Incidence, Patterns, and Outcomes with Adjuvant Chemotherapy for Residual Disease After Neoadjuvant Chemotherapy in Muscle-invasive Urinary Tract Cancers.

Patients with residual muscle-invasive urinary tract cancer after neoadjuvant chemotherapy (NAC) have a high risk of recurrence.

To retrospectively evaluate whether additional adjuvant chemotherapy (AC) improves outcomes compared with surveillance in patients with significant residual disease despite NAC.

We identified 474 patients who received NAC from the Retrospective International Study of Cancers of the Urothelium database, of whom 129 had adverse residual disease (≥ypT3 and/or ypN+).

Time to relapse (TTR) was the primary endpoint assessed starting from 2mo after surgery to minimize immortal time bias. Secondary endpoints included overall survival (OS), incidence of AC use, and chemotherapy patterns. Kaplan-Meier and Cox regression models estimated TTR, OS, and associations with AC, adjusting for the type of NAC, age, and pathological stage in multivariable analyses.

A total of 106 patients underwent surveillance, while 23 received AC. Gemcitabine-cisplatin was the most frequent regimen employed in both settings (30.4%), and the majority (82.6%) of the patients switched to a different regimen. Median follow-up was 30mo. Over 50% of patients developed a recurrence. Median TTR was 16mo (range: <1-108mo). Longer median TTR was observed with AC compared with surveillance (18 vs 10mo, p=0.06). Risk of relapse significantly decreased with AC when adjusted in multivariable analyses (p=0.01). The subgroup analyses of ypT4b/ypN+ patients (AC: 19; surveillance: 50) who received AC had significantly greater median TTR (20 vs 9mo; hazard ratio 0.43; 95% confidence interval: 0.21-0.89). No difference in OS was found. Limitations include the retrospective design.

The utilization of AC after NAC in patients with high-risk residual disease is not frequent in clinical practice but might reduce the risk of recurrence. Further investigation is needed in this high-risk population to identify optimal therapy and to improve clinical outcomes such as the ongoing adjuvant immunotherapy trials.

We found that administering additional chemotherapy in patients who had significant residual disease despite preoperative chemotherapy is not frequent in clinical practice. While it might reduce the risk of recurrence, it did not clearly increase overall survival. We encourage participation in the ongoing immunotherapy trials to see whether we can improve outcomes using a different type of therapy that stimulates the immune system.

European urology oncology. 2019 Jan 30 [Epub ahead of print]

Nieves Martinez Chanza, Lillian Werner, Elizabeth Plimack, Evan Y Yu, Ajjai S Alva, Simon J Crabb, Thomas Powles, Jonathan E Rosenberg, Jack Baniel, Ulka N Vaishampayan, Dominik R Berthold, Sylvain Ladoire, Syed A Hussain, Matthew I Milowsky, Neeraj Agarwal, Andrea Necchi, Sumanta K Pal, Cora N Sternberg, Joaquim Bellmunt, Matthew D Galsky, Lauren C Harshman, RISC Investigators

Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Fox Chase Cancer Center, Philadelphia, PA, USA., Fred Hutchinson Cancer Research Center, Seattle, WA, USA., University of Michigan, Ann Arbor, MI, USA., University of Southampton, Southampton, UK., Barts Cancer Institute, London, UK., Memorial Sloan Kettering Cancer Center, New York, NY, USA., Rabin Medical Center, Petah Tivka, Israel., Karmanos Cancer Institute, Detroit, MI, USA., Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland., Georges François Leclerc Cancer Center, Dijon, France., Clatterbridge Cancer Centre, Liverpool, UK., UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA., Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT, USA., Istituto Nazionale Tumori of Milan, Milano, MI, Italy., City of Hope, Duarte, CA, USA., San Camillo-Forlanini Hospital, Rome, Italy., The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Electronic address: .