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Review
. 2025 Apr 25;11(2):23523735251335122.
doi: 10.1177/23523735251335122. eCollection 2025 Apr-Jun.

Advancements in systemic therapy for muscle-invasive bladder cancer: A systematic review from the beginning to the latest updates

Takafumi Yanagisawa  1   2 , Akihiro Matsukawa  1   2 , Jeremy Yuen-Chun Teoh  2   3 , Keiichiro Mori  1   2 , Tatsushi Kawada  2   4 , Satoshi Katayama  2   4 , Paweł Rajwa  2   5 , Fahad Quhal  2   6 , Benjamin Pradere  2   7 , Marco Moschini  8 , Shahrokh F Shariat  2   9   10   11   12   13   14 , Jun Miki  1 , Takahiro Kimura  1
Affiliations
Review

Advancements in systemic therapy for muscle-invasive bladder cancer: A systematic review from the beginning to the latest updates

Takafumi Yanagisawa et al. Bladder Cancer. .

Abstract

Context: Several phase III randomized controlled trials (RCTs) have shown the importance of perioperative systemic therapy, especially for the efficacy of immune checkpoint inhibitors (ICIs) in both neoadjuvant and adjuvant settings for muscle-invasive bladder cancer (MIBC).

Objective: To synthesize the growing evidence on the efficacy and safety of systemic therapies for MIBC utilizing the data from RCTs.

Evidence acquisition: Three databases and ClinicalTrials.gov were searched in October 2024 for eligible RCTs evaluating oncologic outcomes in MIBC patients treated with systemic therapy. We evaluated pathological complete response (pCR), disease-free survival (DFS), progression-free survival (PFS), event-free survival (EFS), overall survival (OS), and adverse events (AEs).

Evidence synthesis: Thirty-three RCTs (including 14 ongoing trials) were included in this systematic review. Neoadjuvant chemotherapy improved OS compared to radical cystectomy alone. Particularly, the VESPER trial demonstrated that dd-MVAC provided oncological benefits over GC alone in terms of pCR rates, OS (HR: 0.71), and PFS (HR: 0.70). Recently, the NIAGARA trial showed that perioperative durvalumab plus GC outperformed GC alone in terms of pCR rates, OS (HR: 0.75), and EFS (HR: 0.68). Despite the lack of data on overall AE rates in the VESPER trial, differential safety profiles in hematologic toxicity were reported between dd-MVAC and durvalumab plus GC regimens. In the adjuvant setting, no study provided the OS benefit from adjuvant chemotherapy. However, only adjuvant nivolumab had significant DFS and OS benefits compared to placebo.

Conclusions: Neoadjuvant chemotherapy remains the current standard of care for MIBC. Durvalumab shed light on the promising impact of ICIs added to neoadjuvant chemotherapy. Nivolumab is the only ICI recommended as adjuvant therapy in patients who harbored adverse pathologic outcomes. Ongoing trials will provide further information on the impact of combination therapy, including chemotherapy, ICIs, and enfortumab vedotin, in both neoadjuvant and adjuvant settings.

Keywords: adjuvant; chemotherapy; immune checkpoint inhibitors; muscle-invasive; neoadjuvant; urothelial carcinoma.

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Figures

Figure 1.
Figure 1.
PRISMA 2020 flow diagram for systematic reviews which included searches of databases, registers and other sources
Figure 2.
Figure 2.
Current treatment strategy for MIBC
See this image and copyright information in PMC

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