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)

• Published in: Annals of oncology Vol. 29; no. 2; pp. 361 - 369
• Main Authors: Bamias, A., Tzannis, K., Harshman, L.C., Crabb, S.J., Wong, Y.-N., Kumar Pal, S., De Giorgi, U., Ladoire, S., Agarwal, N., Yu, E.Y., Niegisch, G., Necchi, A., Sternberg, C.N., Srinivas, S., Alva, A., Vaishampayan, U., Cerbone, L., Liontos, M., Rosenberg, J., Powles, T., Bellmunt, J., Galsky, M.D.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2018; Oxford University Press; Elsevier
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer; chemotherapy; Cisplatin - administration & dosage; cisplatin eligibility; Humans; Life Sciences; Retrospective Studies; Treatment Outcome; Urogenital tumor; Urologic Neoplasms - drug therapy; Urologic Neoplasms - mortality; urothelial cancer; chemotherapy; urothelial cancer; cisplatin eligibility
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdx692

Cisplatin-based combination chemotherapy is the standard treatment of 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. This 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 performance status ≤1, creatinine clearance ≥60 ml/min, no hearing loss, no neuropathy and no heart failure. Cox regression multivariate analyses were used to establish independent associations of cisplatin versus noncisplatin-based chemotherapy on OS. About 1794 patients treated between 2000 and 2013 at 29 centers were analyzed. Median follow-up was 29.1 months. About 1333 patients (74%) received first-line chemotherapy: the use of first-line chemotherapy was associated with longer OS: [hazard ratio (HR): 1.91, 95% confidence interval (CI): 1.67–2.20]. Type of first-line chemotherapy received was: cisplatin-based 669 (50%), carboplatin-based 399 (30%) and 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 comorbidities 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. About 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. The 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.