Efficacy of Surgery in the Primary Tumor Site for Metastatic Urothelial Cancer: Analysis of an International, Multicenter, Multidisciplinary Database

Abstract

Background: The effect of local treatment on survival in advanced-stage patients has gained interest in several malignancies; however, limited data exist regarding urothelial carcinoma (UC). Objective: To test the impact of surgery of the primary tumor site on cancer-specific mortality (CSM) and overall mortality (OM) in patients affected by metastatic UC. Design, setting, and participants: Individual patient-level data from a multicenter collaboration, including metastatic UC patients treated with first-line cisplatin- or carboplatin-based chemotherapy administered between January 2006 and January 2011 from hospitals in the USA, Europe, Israel, and Canada. Outcome measurements and statistical analysis: Univariable and multivariable Cox regression analyses were used to assess the effect of surgery on CSM and OM in patients affected by metastatic UC using 3-mo landmark analyses. Subgroup analyses were performed on the basis of the number of metastasis sites involved and including only patients treated with surgery before the start of chemotherapy. Results and limitations: Of the 326 patients included in the study, 47 (14%) were treated with surgery of the primary tumor site. Median (interquartile range) follow-up was 43 (33–45) mo. Of the patients treated with surgery, 28 (60%) were affected by a primary bladder cancer and 19 (40%) by a primary upper urinary tract tumor. On multivariable analyses, surgery was associated with a protective effect on CSM (hazard ratio [HR]: 0.59, confidence interval [CI]: 0.35–0.98, p = 0.04) and OM (HR: 0.45, CI: 0.37–0.99, p = 0.04) compared with patients treated with chemotherapy only. Similar results were found considering patients only surgically treated before the start of chemotherapy. After stratifying according to the number of metastatic sites, surgery has an effect on survival in patients with only one metastatic site, while no survival benefit was observed in patients with two or more metastatic sites. The study is limited by its retrospective nature. Conclusions: We found that surgery of the primary tumor site is associated with improved survival in patients with metastatic UC who received standard chemotherapy. This effect disappears in patients affected by two or more metastatic sites. Our results need to be validated in a high-quality prospective trial. Patient summary: In our multicenter, retrospective series, surgery in metastatic urothelial cancer patients improve survival compared with patients treated with chemotherapy only. This effect was evident in patients with limited disease extent, identified as one metastatic site. Patients affected by metastatic urothelial carcinoma treated with surgery in the primary tumor site in addition to standard chemotherapy recorded improved survival compared with patients treated with chemotherapy only. This effect is preponderant in patients with a single metastatic site. © 2019 European Association of Urolog