Defining safe bladder preservation in BCG-unresponsive high-risk non-muscle-invasive bladder cancer: beyond complete response
- 1Second Department of Urology, The First Affiliated Hospital of Kunming Medical University
Abstract
Bacillus Calmette-Guerin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (NMIBC) remains a challenging disease state in which radical cystectomy (RC) provides the most reliable oncologic control, while an expanding range of bladder-preserving therapies offers alternatives for patients who decline or are unfit for surgery. We critically reviewed PubMed/MEDLINE, international guidelines, pivotal and late-phase trials, long-term follow-up studies, regulatory summaries, systematic reviews, and multicenter real-world studies through 30 September 2026, prioritizing evidence relevant to patient selection, response durability, progression risk, salvage RC, treatment burden, and patient-reported outcomes. Pembrolizumab, nadofaragene firadenovec, nogapendekin alfa inbakicept plus BCG, the gemcitabine intravesical system (TAR-200), oncolytic viral approaches, FGFR-directed therapy, and sequential intravesical gemcitabine/docetaxel have broadened treatment options in this setting. However, cross-trial comparisons based on a single 3- or 6-month complete response are potentially misleading because disease phenotype, response definitions, surveillance intensity, biopsy requirements, treatment duration, and failure management differ substantially across studies; for most platforms, cross-trial efficacy estimates should therefore be interpreted descriptively rather than as head-to-head comparisons. We propose an author-derived, non-validated hierarchical framework in which clinically meaningful bladder preservation integrates phenotype-matched early tumor clearance, 12- to 24-month response durability, high-grade recurrence-free survival, freedom from muscle-invasive or metastatic progression, the timing and pathologic outcomes of subsequent RC, and treatment burden. This framework is intended to organize clinical interpretation rather than function as a validated score, guideline, or consensus recommendation. Persistent or recurrent high-grade disease, particularly T1 recurrence or suspected progression, should prompt restaging and renewed discussion of RC. Bladder preservation should thus be regarded as a time-limited, closely monitored management strategy with explicit entry criteria and stopping rules. Its success should be defined by durable high-grade disease control without compromising the opportunity for curative salvage RC, rather than by preservation of the bladder alone.
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BibTeX
@article{chen2026defining,
title = {{Defining safe bladder preservation in BCG-unresponsive high-risk non-muscle-invasive bladder cancer: beyond complete response}},
author = {Chaohu Chen and Botao Xie and Cheng Chen and Peng Gu and Xinan Chen},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1983996},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1983996/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Defining safe bladder preservation in BCG-unresponsive high-risk non-muscle-invasive bladder cancer: beyond complete response
AU - Chaohu Chen
AU - Botao Xie
AU - Cheng Chen
AU - Peng Gu
AU - Xinan Chen
PY - 2026
DA - 2026/10/22
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1983996
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1983996/full
AB - Bacillus Calmette-Guerin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (NMIBC) remains a challenging disease state in which radical cystectomy (RC) provides the most reliable oncologic control, while an expanding range of bladder-preserving therapies offers alternatives for patients who decline or are unfit for surgery. We critically reviewed PubMed/MEDLINE, international guidelines, pivotal and late-phase trials, long-term follow-up studies, regulatory summaries, systematic reviews, and multicenter real-world studies through 30 September 2026, prioritizing evidence relevant to patient selection, response durability, progression risk, salvage RC, treatment burden, and patient-reported outcomes. Pembrolizumab, nadofaragene firadenovec, nogapendekin alfa inbakicept plus BCG, the gemcitabine intravesical system (TAR-200), oncolytic viral approaches, FGFR-directed therapy, and sequential intravesical gemcitabine/docetaxel have broadened treatment options in this setting. However, cross-trial comparisons based on a single 3- or 6-month complete response are potentially misleading because disease phenotype, response definitions, surveillance intensity, biopsy requirements, treatment duration, and failure management differ substantially across studies; for most platforms, cross-trial efficacy estimates should therefore be interpreted descriptively rather than as head-to-head comparisons. We propose an author-derived, non-validated hierarchical framework in which clinically meaningful bladder preservation integrates phenotype-matched early tumor clearance, 12- to 24-month response durability, high-grade recurrence-free survival, freedom from muscle-invasive or metastatic progression, the timing and pathologic outcomes of subsequent RC, and treatment burden. This framework is intended to organize clinical interpretation rather than function as a validated score, guideline, or consensus recommendation. Persistent or recurrent high-grade disease, particularly T1 recurrence or suspected progression, should prompt restaging and renewed discussion of RC. Bladder preservation should thus be regarded as a time-limited, closely monitored management strategy with explicit entry criteria and stopping rules. Its success should be defined by durable high-grade disease control without compromising the opportunity for curative salvage RC, rather than by preservation of the bladder alone.
SN - 1664-3224
ER -