The Surveillance, Epidemiology, and End Results (SEER) Program. Cancer stat facts: bladder cancer 2024. Available from: https://seer.cancer.gov/statfacts/html/urinb.html.

Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin. 2025;75(1):10.

PubMed  PubMed Central  Google Scholar 

Patel VG, Oh WK, Galsky MD. Treatment of muscle-invasive and advanced bladder cancer in 2020. CA Cancer J Clin. 2020;70(5):404–23.

PubMed  Google Scholar 

Tian J, Sun J, Fu G, Xu Z, Chen X, Shi Y, et al. Population-based outcome of muscle-invasive bladder cancer following radical cystectomy: who can benefit from adjuvant chemotherapy? Transl Androl Urol. 2021;10(1):356–73.

Article  PubMed  PubMed Central  Google Scholar 

Park JC, Citrin DE, Agarwal PK, Apolo AB. Multimodal management of muscle-invasive bladder cancer. Curr Probl Cancer. 2014;38(3):80–108.

Article  CAS  PubMed  PubMed Central  Google Scholar 

von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005;23(21):4602–8.

Article  PubMed  Google Scholar 

Stein JP, Lieskovsky G, Cote R, Groshen S, Feng A-C, Boyd S, et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1054 patients. J Clin Oncol. 2023;41(22):3772–81.

Article  PubMed  Google Scholar 

Roviello G, Catalano M, Santi R, Santoni M, Galli IC, Amorosi A, et al. Neoadjuvant treatment in muscle-invasive bladder cancer: from the beginning to the latest developments. Front Oncol. 2022;12:912699.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kamat AM, Apolo AB, Babjuk M, Bivalacqua TJ, Black PC, Buckley R, et al. Definitions, end points, and clinical trial designs for bladder cancer: recommendations from the society for immunotherapy of cancer and the international bladder cancer group. J Clin Oncol. 2023;41(35):5437.

Article  PubMed  PubMed Central  Google Scholar 

Advanced Bladder Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur Urol. 2005;48(2):202–5 (discussion 5-6).

Article  Google Scholar 

Dash A, Galsky MD, Vickers AJ, Serio AM, Koppie TM, Dalbagni G, et al. Impact of renal impairment on eligibility for adjuvant cisplatin-based chemotherapy in patients with urothelial carcinoma of the bladder. Cancer. 2006;107(3):506–13.

Article  CAS  PubMed  Google Scholar 

Galsky MD, Hahn NM, Rosenberg J, Sonpavde G, Hutson T, Oh WK, et al. Treatment of patients with metastatic urothelial cancer “unfit” for cisplatin-based chemotherapy. J Clin Oncol. 2011;29(17):2432–8.

Article  PubMed  Google Scholar 

Gupta S, Powles T, Kearney M, Panattoni L, Land N, Flottemesch T, et al. Criteria used to determine platinum eligibility in patients with metastatic urothelial carcinoma: results of a physician survey in five European countries. Eur Urol Open Sci. 2025;81:28–36.

Article  PubMed  PubMed Central  Google Scholar 

Lan T, Ran S, Gao M, Li W, He W. A narrative review of management of muscle-invasive bladder cancer perioperative period: will continuous and combined treatment be the new trend? Transl Androl Urol. 2024;13(2):293.

Article  PubMed  PubMed Central  Google Scholar 

Sonpavde G, Necchi A, Gupta S, Steinberg GD, Gschwend JE, Van Der Heijden MS, et al. ENERGIZE: a Phase III study of neoadjuvant chemotherapy alone or with nivolumab with/without linrodostat mesylate for muscle-invasive bladder cancer. Future Oncol. 2020;16(02):4359–68.

Article  CAS  PubMed  Google Scholar 

Hoimes CJ, Bedke J, Loriot Y, Nishiyama H, Fang X, Kataria RS, et al. KEYNOTE-B15/EV-304: randomized phase 3 study of perioperative enfortumab vedotin plus pembrolizumab versus chemotherapy in cisplatin-eligible patients with muscle-invasive bladder cancer (MIBC). J Clin Oncol. 2021;39:TPS4587.

Article  Google Scholar 

Necchi A, Anichini A, Raggi D, Briganti A, Massa S, Lucianò R, et al. Pembrolizumab as neoadjuvant therapy before radical cystectomy in patients with muscle-invasive urothelial bladder carcinoma (PURE-01): an open-label, single-arm, phase II study. J Clin Oncol. 2018;36(34):3353–60.

Article  CAS  PubMed  Google Scholar 

Perioperative pembrolizumab (MK-3475) plus neoadjuvant chemotherapy versus perioperative placebo plus neoadjuvant chemotherapy for cisplatin-eligible muscle-invasive bladder cancer (MIBC) (MK-3475-866/KEYNOTE-866) (KEYNOTE-866) [cited 2024 March 6]. Available from: https://clinicaltrials.gov/ct2/show/NCT03924856.

Powles T, Meeks JJ, Galsky MD, Van Der Heijden MS, Nishiyama H, Al-Ahmadie HA, et al. A phase III, randomized, open-label, multicenter, global study of efficacy and safety of durvalumab in combination with gemcitabine plus cisplatin for neoadjuvant treatment followed by durvalumab alone for adjuvant treatment in muscle-invasive bladder cancer (NIAGARA). J Clin Oncol. 2021;39:TPS505.

Article  Google Scholar 

Perioperative enfortumab vedotin (EV) plus pembrolizumab (MK-3475) versus neoadjuvant chemotherapy for cisplatin-eligible muscle invasive bladder cancer (MIBC) (MK-3475-B15/KEYNOTE-B15/EV-304) [cited 2024 March 6]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT04700124.

U.S. Food and Drug Administration. Clinical trial endpoints for the approval of cancer drugs and biologics guidance for industry 2018 [cited 2024 March 14]. Available from: https://www.fda.gov/media/71195/download.

Ciani O, Buyse M, Drummond M, Rasi G, Saad ED, Taylor RS. Time to review the role of surrogate end points in health policy: state of the art and the way forward. Value Health. 2017;20(3):487–95.

Article  PubMed  Google Scholar 

Prasad V, Kim C, Burotto M, Vandross A. The strength of association between surrogate end points and survival in oncology: a systematic review of trial-level meta-analyses. JAMA Intern Med. 2015;175(8):1389–98.

Article  PubMed  Google Scholar 

Powles T, Drakaki A, Teoh JY-C, Grande E, Fontes-Sousa M, Porta C et al. A phase 3, randomized, open-label, multicenter, global study of the efficacy and safety of durvalumab (D)+ tremelimumab (T)+ enfortumab vedotin (EV) or D+ EV for neoadjuvant treatment in cisplatin-ineligible muscle-invasive bladder cancer (MIBC)(VOLGA). J Clin Oncol. 2022;40:TPS579–TPS579.

Article  Google Scholar 

Delgado A, Guddati AK. Clinical endpoints in oncology—a primer. Am J Cancer Res. 2021;11(4):1121–31.

PubMed  PubMed Central  Google Scholar 

Finnbladder NBCSG, de Tratamiento Oncologico CUE, Group EG-U, Group ABCS, Group NCIoCCT. Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. The Lancet. 1999;354(9178):533–40.

Article  Google Scholar 

International Collaboration of Trialists, Finnbladder NBCSG, de Tratamiento Oncologico CUE, Group ABCS, Group NCIoCCT. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol. 2011;29(16):2171.

Article  Google Scholar 

Koie T, Ohyama C, Hashimoto Y, Hatakeyama S, Yamamoto H, Yoneyama T, et al. Efficacies and safety of neoadjuvant gemcitabine plus carboplatin followed by immediate cystectomy in patients with muscle-invasive bladder cancer, including those unfit for cisplatin: a prospective single-arm study. Int J Clin Oncol. 2013;18:724–30.

Article  CAS  PubMed  Google Scholar 

Kitamura H, Tsukamoto T, Shibata T, Masumori N, Fujimoto H, Hirao Y, et al. Randomised phase III study of neoadjuvant chemotherapy with methotrexate, doxorubicin, vinblastine and cisplatin followed by radical cystectomy compared with radical cystectomy alone for muscle-invasive bladder cancer: Japan Clinical Oncology Group Study JCOG0209. Ann Oncol. 2014;25(6):1192–8.

Article  CAS  PubMed  Google Scholar 

Osman MA, Gabr AM, Elkady MS. Neoadjuvant chemotherapy versus cystectomy in management of stages II, and III urinary bladder cancer. Arch Ital Urol Androl. 2014;86(4):278–83.

Article  PubMed  Google Scholar 

Anari F, O’Neill J, Choi W, Chen DY, Haseebuddin M, Kutikov A, et al. Neoadjuvant dose-dense gemcitabine and cisplatin in muscle-invasive bladder cancer: results of a phase 2 trial. Eur Urol Oncol. 2018;1(1):54–60.

Article  PubMed  PubMed Central  Google Scholar 

Iyer G, Balar AV, Milowsky MI, Bochner BH, Dalbagni G, Donat SM, et al. Multicenter prospective phase II trial of neoadjuvant dose-dense gemcitabine plus cisplatin in patients with muscle-invasive bladder cancer. J Clin Oncol. 2018;36(19):1949.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Challapalli A, Masson S, White P, Dailami N, Pearson S, Rowe E, et al. A single-arm phase II trial of neoadjuvant cabazitaxel and cisplatin chemotherapy for muscle-invasive transitional cell carcinoma of the urinary bladder. Clin Genitourin Cancer. 2021;19(4):325–32.

Article  PubMed  Google Scholar 

Flaig TW, Tangen CM, Daneshmand S, Alva A, Lerner SP, Lucia MS, et al. A randomized phase II study of coexpression extrapolation (COXEN) with neoadjuvant chemotherapy for bladder cancer (SWOG S1314; NCT02177695). Clin Cancer Res. 2021;27(9):2435–41.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shi H, Zhang W, Bi X, Wang D, Xiao Z, Guan Y, et al. Neoadjuvant chemotherapy-guided bladder-sparing treatment for muscle-invasive bladder cancer: results of a pilot phase II study. Cancer Res