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)

Abstract

Background: 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.

Patients and methods: 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.

Results: 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.

Conclusions: 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.

Supplementary Appendix

Supplementary Tables and Figure S1 Legend

Figure 1

Study flow chart.

Supplementary Figure S1

Figure 2

Kaplan–Meier curves of overall survival (OS) according to the type of first-line chemotherapy (A); Forest plot of subgroup analysis according to the type of first-line chemotherapy (B); Kaplan–Meier curves of OS according to: the type of first-line chemotherapy stratified by eligibility-for-cisplatin (C). Maximum analysis time to be graphed was selected at 6 years. Patients alive at 6 years (regardless of subsequent death) were censored at that time. Blue dots in forest plot denote hazard ratios for the treatment type and horizontal bars 95% confidence interval. Interaction refers to potential interactions of the effects of treatment type (cisplatin versus carboplatin + other) and each of the covariates listed on the left-hand side of the figure. P-value of interaction refers to the P-value of the interaction term from a Cox model, which includes treatment type and the respective covariate. CCI, Charlson Comorbidity Index; COPD, chronic obstructive airway disease; PS, performance status; Hgb, hemoglobin; WBC, while blood cells.