ESMO 2017: Adjuvant chemotherapy after radical nephroureterectomy does not improve survival in patients with upper tract urothelial carcinoma: A joint study of the EAU-Young Academic Urologists and the Upper Tract Urothelial Carcinoma Collaboration

Madrid, Spain (UroToday.com) Dr. Andrea Necchi and international colleagues presented results assessing adjuvant chemotherapy after radical nephroureterectomy for upper tract urothelial carcinoma (UTUC) at today’s poster session at ESMO 2017 in Madrid, Spain. In patients with UTUC the benefit of adjuvant chemotherapy after radical nephroureterectomy is debated secondary to a lack of prospective randomized trials. The objective of this study was to assess the benefit of adjuvant chemotherapy vs observation in an international study.

For this study, data from 15 centers was collected, totaling 1,544 patients treated between 2000 and 2015. Criteria for patient selection included: (i) UTUC diagnosis, and (ii) pT2-4N0/x and/or pN+ stage undergoing radical nephroureterectomy. The standardized differences (SD) approach was used to compare subgroup characteristics. Overall survival (OS) was the primary endpoint. The adopted propensity scores techniques included 1:1 propensity score matching and inverse probability of treatment weighting (IPTW). Additionally, the IPTW analysis was performed with the inclusion of the covariates, i.e. with doubly robust estimation (DREP). Finally, six-month landmark analysis was also performed.

A total of 312 patients (20.2%) received adjuvant chemotherapy and 1,232 underwent observation. Despite differences between the two groups, SD was generally <10% after matching. In the DREP-adjusted comparison, adjuvant chemotherapy was significantly associated with shorter OS (HR 1.25, 95%CI 1.02-1.54), while no difference was observed in the matched analysis (HR 1.14, 95%CI 0.91-1.43). These findings were confirmed in subgroup analyses (pT2N0/x; pT3-4N0/x; pTanyN+). The six-month landmark analysis demonstrated little impact of early events on the treatment effect on OS (HR of the propensity score-matched analysis 1.28, 95%CI 1.00-1.64). Relapse-free survival outcomes were overlapping to OS in the matched analyses (adjuvant chemotherapy, HR 1.59 95%CI 1.25-2.02). A potential limitation of this study acknowledged by the authors is the retrospective nature and the associated inherent selection biases.

In conclusion, adjuvant chemotherapy does not improve OS compared to observation in pT2-4 and/or pN+ UTUC. These findings contribute to the uncertainties regarding adjuvant chemotherapy in UTUC and further support the need for dedicated prospective trials in UTUC, more potent new therapies, standardized lymphadenectomy templates, and enhanced patient selection criteria.

Speaker: Andrea Necchi, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

Co-Authors: S. Lo Vullo (Milan, Italy) L. Mariani (Milan, Italy) M. Moschini (Luzern, Switzerland) K. Hendricksen (Amsterdam, Netherlands) M. Rink (Eppendorf, Germany) R. Sosnowski (Otwock, Poland) J. Dobruch (Warsaw, Poland) J. D. Raman (Hershey, United States of America) C. G. Wood (Houston, United States of America) V. Margulis (Dallas, United States of America) M. Rouprêt (Paris, France) A. Briganti (Milano, Italy) F. Montorsi (Milan, Italy) E. Xylinas (Paris, France) S. F. Shariat (Vienna, Austria)

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain

References:

Heery CR, O’Sullivan-Coyne G, Madan RA, et al. Avelumab for metastatic or locally advanced previously treated solid tumours (JAVELIN Solid Tumor): A phase 1a, multicohort, dose-escalation trial. Lancet Oncol 2017;18(5):587-598.
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