Impact of contemporary patterns of chemotherapy utilization on survival in patients with advanced cancer of the urinary tract: A Retrospective International Study of Invasive/advanced cancer of the urothelium (RISC)

BackgroundCisplatin-based combination chemotherapy is the standard treatment for advanced urinary tract cancer (aUTC) but 50% of patients are ineligible for cisplatin according to recently published criteria. We used a multinational database to study patterns of chemotherapy utilization in patients with aUTC and determine their impact on survival.Patients and MethodsThis was a retrospective study of patients with: UTC (bladder, renal pelvis, ureter or urethra); advanced disease (stages T4b and/or N+ and/or M+); urothelial, squamous or adenocarcinoma histology. Primary objective was overall survival (OS). Eligibility-for-cisplatin was defined by: Eastern Cooperative Oncology group (ECOG) performance status (PS)≤1, creatinine clearance (CrCl)≥60 ml/min, no hearing loss, no neuropathy, no heart failure. Cox regression multivariate analyses were used to establish independent associations of cisplatin vs. non-cisplatin-based chemotherapy on OS.Results1794 patients treated between 2000 and 2013 at 29 centers were analyzed. Median follow-up was 29.1 months. 1333 patients (74%) received 1st-line chemotherapy: Use of 1st-line chemotherapy was associated with longer OS: (Hazard ratio [HR]: 1.91, 95% confidence interval [CI]: 1.67-2.20). Type of 1st-line chemotherapy received was: cisplatin-based 669 (50%), carboplatin-based 399 (30%), other 265 (20%). Cisplatin use was an independent favorable prognostic factor (HR: 1.54, 95% CI: 1.35-1.77). This benefit was independent of baseline characteristics or co-morbidities but was associated with eligibility-for-cisplatin: eligible patients treated with cisplatin lived longer than those who were not (HR: 1.74, 95% CI: 1.36-2.21), while such benefit was not observed among ineligible patients. 26% of patients who did not receive cisplatin were eligible for this agent. Median OS of ineligible patients was poor irrespective of the chemotherapy used.ConclusionsThe importance of applying published criteria of eligibility-for-cisplatin was confirmed in a multinational, real-world setting in aUTC. The reasons for deviations from these criteria set targets to improve adherence. Effective therapies for cisplatin-ineligible patients are needed.

Annals of oncology : official journal of the European Society for Medical Oncology. 2017 Oct 25 [Epub ahead of print]

A Bamias, K Tzannis, L C Harshman, S J Crabb, Y-N Wong, S Kumar Pal, U De Giorgi, S Ladoire, N Agarwal, E Y Yu, G Niegisch, A Necchi, C N Sternberg, S Srinivas, A Alva, U Vaishampayan, L Cerbone, M Liontos, J Rosenberg, T Powles, J Belmunt, M D Galsky, RISC Investigators

Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., Dana-Farber Cancer Institute, Boston, MA, USA., University of Southampton, Southampton, United Kingdom., Fox Chase Cancer Center, Philadelphia, PA, USA., City of Hope Comprehensive Cancer Center, Duarte, CA, USA., IRCCS Istituto Scientifico Romagnolo per lo studio e la Cura dei Tumori, Meldola, Italy., Center Georges-François Leclerc, Dijon, France., University of Utah, Salt Lake City, UT, USA., University of Washington, Seattle, WA, USA., Department of Urology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany., Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy., San Camillo Forlanini Hospital, Rome, Italy., Stanford University School of Medicine, Stanford, CA, USA., University of Michigan, Ann Arbor, MI, USA., Karmanos Cancer Institute, Detroit, MI, USA., Memorial Sloan-Kettering Cancer Center, New York, NY, USA., Barts Health and the Royal Free NHS Trust, Queen Mary University of London, London, United Kingdom., Mount Sinai School of Medicine, Tisch Cancer Institute, New York, NY, USA.