Natural History and Genomic Landscape of Chemotherapy-Resistant Muscle-Invasive Bladder Cancer.

Autor:	Lenis AT; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY.; Department of Urology, Columbia University Irving Medical Center, New York, NY., Whiting K; Biostatistics Service, Department of Epidemiology & Biostatistics, MSK, New York, NY., Ravichandran V; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, MSK, New York, NY., Tallman JE; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY., Alam SM; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY., Chu CE; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY., Jesus Escano M; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY., Bochner E; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY., Katims A; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY., Reisz PA; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY., Truong H; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY., Clinton TN; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY., Telis L; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY., Dason S; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY., McPherson V; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY., Teo MY; Genitourinary Oncology Service, Department of Medicine, MSK, New York, NY., Funt S; Genitourinary Oncology Service, Department of Medicine, MSK, New York, NY., Aggen D; Genitourinary Oncology Service, Department of Medicine, MSK, New York, NY., Goh AC; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY., Donahue TF; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY., Cha EK; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY., Donat SM; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY., Herr HW; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY., Dalbagni G; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY., Schultz N; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, MSK, New York, NY.; Computational Oncology Service, Department of Epidemiology & Biostatistics, MSK, New York, NY.; Human Oncology and Pathogenesis Program, MSK, New York, NY., Berger MF; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, MSK, New York, NY.; Human Oncology and Pathogenesis Program, MSK, New York, NY.; Molecular Diagnostics Service, Department of Pathology, MSK, New York, NY., Bajorin DF; Genitourinary Oncology Service, Department of Medicine, MSK, New York, NY., Rosenberg JE; Genitourinary Oncology Service, Department of Medicine, MSK, New York, NY., Bochner BH; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY., Ostrovnaya I; Biostatistics Service, Department of Epidemiology & Biostatistics, MSK, New York, NY., Al-Ahmadie H; Genitourinary and Surgical Services, Department of Pathology, MSK, New York, NY., Solit DB; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, MSK, New York, NY.; Genitourinary Oncology Service, Department of Medicine, MSK, New York, NY.; Human Oncology and Pathogenesis Program, MSK, New York, NY., Iyer G; Genitourinary Oncology Service, Department of Medicine, MSK, New York, NY., Pietzak EJ; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY.
Jazyk:	angličtina
Zdroj:	JCO precision oncology [JCO Precis Oncol] 2024 Apr; Vol. 8, pp. e2300274.
DOI:	10.1200/PO.23.00274
Abstrakt:	Purpose: Patients with residual invasive bladder cancer after neoadjuvant chemotherapy (NAC) and radical cystectomy have a poor prognosis. Data on adjuvant therapy for these patients are conflicting. We sought to evaluate the natural history and genomic landscape of chemotherapy-resistant bladder cancer to inform patient management and clinical trials. Methods: Data were collected on patients with clinically localized muscle-invasive urothelial bladder cancer treated with NAC and cystectomy at our institution between May 15, 2001, and August 15, 2019, and completed four cycles of gemcitabine and cisplatin NAC, excluding those treated with adjuvant therapies. Survival was estimated using the Kaplan-Meier method, and multivariable Cox proportional hazards models were used to identify predictors of recurrence-free survival (RFS). Genomic alterations were identified in targeted exome sequencing (Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets) data from post-NAC specimens from a subset of patients. Results: Lymphovascular invasion (LVI) was the strongest predictor of RFS (hazard ratio, 2.15 [95% CI, 1.37 to 3.39]) on multivariable analysis. Patients with ypT2N0 disease without LVI had a significantly prolonged RFS compared with those with LVI (70% RFS at 5 years). Lymph node yield did not affect RFS. Among patients with sequencing data (n = 101), chemotherapy-resistant tumors had fewer alterations in DNA damage response genes compared with tumors from a publicly available chemotherapy-naïve cohort (15% v 29%; P = .021). Alterations in CDKN2A/B were associated with shorter RFS. PIK3CA alterations were associated with LVI. Potentially actionable alterations were identified in more than 75% of tumors. Conclusion: Although chemotherapy-resistant bladder cancer generally portends a poor prognosis, patients with organ-confined disease without LVI may be candidates for close observation without adjuvant therapy. The genomic landscape of chemotherapy-resistant tumors is similar to chemotherapy-naïve tumors. Therapeutic opportunities exist for targeted therapies as adjuvant treatment in chemotherapy-resistant disease.
Databáze:	MEDLINE
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