Optimal timing of adjuvant immunotherapy after radical cystectomy in muscle-invasive bladder cancer: from calendar-based to MRD-guided decision making
- 1Hematology Oncology Department, Saint Joseph University of Beirut
Abstract
The approval of adjuvant nivolumab and pembrolizumab following radical cystectomy and more recently perioperative durvalumab-based strategies represents a significant therapeutic advance in muscle-invasive bladder cancer (MIBC). However, a question that has received limited systematic attention concerns the optimal timing of immunotherapy initiation after surgery. Current recommendations are derived entirely from the eligibility windows of pivotal clinical trials, most notably CheckMate 274, AMBASSADOR and NIAGARA, which mandated randomization within approximately 120 days of cystectomy. These operational thresholds were designed to ensure postoperative recovery and were not prospectively validated as biologically optimal. This review critically examines the biological rationale underpinning timing considerations, appraises what clinical trials have actually studied, draws cautious parallels with adjuvant chemotherapy literature, and discusses how circulating tumour DNA (ctDNA) and minimal residual disease (MRD) detection may eventually redefine timing decisions. We conclude that no validated therapeutic window currently exists, that available evidence supports initiation within the studied timeframe when clinically feasible, and that prospective timing analyzes constitute a major unmet need in MIBC research.
Related
- FGFR3 Gene Alterations and Protein Expression in Paired TURBT and Radical Cystectomy Archival Specimens of Muscle-Invasive Bladder Cancer.
- Prognostic Impact of Nectin4 and IRF6 Expression in Patients Undergoing Radical Cystectomy for Muscle-Invasive Bladder Cancer.
- Predicting acute kidney injury after radical cystectomy for muscle-invasive bladder cancer.
- Bladder metastasis from cutaneous melanoma during adjuvant immunotherapy: A case report and literature review
- [Evolution of Perioperative Immunotherapy Paradigms in Non-small Cell Lung Cancer: From Adjuvant Dilemma to Neoadjuvant Priority].
BibTeX
@article{naim2026optimal,
title = {{Optimal timing of adjuvant immunotherapy after radical cystectomy in muscle-invasive bladder cancer: from calendar-based to MRD-guided decision making}},
author = {Nabih Naim and Ahmad Saad and Nesrine Mohamad and Joseph Kattan},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1933232},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1933232/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Optimal timing of adjuvant immunotherapy after radical cystectomy in muscle-invasive bladder cancer: from calendar-based to MRD-guided decision making
AU - Nabih Naim
AU - Ahmad Saad
AU - Nesrine Mohamad
AU - Joseph Kattan
PY - 2026
DA - 2026/10/21
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1933232
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1933232/full
AB - The approval of adjuvant nivolumab and pembrolizumab following radical cystectomy and more recently perioperative durvalumab-based strategies represents a significant therapeutic advance in muscle-invasive bladder cancer (MIBC). However, a question that has received limited systematic attention concerns the optimal timing of immunotherapy initiation after surgery. Current recommendations are derived entirely from the eligibility windows of pivotal clinical trials, most notably CheckMate 274, AMBASSADOR and NIAGARA, which mandated randomization within approximately 120 days of cystectomy. These operational thresholds were designed to ensure postoperative recovery and were not prospectively validated as biologically optimal. This review critically examines the biological rationale underpinning timing considerations, appraises what clinical trials have actually studied, draws cautious parallels with adjuvant chemotherapy literature, and discusses how circulating tumour DNA (ctDNA) and minimal residual disease (MRD) detection may eventually redefine timing decisions. We conclude that no validated therapeutic window currently exists, that available evidence supports initiation within the studied timeframe when clinically feasible, and that prospective timing analyzes constitute a major unmet need in MIBC research.
SN - 2234-943X
ER -