Natural History and Genomic Landscape of Chemotherapy-Resistant Muscle-Invasive Bladder Cancer.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
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Lenis Andrew T, Whiting Karissa, Ravichandran Vignesh, Tallman Jacob E, Alam Syed M, Chu Carissa E, Jesus Escano Manual De, Bochner Emily, Katims Andrew, Reisz Peter A, Truong Hong, Clinton Timothy N, Telis Leon, Dason Shawn, McPherson Victor, Teo Min Yuen, Funt Samuel, Aggen David, Goh Alvin C, Donahue Timothy F, Cha Eugene K, Donat S Machele, Herr Harry W, Dalbagni Guido, Schultz Nikolaus, Berger Michael F, Bajorin Dean F, Rosenberg Jonathan E, Bochner Bernard H, Ostrovnaya Irina, Al-Ahmadie Hikmat, Solit David B, Iyer Gopa, Pietzak Eugene J
Аннотация
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.