Contemporary use and survival after perioperative systemic chemotherapy in patients with locally advanced non-metastatic urothelial carcinoma of the bladder treated with radical cystectomy.


Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Quebec, Canada; Division of Oncology, Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. Electronic address: [Email]


BACKGROUND : Locally advanced muscle-invasive bladder cancer (MIBC) patients who are candidates for radical cystectomy (RC) should receive perioperative chemotherapy (CHT). However, the adherence to CHT guidelines is low. Thus, we tested contemporary CHT use rates and associated cancer-specific mortality (CSM) and overall mortality (OM) rates.
METHODS : Within the SEER database (2004-2015), we identified pT3N0/+ MIBC patients, who underwent RC, with or without perioperative CHT. Estimated annual percentage changes (EAPCs) analyses were used. After inverse probability of treatment weighting (IPTW), Kaplan-Meier (KM) analyses and Cox regression models (CRMs) tested the association of CHT on survival in the overall population (n = 3817), as well as after stratification according to stage, gender and age. Landmark analyses tested for immortal time bias.
RESULTS : Overall, 44.3% of patients received CHT. Between 2004 and 2015, CHT administration rates increased from 32.1% to 55.6% (EAPC: +6.0%; p < 0.001). In CRMs, CHT was associated with lower CSM (HR 0.73, CI 0.65-0.81) and OM (HR 0.69, CI 0.62-0.76). In sensitivity analyses, CHT was also associated with lower CSM and OM in N0 patients (CSM: HR 0.76, 95% CI 0.65-0.88; OM: HR 0.69, 95% CI 0.60-0.79) and in N+ patients (CSM: HR 0.69, 95% CI 0.59-0.80; OM: HR 0.67, 95% CI 0.58-0.77), as well as according to gender and age. Landmark analyses confirmed the above results.
CONCLUSIONS : Perioperative CHT was associated with better survival and its rate of use increased in locally-advanced MIBC RC patients. The latter confirm one large observational study and several small prospective studies.


Cancer-specific mortality,Chemotherapy,Locally advanced bladder cancer,Radical cystectomy,SEER program,

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