Eugene K Cha1, John P Sfakianos2, Ranjit Sukhu3, Alyssa M Yee1, Daniel D Sjoberg3, Bernard H Bochner1. 1. Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 2. Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 3. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Abstract
OBJECTIVES: To characterise the outcomes of neoadjuvant chemotherapy (NAC) pre-treated patients found to be lymph node (LN)-positive at the time of radical cystectomy and pelvic lymph node dissection (RC/PLND) for urothelial carcinoma of the bladder (UCB). PATIENTS AND METHODS: Of 1484 patients treated with RC/PLND for UCB from 2000 to 2010, we analysed 198 patients with clinically non-metastatic (cN0M0) muscle-invasive UCB who were found to be LN-positive at RC/PLND. As patients not receiving perioperative chemotherapy were significantly older and comorbid, we compared LN-positive patients previously treated with NAC (32 patients) to LN-positive patients treated with adjuvant chemotherapy (AC, 49 patients) using Cox proportional hazards models. A sensitivity analysis was designed to account for the additional time to RC in NAC patients. RESULTS: The 3-year recurrence-free survival estimate for LN-positive NAC patients was 26%, compared with 60% for LN-positive AC patients. LN-positive patients treated with NAC had significantly higher risks of disease recurrence and cancer-specific mortality in univariate analyses (hazard ratio [HR] 2.86, 95% confidence interval [CI] 1.58-5.19, P = 0.001 and HR 2.50, 95% CI 1.34-4.65, P = 0.004, respectively) and multivariable analyses adjusting for pathological stage and LN density (HR 3.11, 95% CI 1.59-6.07, P = 0.001 and HR 3.05, 95% CI 1.46-6.35, P = 0.003, respectively). Sensitivity analyses similarly demonstrated worse outcomes for NAC pre-treated LN-positive patients. CONCLUSION: LN-positive patients previously treated with NAC have a poor prognosis, significantly worse than LN-positive patients subsequently treated with AC, and should be considered for protocols using sandwich chemotherapy approaches or novel agents. These results should be considered in the interpretation of and stratification for clinical trials.
OBJECTIVES: To characterise the outcomes of neoadjuvant chemotherapy (NAC) pre-treated patients found to be lymph node (LN)-positive at the time of radical cystectomy and pelvic lymph node dissection (RC/PLND) for urothelial carcinoma of the bladder (UCB). PATIENTS AND METHODS: Of 1484 patients treated with RC/PLND for UCB from 2000 to 2010, we analysed 198 patients with clinically non-metastatic (cN0M0) muscle-invasive UCB who were found to be LN-positive at RC/PLND. As patients not receiving perioperative chemotherapy were significantly older and comorbid, we compared LN-positive patients previously treated with NAC (32 patients) to LN-positive patients treated with adjuvant chemotherapy (AC, 49 patients) using Cox proportional hazards models. A sensitivity analysis was designed to account for the additional time to RC in NACpatients. RESULTS: The 3-year recurrence-free survival estimate for LN-positive NACpatients was 26%, compared with 60% for LN-positive AC patients. LN-positive patients treated with NAC had significantly higher risks of disease recurrence and cancer-specific mortality in univariate analyses (hazard ratio [HR] 2.86, 95% confidence interval [CI] 1.58-5.19, P = 0.001 and HR 2.50, 95% CI 1.34-4.65, P = 0.004, respectively) and multivariable analyses adjusting for pathological stage and LN density (HR 3.11, 95% CI 1.59-6.07, P = 0.001 and HR 3.05, 95% CI 1.46-6.35, P = 0.003, respectively). Sensitivity analyses similarly demonstrated worse outcomes for NAC pre-treated LN-positive patients. CONCLUSION: LN-positive patients previously treated with NAC have a poor prognosis, significantly worse than LN-positive patients subsequently treated with AC, and should be considered for protocols using sandwich chemotherapy approaches or novel agents. These results should be considered in the interpretation of and stratification for clinical trials.
Authors: Marco Moschini; Stefania Zamboni; Agostino Mattei; Alberto Martini; Emanuele Zaffuto; Alberto Briganti; Andrea Gallina; Francesco Montorsi Journal: Transl Androl Urol Date: 2018-08