ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Genomic Tumor Correlates of Clinical Outcomes Following Organ-Sparing Chemoradiation Therapy for Bladder Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 14 citations in OpenAlex.
- A ferroptosis-suppressive state drives resistance to bladder-preserving chemoradiotherapy in muscle-invasive bladder cancer.Signal transduction and targeted therapy · 2026Article
- Optimizing local control in the surgical management of bladder cancer.Nature reviews. Urology · 2026Review
- A luminal non-coding RNA-based genomic classifier confirms favourable outcomes in patients with clinically organ-confined bladder cancer treated with radical cystectomy.BJU international · 2025Article
- Article
- ATM deficiency confers specific therapeutic vulnerabilities in bladder cancer.Science advances · 2023Article
- Bladder cancer.Nature reviews. Disease primers · 2023Review
- Impact of DNA repair deficiency on sensitivity to antibody-drug conjugate (ADC) payloads in bladder cancer.Bladder cancer (Amsterdam, Netherlands)Article
- The importance of maximal TURBT in trimodality therapy for muscle-invasive bladder cancer (MIBC).Bladder cancer (Amsterdam, Netherlands)Review
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Authors and funding
22 authors at 7 institutions in 1 country.
Funding
Abstract
purposeThere is an urgent need for biomarkers of radiation response in organ-sparing therapies. Bladder preservation with trimodality therapy (TMT), consisting of transurethral tumor resection followed by chemoradiation, is an alternative to radical cystectomy for muscle-invasive bladder cancer (MIBC), but molecular determinants of response are poorly understood. EXPERIMENTAL
designWe characterized genomic and transcriptomic features correlated with long-term response in a single institution cohort of patients with MIBC homogeneously treated with TMT. Pretreatment tumors from 76 patients with MIBC underwent whole-exome sequencing; 67 underwent matched transcriptomic profiling. Molecular features were correlated with clinical outcomes including modified bladder-intact event-free survival (mBI-EFS), a composite endpoint that reflects long-term cancer control with bladder preservation.
resultsWith a median follow-up of 74.6 months in alive patients, 37 patients had favorable long-term response to TMT while 39 had unfavorable long-term response. Tumor mutational burden was not associated with outcomes after TMT. DNA damage response gene alterations were associated with improved locoregional control and mBI-EFS. Of these alterations, somatic ERCC2 mutations stood out as significantly associated with favorable long-term outcomes; patients with ERCC2 mutations had significantly improved mBI-EFS [HR, 0.15; 95% confidence interval (CI), 0.06-0.37; P = 0.030] and improved BI-EFS, an endpoint that includes all-cause mortality (HR, 0.33; 95% CI, 0.15-0.68; P = 0.044). ERCC2 mutant bladder cancer cell lines were significantly more sensitive to concurrent cisplatin and radiation treatment in vitro than isogenic ERCC2 wild-type cells.
conclusionsOur data identify ERCC2 mutation as a candidate biomarker associated with sensitivity and long-term response to chemoradiation in MIBC. These findings warrant validation in independent cohorts.
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