Navigating the current and future perioperative treatment landscape of muscle-invasive bladder cancer (MIBC).
- 1Hematology/Oncology, Inova Schar Cancer Institute, Fairfax, VA, USA.
- 2GU Medical Oncology, Inova Schar Cancer Institute, Fairfax, VA, USA.
Abstract
Muscle-invasive bladder cancer (MIBC) carries a high risk of recurrence after radical cystectomy, prompting rapid evolution of perioperative systemic therapy. Cisplatin-based neoadjuvant chemotherapy (NAC) was the previous prevailing standard treatment supported by randomized data and optimized through regimen refinement, including dose-dense methotrexate, vinblastine, doxorubicin (adriamycin), cisplatin (ddMVAC) and gemcitabine/cisplatin (GC). However, cisplatin-eligibility limits the ability to deliver effective NAC. More recently, chemoimmunotherapy has advanced with perioperative durvalumab demonstrating improvements in event-free and overall survival (OS), raising questions about optimal sequencing and patient selection. Antibody-drug conjugate strategies, particularly perioperative enfortumab vedotin plus pembrolizumab (EVP), have further broadened options for both cisplatin-eligible and -ineligible patients. The use of EVP in the EV-304 trial yielded a 2-year event-free survival of 79.4% with EVP compared to 66.2% with GC, with improvement of pathological complete response of 55.8% in EVP and 32.5% for the GC (P<0.001), which has changed the landscape of treatment of MIBC. Despite all of these improvements, there remain critical questions including the added benefit of adjuvant immunotherapy, the utility of circulating tumor DNA (ctDNA), the number of perioperative cycles required to achieve the optimal response, surrogacy of pathologic complete response (pCR) to OS, added toxicity of these perioperative regimens, and ultimate need for radical cystectomy in those who achieve pCR, as well as lack of comparison to other alternative trimodality regimens. This mini-review summarizes pivotal trials and ongoing controversies shaping contemporary MIBC care.
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BibTeX
@article{azad2026navigating,
title = {{Navigating the current and future perioperative treatment landscape of muscle-invasive bladder cancer (MIBC).}},
author = {Farhan Azad and Eseoghene Kevu and Jeanny B Aragon-Ching},
journal = {Translational cancer research},
year = {2026},
month = oct,
doi = {10.21037/tcr-2026-1823},
url = {https://europepmc.org/article/MED/42997899},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Navigating the current and future perioperative treatment landscape of muscle-invasive bladder cancer (MIBC).
AU - Farhan Azad
AU - Eseoghene Kevu
AU - Jeanny B Aragon-Ching
PY - 2026
DA - 2026/10/26
JO - Translational cancer research
DO - 10.21037/tcr-2026-1823
UR - https://europepmc.org/article/MED/42997899
AB - Muscle-invasive bladder cancer (MIBC) carries a high risk of recurrence after radical cystectomy, prompting rapid evolution of perioperative systemic therapy. Cisplatin-based neoadjuvant chemotherapy (NAC) was the previous prevailing standard treatment supported by randomized data and optimized through regimen refinement, including dose-dense methotrexate, vinblastine, doxorubicin (adriamycin), cisplatin (ddMVAC) and gemcitabine/cisplatin (GC). However, cisplatin-eligibility limits the ability to deliver effective NAC. More recently, chemoimmunotherapy has advanced with perioperative durvalumab demonstrating improvements in event-free and overall survival (OS), raising questions about optimal sequencing and patient selection. Antibody-drug conjugate strategies, particularly perioperative enfortumab vedotin plus pembrolizumab (EVP), have further broadened options for both cisplatin-eligible and -ineligible patients. The use of EVP in the EV-304 trial yielded a 2-year event-free survival of 79.4% with EVP compared to 66.2% with GC, with improvement of pathological complete response of 55.8% in EVP and 32.5% for the GC (P<0.001), which has changed the landscape of treatment of MIBC. Despite all of these improvements, there remain critical questions including the added benefit of adjuvant immunotherapy, the utility of circulating tumor DNA (ctDNA), the number of perioperative cycles required to achieve the optimal response, surrogacy of pathologic complete response (pCR) to OS, added toxicity of these perioperative regimens, and ultimate need for radical cystectomy in those who achieve pCR, as well as lack of comparison to other alternative trimodality regimens. This mini-review summarizes pivotal trials and ongoing controversies shaping contemporary MIBC care.
SN - 2218-676X
SN - 2219-6803
ER -