. The US approved it in December 2022.Phase 3 single-arm study (157 enrolled, 33 US centres): intravesical nadofaragene firadenovec, repeated at months 3, 6 and 9 if no high-grade recurrence. Per-protocol CIS cohort: complete response within 3 months 53.4% (55/103); maintained at 12 months in 25 of 55 (45.5%); null hypothesis CR below 27%. FDA BLA approval 16 December 2022 (CBER).
  4. 2021 · Reversal · ImmunotherapyAtezolizumab and durvalumab urothelial indications withdrawnBetween 2021 and 2022 the US FDA removed three accelerated approvals for PD-L1 inhibitors in bladder cancer: durvalumab and atezolizumab after platinum chemotherapy, and atezolizumab for people who could not have cisplatin. They had been granted on response-rate data. In the randomised IMvigor211 trial, survival did not differ significantly in the first group tested, people with higher PD-L1.FDA accelerated approvals: durvalumab 1 May 2017 (removal letter 19 Feb 2021); atezolizumab post-platinum 18 May 2016 (removal 13 Apr 2021); atezolizumab cisplatin-ineligible 17 Apr 2017 (removal 2 Dec 2022). IMvigor211 (N=931): OS in the PD-L1 IC2/3 group 11.1 vs 10.6 months (HR 0.87; 95% CI 0.63-1.21; P=0.41). IMvigor210 cohort 2: ORR 15% overall.
  5. 2021 · Treatment · Immunotherapy⚑ needs reviewCheckMate 274: adjuvant nivolumab after radical surgeryAfter surgery for high-risk muscle-invasive urothelial cancer, up to a year of nivolumab was compared with placebo. Median time free of disease was about 21 months with nivolumab and 11 months with placebo. Severe (grade 3 or higher) treatment-related side effects were more frequent with nivolumab. The FDA approved adjuvant nivolumab in August 2021.CheckMate 274 (phase 3, double-blind, n=709): adjuvant nivolumab 240 mg every 2 weeks for up to 1 year vs placebo after radical surgery. ITT median DFS 20.8 vs 10.8 months; 6-month DFS 74.9% vs 60.3%; HR 0.70 (98.22% CI 0.55-0.90, P<0.001). PD-L1 1% or more: 6-month 74.5% vs 55.7%, HR 0.55 (98.72% CI 0.35-0.85). Grade 3 or higher treatment-related adverse events 17.9% vs 7.2%. FDA approval 19 August 2021.
  6. 2022 · Treatment · ImmunotherapyN-803 plus BCG in BCG-unresponsive NMIBCNogapendekin alfa inbakicept (N-803) is an interleukin-15 activator given into the bladder together with BCG. In a single-group study of people whose carcinoma in situ no longer responded to BCG, about seven in ten had a complete response. The US regulator approved it in April 2024.QUILT-3.032 cohort A (82 patients, BCG-unresponsive CIS with or without papillary disease): NAI plus BCG, complete response 71% (58/82; 95% CI 59.6 to 80.3), median duration 26.6 months; at 24 months in responders, cystectomy avoidance 89.2%, bladder cancer-specific survival 100%. Cohort B (72 papillary): 12-month DFS 55.4% (95% CI 42.0 to 66.8). FDA approval 22 April 2024.
  7. 2023 · Treatment · Antibody–drug conjugateEV-302: enfortumab vedotin plus pembrolizumab as first-lineIn 886 people with untreated advanced bladder (urothelial) cancer, enfortumab vedotin plus pembrolizumab was linked to median survival of about 31.5 months, compared with about 16 months for platinum-based chemotherapy. Side effects differed between the two treatments.Open-label phase 3 (N=886): enfortumab vedotin plus pembrolizumab vs gemcitabine plus cisplatin or carboplatin. Median PFS (blinded central review) 12.5 vs 6.3 months (HR 0.45; 95% CI 0.38-0.54); median OS 31.5 vs 16.1 months (HR 0.47; 95% CI 0.38-0.58); both P<0.001. At 2.5 years' median follow-up, OS HR 0.51 (95% CI 0.43-0.61). FDA regular approval 15 December 2023.
  8. 2024 · Treatment · ImmunotherapyNIAGARA: durvalumab added to neoadjuvant gemcitabine-cisplatinIn people with muscle-invasive bladder cancer who could receive cisplatin, adding the immunotherapy durvalumab before and after surgery to standard chemotherapy was tested against chemotherapy alone. At two years, 68% were event-free versus 60%, and 82% were alive versus 75%. The FDA approved the regimen in March 2025.NIAGARA (phase 3, n=1063, cisplatin-eligible MIBC): neoadjuvant durvalumab plus gemcitabine-cisplatin, cystectomy, adjuvant durvalumab vs gemcitabine-cisplatin then cystectomy alone. 24-month EFS 67.8% vs 59.8% (HR 0.68, 95% CI 0.56-0.82, P<0.001); 24-month OS 82.2% vs 75.2% (HR 0.75, 0.59-0.93, P=0.01). Cystectomy performed in 88.0% vs 83.2%; grade 3 or 4 treatment-related adverse events 40.6% vs 40.9%. FDA approval 28 March 2025.
  9. 2024 · Reversal · Antibody–drug conjugateSacituzumab govitecan urothelial indication withdrawnIn 2021 the FDA granted accelerated approval to sacituzumab govitecan for advanced bladder cancer after platinum chemotherapy and immunotherapy, based on a single-arm study in which about 27 in 100 people responded. In 2024 the indication was withdrawn at the sponsor's request; the FDA letter says the confirmatory randomised trial did not confirm clinical benefit.TROPHY-U-01 cohort 1 (phase 2, single-arm, n=113): ORR 27% (95% CI 19.5-36.6), median DOR 7.2 months, median OS 10.9 months. TROPiCS-04 (phase 3, N=711): median OS 10.3 vs 9.0 months (HR 0.86; 95% CI 0.73-1.02; P=0.087); primary endpoint not met. FDA accelerated approval 13 April 2021; voluntary withdrawal 22 November 2024.
  10. 2025 · Treatment · Antibody–drug conjugateKEYNOTE-905/EV-303: EV plus pembrolizumab around cystectomyFor people with muscle-invasive bladder cancer who could not or chose not to have cisplatin chemotherapy, enfortumab vedotin plus pembrolizumab before and after surgery was compared with surgery alone. At two years, 75% were event-free versus 39%, and 80% were alive versus 63%. The FDA approved the combination for this group in November 2025.KEYNOTE-905/EV-303 (phase 3; 344 randomised: 170 EV-pembrolizumab, 174 surgery alone; MIBC ineligible for or declining cisplatin). Median follow-up 25.6 months. 2-year EFS 74.7% vs 39.4% (HR 0.40, 95% CI 0.28-0.57); OS 79.7% vs 63.1% (HR 0.50, 0.33-0.74); pCR 57.1% vs 8.6%. Grade 3 or higher adverse events 71.3% vs 45.9%. FDA approval 21 November 2025 (cisplatin-ineligible).
  11. 2025 · Treatment · ChemotherapyTAR-200 for BCG-unresponsive high-risk NMIBCTAR-200 is an intravesical drug-releasing system that delivers gemcitabine into the bladder. In a phase 2 study of people with carcinoma in situ that no longer responded to BCG, about four in five of those given TAR-200 alone had a complete response. The US regulator approved it, as Inlexzo, in September 2025.SunRISe-1 (phase IIb, parallel cohorts, no statistical comparison between them), BCG-unresponsive high-risk NMIBC. CIS: complete response 82.4% (95% CI 72.6 to 89.8) with TAR-200 alone, median duration 25.8 months; 67.9% with cetrelimab added; 46.4% with cetrelimab alone. Papillary only (TAR-200 alone): 12-month DFS 70.2% (95% CI 51.6 to 82.8). Grade 3 or worse treatment-related adverse events 12.9% (TAR-200 alone, CIS). FDA approval 9 September 2025.
  12. 2026 · Treatment · Antibody–drug conjugateKEYNOTE-B15/EV-304: EV-pembrolizumab versus cisplatin-gemcitabineIn people with muscle-invasive bladder cancer who could receive cisplatin, enfortumab vedotin plus pembrolizumab before and after surgery was compared with cisplatin-gemcitabine chemotherapy before surgery. At two years, 79% were event-free versus 66%, and 87% were alive versus 81%. Severe side effects were more frequent with the new combination. The FDA approved it in July 2026.KEYNOTE-B15/EV-304 (phase 3, n=808, cisplatin-eligible MIBC): perioperative EV-pembrolizumab (405) vs neoadjuvant cisplatin-gemcitabine then cystectomy (403). Median time to data cutoff 33.6 months. 2-year EFS 79.4% vs 66.2% (HR 0.53, 95% CI 0.41-0.70); OS 86.9% vs 81.3% (HR 0.65, 0.48-0.89, P=0.006); pCR 55.8% vs 32.5%. Grade 3 or higher adverse events 75.7% vs 67.2%. FDA approval 10 July 2026.

Then and now

  • 5-year relative survival · United States, SEER 8 registries

    • 72.22%

      1975 (observed value; first year in the table and the lowest observed value)

    Both sexes, all races; bladder cancer, all stages together; the SEER 8 five-year relative survival series (1975-2018) on the SEER Cancer Stat Facts bladder page. The page states no age range or histology for this series.

    Modeled trend value for 1975: 72.84%. Relative survival excludes deaths from other causes. 'Observed' is the table's label for the yearly value, as opposed to the Joinpoint modeled-trend value in the adjacent column. The column is headed 'Year' and the chart note says only 'SEER 8 5-Year Relative Survival Percent from 1975-2018'; the page does not say the year is the year of diagnosis. SEER 8 covers a limited set of registries. The page reports that half of all bladder cancer cases (50%) are in situ stage (SEER Combined Summary Stage: only in the originating layer of cells) and does not describe how stage mix, detection or coding changed over time, so a change in this all-stage series may reflect those factors as well as treatment; the page apportions it to no cause. Read beside the mortality values. Compare only with other values from this same SEER 8 series, not with the SEER 21 values.

    Source

  • 5-year relative survival · United States, SEER 8 registries

    • 82.24%

      2018 (observed value; last observed year in the table and the highest observed value)

    Both sexes, all races; bladder cancer, all stages together; same SEER 8 series (1975-2018). The page states no age range or histology for this series.

    Modeled trend value for 2018: 80.04%; the table shows no observed five-year value for 2019 onward (modeled trend only, 80.03% for 2019). The observed series moves from year to year (for example 78.31% in 2010 and 81.72% in 2015). Relative survival excludes deaths from other causes. 'Observed' is the table's label for the yearly value, as opposed to the Joinpoint modeled-trend value in the adjacent column. The column is headed 'Year' and the chart note says only 'SEER 8 5-Year Relative Survival Percent from 1975-2018'; the page does not say the year is the year of diagnosis. SEER 8 covers a limited set of registries. The page reports that half of all bladder cancer cases (50%) are in situ stage (SEER Combined Summary Stage: only in the originating layer of cells) and does not describe how stage mix, detection or coding changed over time, so a change in this all-stage series may reflect those factors as well as treatment; the page apportions it to no cause. Read beside the mortality values. Compare only with other values from this same SEER 8 series, not with the SEER 21 values.

    Source

  • 5-year relative survival · United States, SEER 21 (excluding IL)

    • 79.1%

      2016-2022

    Both sexes, all races, all ages (the page states no age range for the headline figure); bladder cancer, all stages together.

    A different registry set and period from the SEER 8 series: do not subtract it from the 1975 value. Half of cases (50%) in this data are in situ stage, so the all-stage figure largely reflects disease confined to the originating layer of cells; stage-specific values are listed in the next records. Relative survival excludes deaths from other causes.

    Source

  • 5-year relative survival · United States, SEER 21 (excluding IL)

    • 98%

      2016-2022; in situ stage at diagnosis (50% of cases)

    Both sexes, all races, SEER Combined Summary Stage 'In Situ: only in originating layer of cells'. The page gives no further definition of what is coded in situ for the bladder.

    Stage-specific values come from the same SEER 21 data as the headline figure and are not comparable with the SEER 8 yearly series. Stage at diagnosis is a strong influence on survival, according to the page; separately, and not stated on the page, survival measured from diagnosis can rise with earlier detection without changing the date of death. Relative survival excludes deaths from other causes.

    Source

  • 5-year relative survival · United States, SEER 21 (excluding IL)

    • 73%

      2016-2022; localized stage at diagnosis (34% of cases)

    Both sexes, all races, SEER Combined Summary Stage 'Localized: confined to primary site'. The page text gives the share diagnosed at the local stage as 34.3%.

    Same data and cautions as the in situ record. The page does not separate non-muscle-invasive from muscle-invasive disease within the localized group.

    Source

  • 5-year relative survival · United States, SEER 21 (excluding IL)

    • 41.8%

      2016-2022; regional stage at diagnosis (7% of cases)

    Both sexes, all races, SEER Combined Summary Stage 'Regional: spread to regional lymph nodes'.

    Same data and cautions as the in situ record. Unstaged disease (3% of cases; 5-year relative survival 50.8%) is not entered as a record.

    Source

  • 5-year relative survival · United States, SEER 21 (excluding IL)

    • 9.6%

      2016-2022; distant stage at diagnosis (6% of cases)

    Both sexes, all races, SEER Combined Summary Stage 'Distant: cancer has metastasized'.

    Same data and cautions as the in situ record. This is the stage most relevant to the advanced-disease milestones; the page gives no earlier distant-stage series, and the figure describes people diagnosed in 2016-2022, not the outcome of any one regimen.

    Source

  • Age-standardised mortality · United States

    • 5.5per 100,000

      1975 (observed value; first year in the table)

    Both sexes, all races, all ages; age-adjusted death rate (the 'Death Rate - U.S.' column of the SEER bladder table).

    Deaths come from U.S. mortality data, not from SEER registries, so this is a different series from the survival values. The highest value in the table is 5.59 in 1976. The modeled-trend value for 1975 is 5.53. The page attributes the change in the rate to no cause; mortality reflects incidence, detection and treatment together.

    Source

  • Age-standardised mortality · United States

    • 4.33per 100,000

      2000 (observed value)

    Same series (U.S. mortality, age-adjusted, both sexes, all races).

    Same series and cautions as the 1975 record. The observed values in the table are 4.36 in 1995 and 4.46 in 2015, so the rate stayed between about 4.3 and 4.5 over those two decades before falling.

    Source

  • Age-standardised mortality · United States

    • 3.92per 100,000

      2024 (observed value; last year in the table and the lowest value in it)

    Same series (U.S. mortality, age-adjusted, both sexes, all races).

    The page headline gives 4.1 per 100,000 for 2020-2024 deaths (age-adjusted): use one value or the other, not both. The page reports death rates falling on average 1.3% a year over 2015-2024. Same series and cautions as the 1975 record.

    Source

  • 10-year relative survival · United Kingdom

    • 35.4%

      1970s (as labelled on the page)

    People diagnosed with bladder cancer in the UK; the CRUK page states that more than 1 in 3 (35.4%) survived their disease beyond ten years. Age range and the exact diagnosis period are not stated beside the figure.

    The page does not name the measure (net, relative or observed survival) or the age standardisation, and the metric label is the nearest available; the page states that survival trends reflect a combination of changes in treatment and stage distribution. Not comparable with the US SEER series.

    Source

  • 10-year relative survival · United Kingdom

    • 42.3%

      2018 (as labelled on the page; described as predicted)

    People diagnosed with bladder cancer in the UK; the page states that it is predicted that more than 4 in 10 (42.3%) survive their disease for ten years or more (2018). Ten-year survival is lower in females than in males (2018): for ages 15-44 the page gives 48.3% (females) and 67.1% (males), for ages 75-99 it gives 23.1% (females) and 37.1% (males).

    Described on the page as predicted, so a modelled estimate rather than an observed ten-year follow-up. The page says ten-year survival has increased in some broad age groups and decreased in others since the early 1970s. Five-year survival in England for 2015-2019 is 47.6% on the same page (not entered as a record). Same series and measure caveats as the 1970s value.

    Source

Survival figures are affected by earlier detection (lead time) and overdiagnosis, and by changes in who is diagnosed. For screened cancers, read them alongside mortality.

Evidence chains

A lane follows one defined population and setting, where each new trial tests against what was then standard. Compare only within a lane, and read every comparison as illustrative.

Non-muscle-invasive disease: intravesical BCG versus doxorubicin

Patients with rapidly recurrent stage Ta or T1 transitional-cell carcinoma of the bladder without carcinoma in situ (1991 randomised comparison) · Localised · endpoint: DFS

Results are not comparable across trials.

Only the 1991 randomised comparison is drawn: the estimated probability of being disease free at five years in patients with Ta or T1 tumours without carcinoma in situ; the abstract gives no confidence interval. The 1976 series had no comparison group. The same trial's carcinoma in situ result, the later BCG-maintenance study (which reports median recurrence-free survival) and the pooled analyses use other populations or measures and are not drawn. BCG in the trial was given both into the bladder and percutaneously. Compare only the two arms of this trial.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

020406080100DFS at 60 months (%)1991lamm-1991-bcg-vs-doxorubicin
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
DFS at 60 months, rate, across 1 trial in this lane. lamm-1991-bcg-vs-doxorubicin (1991): experimental 37 % vs control 17 %.
Data table
TrialYearEndpointControl (%)Experimental (%)
lamm-1991-bcg-vs-doxorubicin1991DFS17 %37 %

Muscle-invasive disease: chemotherapy before definitive local treatment, overall survival

Patients with muscle-invasive bladder cancer (stage T2 to T4a in the cystectomy trial) randomised to platinum-based combination chemotherapy before local treatment or to local treatment alone · Neoadjuvant · endpoint: OS

Results are not comparable across trials.

The two trials tested different regimens (cisplatin, methotrexate and vinblastine in the international trial; MVAC in the US cystectomy trial) and different local treatments: the international trial allowed cystectomy or full-dose radiotherapy, the US trial cystectomy. Both plot median overall survival; neither difference was statistically significant at first report (P = 0.075 and 0.06), the international report had a median follow-up of 4.0 years among survivors, and the US abstract gives no follow-up or hazard ratio. The pooled analysis of ten trials reports a hazard ratio and five-year survival, not medians, and is not drawn. The milestone is flagged needs-review. Compare only each trial's own arms.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

020406080OS, median (months)19991999BA06 30894grossman-neoadjuvant-mvac
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
OS, median, across 2 trials in this lane. BA06 30894 (1999): experimental 44 months vs control 37.5 months; grossman-neoadjuvant-mvac (1999): experimental 77 months vs control 46 months.
Data table
TrialYearEndpointControl (months)Experimental (months)
BA06 308941999OS37.5 months44 months
grossman-neoadjuvant-mvac1999OS46 months77 months

Muscle-invasive disease, cisplatin-eligible: perioperative regimens, event-free survival at 24 months

Adults with muscle-invasive bladder cancer eligible for cisplatin-based chemotherapy and radical cystectomy, randomised to a perioperative regimen or to neoadjuvant gemcitabine-cisplatin followed by cystectomy (NIAGARA, KEYNOTE-B15/EV-304) · Perioperative · endpoint: EFS

Results are not comparable across trials.

Both values are the percentage event-free at 24 months, with gemcitabine-cisplatin before cystectomy as the control. The experimental regimens differ: NIAGARA added durvalumab to gemcitabine-cisplatin and continued durvalumab after surgery, whereas KEYNOTE-B15/EV-304 replaced chemotherapy with enfortumab vedotin plus pembrolizumab before and after surgery. NIAGARA's abstract defines the event as progression, recurrence, not undergoing radical cystectomy, or death; the KEYNOTE-B15 record does not restate the definition. Both abstracts leave the analysis population unstated and follow-up differs (KEYNOTE-B15 reports a median of 33.6 months from randomisation to cut-off). Compare only each trial's own two arms.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

020406080100EFS at 24 months (%)20242026NIAGARAKEYNOTE-B15/EV-304
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
EFS at 24 months, rate, across 2 trials in this lane. NIAGARA (2024): experimental 67.8 % vs control 59.8 %; KEYNOTE-B15/EV-304 (2026): experimental 79.4 % vs control 66.2 %.
Data table
TrialYearEndpointControl (%)Experimental (%)
NIAGARA2024EFS59.8 %67.8 %
KEYNOTE-B15/EV-3042026EFS66.2 %79.4 %

Muscle-invasive disease, cisplatin-ineligible: perioperative therapy versus surgery alone, event-free survival at 24 months

Adults with muscle-invasive bladder cancer ineligible for, or declining, cisplatin-based chemotherapy, randomised to perioperative enfortumab vedotin plus pembrolizumab or to surgery alone (KEYNOTE-905/EV-303) · Perioperative · endpoint: EFS

Results are not comparable across trials.

A single trial is drawn: percentage event-free at 24 months with enfortumab vedotin plus pembrolizumab around surgery versus surgery alone (median follow-up 25.6 months). The control is surgery alone, not chemotherapy, so the result is not comparable with the cisplatin-eligible lane, where the control is gemcitabine-cisplatin. The abstract leaves the analysis population unstated, and the registry record lists a third arm (pembrolizumab with surgery) that this report does not describe. Compare only this trial's own two arms.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

020406080100EFS at 24 months (%)2025KEYNOTE-905/EV-303
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
EFS at 24 months, rate, across 1 trial in this lane. KEYNOTE-905/EV-303 (2025): experimental 74.7 % vs control 39.4 %.
Data table
TrialYearEndpointControl (%)Experimental (%)
KEYNOTE-905/EV-3032025EFS39.4 %74.7 %

Muscle-invasive urothelial cancer after radical surgery: adjuvant nivolumab, disease-free survival

Patients at high risk of recurrence after radical surgery for muscle-invasive urothelial carcinoma, with or without prior neoadjuvant cisplatin-based chemotherapy (CheckMate 274) · Adjuvant · endpoint: DFS

Results are not comparable across trials.

A single trial is drawn: median disease-free survival in the intention-to-treat population, nivolumab for up to one year versus placebo. The result is a median in months, so it is not comparable with the event-free-survival percentages in the perioperative lanes, which also differ in setting and control. The abstract gives a 98.22% confidence interval for the hazard ratio rather than a 95% interval. The milestone is flagged needs-review. Compare only this trial's own two arms.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

0510152025DFS, median (months)2021CheckMate 274
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
DFS, median, across 1 trial in this lane. CheckMate 274 (2021): experimental 20.8 months vs control 10.8 months.
Data table
TrialYearEndpointControl (months)Experimental (months)
CheckMate 2742021DFS10.8 months20.8 months

Advanced urothelial cancer, first-line systemic therapy, overall survival

Adults with advanced or metastatic urothelial cancer who had not received systemic therapy for advanced disease (MVAC versus cisplatin, gemcitabine-cisplatin versus MVAC, enfortumab vedotin plus pembrolizumab versus platinum-based chemotherapy) · Metastatic · endpoint: OS

Results are not comparable across trials.

The control arm changes across eras: single-agent cisplatin (international intergroup trial, 1984 to 1989, 246 assessable patients), MVAC (gemcitabine-cisplatin trial, 405 patients; the plotted medians are its 2005 long-term update, with no significant survival difference) and platinum-based chemotherapy chosen by cisplatin eligibility (EV-302, 886 patients, primary analysis; the 2.5-year update is not drawn). Eligibility, the assessable-patient definition and follow-up differ, and the intergroup abstract gives no hazard ratio or P value for survival. The 1985 single-arm series is not plotted. Compare only each trial's own two arms.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

010203040OS, median (months)198520002023mvac-vs-cisplatin-intergroupgc-vs-mvac-urothelialEV-302
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
OS, median, across 3 trials in this lane. mvac-vs-cisplatin-intergroup (1985): experimental 12.5 months vs control 8.2 months; gc-vs-mvac-urothelial (2000): experimental 14 months vs control 15.2 months; EV-302 (2023): experimental 31.5 months vs control 16.1 months.
Data table
TrialYearEndpointControl (months)Experimental (months)
mvac-vs-cisplatin-intergroup1985OS8.2 months12.5 months
gc-vs-mvac-urothelial2000OS15.2 months14 months
EV-3022023OS16.1 months31.5 months

Advanced urothelial cancer after platinum chemotherapy, overall survival

Adults with locally advanced or metastatic urothelial cancer that progressed after platinum-based chemotherapy, in randomised trials against chemotherapy (KEYNOTE-045, EV-301, IMvigor211, TROPiCS-04) · Metastatic · endpoint: OS

Results are not comparable across trials.

Prior therapy differs: KEYNOTE-045 excluded patients previously given anti-PD-1 or anti-PD-L1 therapy, whereas EV-301 required it; the prior-immunotherapy requirement of TROPiCS-04 is not recorded here. The plotted populations also differ: all randomised patients in KEYNOTE-045 (542), EV-301 (608, interim analysis) and TROPiCS-04 (711, final analysis), but only the PD-L1 immune-cell 5% or more subgroup of IMvigor211 (234 patients), the first group in its hierarchy, where the difference was not significant. The comparator was investigator-chosen chemotherapy in each trial, though the allowed drugs differ. Single-group studies (EV-201, IMvigor210, durvalumab phase 1/2, KEYNOTE-052, TROPHY-U-01) are not plotted. Compare only each trial's own two arms.

Each pair shows one trial: its control arm and its experimental arm. Yesterday's experimental arm is often today's control. Populations, definitions and follow-up differ.

02468101214OS, median (months)2017201920212024KEYNOTE-045EV-301IMvigor211TROPiCS-04
  • experimental arm
  • control arm
  • different endpoint from the lane's
  • step line through experimental values
OS, median, across 4 trials in this lane. KEYNOTE-045 (2017): experimental 10.3 months vs control 7.4 months; EV-301 (2019): experimental 12.88 months vs control 8.97 months; IMvigor211 (2021): experimental 11.1 months vs control 10.6 months; TROPiCS-04 (2024): experimental 10.3 months vs control 9 months.
Data table
TrialYearEndpointControl (months)Experimental (months)
KEYNOTE-0452017OS7.4 months10.3 months
EV-3012019OS8.97 months12.88 months
IMvigor2112021OS10.6 months11.1 months
TROPiCS-042024OS9 months10.3 months

Standard of care, then and now

How the usual sequence of treatment changed for one setting. Choose a point in time; each step links to the milestone behind it.

Advanced urothelial cancer: first-line systemic therapy

Adults with advanced or metastatic urothelial cancer who had not received systemic therapy for advanced disease · Metastatic

  1. Chemotherapy1Gemcitabine plus cisplatinGemcitabine-cisplatin compared with MVAC in advanced bladder cancer (2000)
  2. Antibody–drug conjugate2Enfortumab vedotin plus pembrolizumabEV-302: enfortumab vedotin plus pembrolizumab as first-line (2023)
2024. Based only on the cited trials; practice varies. Enfortumab vedotin plus pembrolizumab was compared with platinum-based chemotherapy in 886 people; FDA regular approval December 2023.
Text version
  • 1995: MVAC
  • 2005: MVAC → Gemcitabine plus cisplatin
  • 2024: Gemcitabine plus cisplatin → Enfortumab vedotin plus pembrolizumab

Muscle-invasive bladder cancer: systemic therapy around local treatment

Adults with muscle-invasive bladder cancer treated with radical cystectomy or, for some, radiotherapy-based bladder preservation · Perioperative

  1. Chemotherapy1Platinum-based chemotherapy before surgeryNeoadjuvant cisplatin-based chemotherapy before cystectomy (1999)
  2. Radiation2Chemoradiotherapy (bladder preservation)BC2001: chemotherapy added to radiotherapy for bladder preservation (2012)
  3. Immunotherapy3Adjuvant nivolumab (high risk)CheckMate 274: adjuvant nivolumab after radical surgery (2021)
  4. Immunotherapy4Durvalumab with gemcitabine-cisplatinNIAGARA: durvalumab added to neoadjuvant gemcitabine-cisplatin (2024)
  5. Antibody–drug conjugate5EV plus pembrolizumab (cisplatin-ineligible)KEYNOTE-905/EV-303: EV plus pembrolizumab around cystectomy (2025)
  6. Antibody–drug conjugate6EV plus pembrolizumab (cisplatin-eligible)KEYNOTE-B15/EV-304: EV-pembrolizumab versus cisplatin-gemcitabine (2026)
2026. Based only on the cited trials; practice varies. FDA approvals: durvalumab with gemcitabine-cisplatin (March 2025); enfortumab vedotin plus pembrolizumab, cisplatin-ineligible (Nov 2025) and cisplatin-eligible (July 2026).
Text version
  • 2005: Platinum-based chemotherapy before surgery
  • 2015: Platinum-based chemotherapy before surgery → Chemoradiotherapy (bladder preservation)
  • 2021: Platinum-based chemotherapy before surgery → Chemoradiotherapy (bladder preservation) → Adjuvant nivolumab (high risk)
  • 2026: Platinum-based chemotherapy before surgery → Chemoradiotherapy (bladder preservation) → Adjuvant nivolumab (high risk) → Durvalumab with gemcitabine-cisplatin → EV plus pembrolizumab (cisplatin-ineligible) → EV plus pembrolizumab (cisplatin-eligible)

Reversals and dead ends

Approaches that were abandoned or withdrawn, and trials whose results were later questioned, are part of the story.

  • 2021

    Atezolizumab and durvalumab urothelial indications withdrawn

    Between 2021 and 2022 the US FDA removed three accelerated approvals for PD-L1 inhibitors in bladder cancer: durvalumab and atezolizumab after platinum chemotherapy, and atezolizumab for people who could not have cisplatin. They had been granted on response-rate data. In the randomised IMvigor211 trial, survival did not differ significantly in the first group tested, people with higher PD-L1.

    FDA accelerated approvals: durvalumab 1 May 2017 (removal letter 19 Feb 2021); atezolizumab post-platinum 18 May 2016 (removal 13 Apr 2021); atezolizumab cisplatin-ineligible 17 Apr 2017 (removal 2 Dec 2022). IMvigor211 (N=931): OS in the PD-L1 IC2/3 group 11.1 vs 10.6 months (HR 0.87; 95% CI 0.63-1.21; P=0.41). IMvigor210 cohort 2: ORR 15% overall.

  • 2024

    Sacituzumab govitecan urothelial indication withdrawn

    In 2021 the FDA granted accelerated approval to sacituzumab govitecan for advanced bladder cancer after platinum chemotherapy and immunotherapy, based on a single-arm study in which about 27 in 100 people responded. In 2024 the indication was withdrawn at the sponsor's request; the FDA letter says the confirmatory randomised trial did not confirm clinical benefit.

    TROPHY-U-01 cohort 1 (phase 2, single-arm, n=113): ORR 27% (95% CI 19.5-36.6), median DOR 7.2 months, median OS 10.9 months. TROPiCS-04 (phase 3, N=711): median OS 10.3 vs 9.0 months (HR 0.86; 95% CI 0.73-1.02; P=0.087); primary endpoint not met. FDA accelerated approval 13 April 2021; voluntary withdrawal 22 November 2024.

Today and tomorrow

Standard of care today

Localised

Non-muscle-invasive bladder cancer (NMIBC). FDA actions read in the approval letters:

  • on 12 June 2025 mitomycin for intravesical solution (Zusduri
  • NDA 215793) for adults with recurrent low-grade intermediate-risk NMIBC
  • for BCG-unresponsive NMIBC, pembrolizumab on 8 January 2020 (BLA 125514/S-066
  • high-risk disease with carcinoma in situ, with or without papillary tumours, in people ineligible for or who have elected not to undergo cystectomy), nadofaragene firadenovec-vncg (Adstiladrin) on 16 December 2022 (CBER
  • STN BL 125700/0
  • adults with high-risk disease with carcinoma in situ, with or without papillary tumours), nogapendekin alfa inbakicept-pmln (Anktiva) with BCG on 22 April 2024 (BLA 761336
  • adults with carcinoma in situ, with or without papillary tumours) and the gemcitabine intravesical system (Inlexzo) on 9 September 2025 (NDA 219683
  • adults with carcinoma in situ, with or without papillary tumours). A supplement for Anktiva (BLA 761336/S-002) was signed on 14 October 2026
  • the indication wording in that letter is Anktiva in combination with BCG for adults with BCG-unresponsive non-muscle invasive bladder cancer and does not include the carcinoma in situ qualifier. Guideline documents are cited by identifier only and their text was not opened, so no recommendation is attributed to them: the 2026 update of the AUA/SUO NMIBC guideline (J Urol, PMID 42689553) and the summary of the 2026 EAU NMIBC guidelines (Eur Urol, PMID 42457459). No FDA or EMA action is stated here for combinations of a checkpoint inhibitor with BCG in BCG-naive disease, because none was read. EMA status for the agents above was not read
U 2025U 2020U 2022U 2024U 2026U 2025Guideline: Clark PE, Holzbeierlein J, Chang SS, Djaladat H, Kim SK, Kirkby E, et al 2026Guideline: Gontero P, Mariappan P, Pradere B, Rai BP, Liedberg F, Compérat E, et al 2026
Perioperative

Muscle-invasive bladder cancer (MIBC) around radical cystectomy. FDA actions read in the approval letters:

  • on 28 March 2025 durvalumab with gemcitabine and cisplatin as neoadjuvant treatment, followed by single-agent durvalumab as adjuvant treatment after radical cystectomy, for adults with MIBC (BLA 761069/S-050)
  • on 21 November 2025 pembrolizumab with enfortumab vedotin as neoadjuvant treatment, continued after cystectomy as adjuvant treatment, for adults with MIBC who are ineligible for cisplatin-containing chemotherapy (BLA 125514/S-188 and BLA 761137/S-032)
  • and on 10 July 2026 the same combination for adults with MIBC (BLA 125514/S-194 and BLA 761137/S-037), where the indication paragraph carries no cisplatin-eligibility wording and the postmarketing-commitment paragraph describes the supporting trial population as eligible for cisplatin-containing chemotherapy. The 28 March 2025 durvalumab letter and the 21 November 2025 pembrolizumab letter list the final overall survival analyses of NIAGARA and of KEYNOTE-905/EV-303 as postmarketing commitments. Guideline documents are cited by identifier only and their text was not opened, so no recommendation is attributed to them: ESMO 2022 (Ann Oncol, PMID 34861372
  • the 2024 interim update covers first-line advanced disease only), NCCN Bladder Cancer version 1.2026 (J Natl Compr Canc Netw, PMID 42140269) and the ASTRO guideline on radiation therapy for bladder cancer (Pract Radiat Oncol 2026, PMID 42744092). EMA status for these regimens was not read
U 2025U 2025U 2025U 2026U 2026Guideline: Powles T, Bellmunt J, Comperat E, De Santis M, Huddart R, Loriot Y, et al 2022Guideline: Flaig TW, Spiess PE, Abern M, An Y, Bangs R, Begovic J, et al 2026Guideline: Ballas LK, Solanki AA, Baumann BC, Dirix P, Hassanzadeh C, Zaorsky NG, et al 2026
Adjuvant
FDA action read in the approval letter: on 19 August 2021 nivolumab (BLA 125554/S-097) for adjuvant treatment of patients with urothelial carcinoma who are at high risk of recurrence after radical resection. The letter's fulfilment section cites 21 CFR 601.41 for earlier commitments under the same application and does not name the indication of that earlier supplement; the adjuvant indication itself carries no accelerated-approval wording. Adjuvant phases are also part of the perioperative regimens listed under that setting. EMA status for nivolumab was not read, and no guideline text was opened.
U 2021
Metastatic

First-line treatment of locally advanced or metastatic urothelial carcinoma. FDA actions read in the approval letters:

  • on 3 April 2023 accelerated approval of pembrolizumab with enfortumab vedotin for people not eligible for cisplatin-containing chemotherapy (BLA 125514/S-136 and BLA 761137/S-018)
  • on 15 December 2023 regular approval for that population following the accelerated approval and expansion to adults with locally advanced or metastatic urothelial cancer (BLA 125514/S-151 and S-152
  • BLA 761137/S-024 and S-025
  • the fulfilment sections cite 21 CFR 601.41 and the letters do not use the word 'converted')
  • and on 6 March 2024 nivolumab with cisplatin and gemcitabine for first-line treatment of adults with unresectable or metastatic urothelial carcinoma (BLA 125554/S-125
  • the letter names a CheckMate 901 substudy). EMA pages read on 20 October 2026: the Keytruda page lists first-line treatment in combination with enfortumab vedotin among its urothelial indications, and the Padcev page shows a marketing authorisation issued on 13 April 2022 (later extensions were not read). EMA status for nivolumab was not read. Guideline documents are cited by identifier only and their text was not opened: the ESMO interim update on first-line therapy in advanced urothelial carcinoma (Ann Oncol 2024, PMID 38490358) and NCCN Bladder Cancer version 1.2026 (PMID 42140269)
FDA 2023FDA 2023FDA 2023FDA 2023U 2024EMA 2026EMA 2022Guideline: Powles T, Bellmunt J, Comperat E, De Santis M, Huddart R, Loriot Y, et al 2024Guideline: Flaig TW, Spiess PE, Abern M, An Y, Bangs R, Begovic J, et al 2026
Maintenance
FDA action read in the approval letter: on 30 June 2020 avelumab (BLA 761049/S-009) for maintenance treatment of locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy. The letter has no accelerated-approval wording for this indication (type 'regular' is an inference) and it also fulfils a postmarketing requirement of the earlier accelerated approval under BLA 761078. The EMA page for Bavencio read on 20 October 2026 lists first-line maintenance treatment of urothelial carcinoma among its indications. No guideline text was opened.
FDA 2020EMA 2020
Relapsed / refractory

Disease that progressed after platinum chemotherapy or immunotherapy. FDA actions read in the approval letters:

  • pembrolizumab on 18 May 2017 for locally advanced or metastatic urothelial carcinoma progressing during or after platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant platinum (BLA 125514/S-018
  • no accelerated-approval wording)
  • enfortumab vedotin by accelerated approval on 18 December 2019 for adults who had received a PD-1 or PD-L1 inhibitor and platinum-containing chemotherapy, with a supplement signed 9 July 2021 that addresses the confirmatory requirement (EV-301) and extends use to people ineligible for cisplatin after at least one prior line
  • and erdafitinib by accelerated approval on 12 April 2019 for susceptible FGFR3 or FGFR2 alterations, followed on 19 January 2024 by regular approval for susceptible FGFR3 alterations after at least one prior line of systemic therapy. EMA pages read on 20 October 2026: Padcev, marketing authorisation issued 13 April 2022
  • Balversa, marketing authorisation issued 22 August 2024 for unresectable or metastatic disease with susceptible FGFR3 alterations after at least one line containing a PD-1 or PD-L1 inhibitor. Four US accelerated approvals were removed (letters of 19 February 2021 for durvalumab, 13 April 2021 and 2 December 2022 for atezolizumab, and a voluntary withdrawal on 22 November 2024 for sacituzumab govitecan, whose letter states that the confirmatory trial did not confirm clinical benefit)
  • the other three letters give no reason, and the EMA Tecentriq page still lists a urothelial monotherapy indication. No guideline text was opened for this setting
FDA 2017FDA 2019FDA 2021EMA 2022FDA 2019FDA 2024EMA 2024FDA 2021FDA 2021FDA 2022FDA 2024EMA 2026FDA 2026

Trials to watch

  • SunRISe-3 NCT05714202

    In BCG-naive high-risk non-muscle-invasive bladder cancer (high-grade Ta, any T1 or carcinoma in situ), does TAR-200 (an intravesical drug-releasing system) with cetrelimab, or TAR-200 alone, improve event-free survival (the registry's primary outcome) compared with intravesical BCG? Registry record: randomised, open-label phase 3, 1,135 enrolled (actual), sponsor Janssen Research & Development. Registry status: active, not recruiting; registry primary completion date 2029-09 (listed as estimated; the record was last updated 2026-09-25); no results posted.

  • BRIDGE (EA8212) NCT05538663

    In BCG-naive high-grade non-muscle-invasive bladder cancer, is intravesical gemcitabine plus docetaxel non-inferior to intravesical BCG for event-free survival (the registry's primary outcome, with a registry time frame of 2 years)? Registry record: randomised, open-label phase 3, 870 estimated, sponsor ECOG-ACRIN Cancer Research Group. Registry status: active, not recruiting; registry primary completion date 2029-11 (estimated; the record was last updated 2026-09-15); no results posted. The registry summary states the hypothesis of non-inferiority.

  • SWOG S1806 NCT03775265

    In localized muscle-invasive urothelial carcinoma (T2 to T4a, N0, M0) treated with bladder-preserving chemoradiotherapy, does adding atezolizumab improve bladder-intact event-free survival (the registry's primary outcome)? Registry record: randomised, open-label phase 3, 475 estimated, sponsor National Cancer Institute (NCI). Registry status: active, not recruiting; registry primary completion date 2027-06 (estimated; the record was last updated 2026-08-28); no results posted.

  • KEYNOTE-992 NCT04241185

    In muscle-invasive bladder cancer (N0 M0, predominantly urothelial histology) planned for chemoradiotherapy, does pembrolizumab added to chemoradiotherapy improve bladder-intact event-free survival (the registry's primary outcome) compared with placebo plus chemoradiotherapy? Registry record: randomised phase 3 with a placebo comparator (the chemoradiotherapy is open-label), 520 estimated, sponsor Merck Sharp & Dohme LLC. Registry status: active, not recruiting; registry primary completion date 2027-01 (estimated; the record was last updated 2026-05-01); no results posted.

  • KEYNOTE-676 NCT03711032

    In high-risk non-muscle-invasive bladder cancer, does pembrolizumab added to BCG differ from BCG alone in complete response rate by blinded independent central review (the registry's primary outcome for cohort A, persistent or recurrent disease after BCG induction) and in event-free survival (the primary outcome for cohort B, BCG-naive)? Registry record: randomised, open-label phase 3, 1,397 estimated, sponsor Merck Sharp & Dohme LLC. Registry status: active, not recruiting; registry primary completion date 2026-07 (listed as estimated and already past on 21 October 2026; the record was last updated 2026-05-01); no results posted.

  • SGNDV-001 (DV-001) NCT05911295

    In previously untreated locally advanced unresectable or metastatic urothelial carcinoma that expresses HER2 (immunohistochemistry 1+ or greater) and is eligible for platinum chemotherapy, does disitamab vedotin plus pembrolizumab improve progression-free survival by blinded independent central review and overall survival (the registry's two primary outcomes) compared with gemcitabine plus cisplatin or carboplatin? Registry record: randomised, open-label phase 3, 412 enrolled (actual), sponsor Seagen, a wholly owned subsidiary of Pfizer. Registry status: active, not recruiting; registry primary completion date 2027-01 (estimated; the record was last updated 2026-07-22); no results posted. A design paper for the trial (Future Oncology 2025, PMID 40728126) has been published; it reports no results.

Pioneers

References

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Every figure was checked against its primary source to the extent possible. Items that could not be fully confirmed are marked “needs review”. Educational history, not medical advice.

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2021TreatmentImmunotherapy

majorAdjuvantNeeds review

CheckMate 274: adjuvant nivolumab after radical surgery

After surgery for high-risk muscle-invasive urothelial cancer, up to a year of nivolumab was compared with placebo. Median time free of disease was about 21 months with nivolumab and 11 months with placebo. Severe (grade 3 or higher) treatment-related side effects were more frequent with nivolumab. The FDA approved adjuvant nivolumab in August 2021.

CheckMate 274 (phase 3, double-blind, n=709): adjuvant nivolumab 240 mg every 2 weeks for up to 1 year vs placebo after radical surgery. ITT median DFS 20.8 vs 10.8 months; 6-month DFS 74.9% vs 60.3%; HR 0.70 (98.22% CI 0.55-0.90, P<0.001). PD-L1 1% or more: 6-month 74.5% vs 55.7%, HR 0.55 (98.72% CI 0.35-0.85). Grade 3 or higher treatment-related adverse events 17.9% vs 7.2%. FDA approval 19 August 2021.

Standard before

According to the trial abstract, the role of adjuvant treatment in high-risk muscle-invasive urothelial carcinoma after radical surgery was not clear; the control in the trial was placebo.

What changed

On 19 August 2021 the FDA approved nivolumab for the adjuvant treatment of patients with urothelial carcinoma at high risk of recurrence after radical resection.

Why it mattered

It was a placebo-controlled phase 3 trial in which disease-free survival was longer with adjuvant nivolumab than with placebo, in the intention-to-treat population (HR 0.70) and in patients with PD-L1 expression of 1% or more (HR 0.55).

Caveats

  • The abstract reports disease-free survival and survival free from recurrence outside the urothelial tract; it gives no overall survival result.
  • The hazard ratios for the primary end points are reported with 98.22% and 98.72% confidence intervals, not 95% intervals.
  • Treatment-related adverse events of grade 3 or higher occurred in 17.9% with nivolumab and 7.2% with placebo, and two treatment-related deaths due to pneumonitis occurred in the nivolumab group.
  • The trial enrolled patients with urothelial carcinoma originating in the bladder, ureter or renal pelvis (upper-tract enrolment was capped at about 20%), with or without neoadjuvant cisplatin-based chemotherapy before entry; the registry title likewise refers to bladder or upper urinary tract cancer. Check the population against other adjuvant trials before comparing DFS values.