Pathologic outcomes at cytoreductive nephrectomy (CN) following immunotherapy (IO) for patients with advanced renal cell carcinoma (RCC).
Authors: Panian Justine , Saidian Ava , Hakimi Kevin , Ajmera Archana , Barata Pedro C. , Berg Stephanie A. , Chang Steven Lee , Choueiri Toni K. , Dzimitrowicz Hannah Elizabeth , Emamekhoo Hamid , Gross Evan , Kilari Deepak , Lam Elaine Tat , Lashgari Isabel , Psutka Sarah P. , Thapa Bicky , Weise Nicole , Zhang Tian , Derweesh Ithaar , McKay Rana R. 
Published: February 2022

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Background: IO, either as combination therapy in the frontline or monotherapy in the second line, has improved outcomes for patients with advanced RCC. With the movement away from upfront CN, limited data are available on the outcomes of patients who receive IO with delayed CN. In this study, we characterized the pathologic and survival outcomes for patients who received IO followed by CN. Methods: We conducted a multi-center, retrospective analysis of patients with advanced/metastatic RCC having received IO combination or monotherapy followed by CN. An IRB-approved and HIPAA-compliant registry was used to collect data from the electronic medical record. Our primary endpoint was the degree of pathologic downstaging comparing baseline clinical T stage to pathologic T stage following IO. Secondary endpoints included investigator assessed response using RECIST principals, progression-free survival (PFS), and overall survival (OS). Results: We identified53 patients with advanced RCC across 9 institutions who were eligible for the study. The median age was 63 years, 72% were white, and 60% were male. 81% of patients had clear cell histology, 11% had sarcomatoid differentiation, and 75% presented with de novo metastatic disease. Baseline IMDC risk is as follows: 4% favorable, 55% intermediate, and 26% poor risk with 15% unknown. 23% had bone metastases and 23% had liver metastases at baseline. Lines of therapy prior to CN was 1 line in 74% of patients, 2 lines in 25%, and 3 lines in 2%. For the line of IO therapy immediately preceding CN, 49% received nivolumab+ipilimumab, 30% received IO monotherapy, and 21% received combination IO/VEGF therapy. The median duration of therapy prior to surgery was 11.3 months (range 0.38-47.8). 28% of patients discontinued treatment after CN for observation. Best overall response prior to CN was stable disease in 25% of patients, partial response in 60%, and progressive disease in 4% with 11% unknown. Following receipt of IO-based treatment, 38% of patients exhibited downstaging from the baseline clinical T stage to the CN pathological T stage (Table). 11% of patients had no residual disease at CN. For pathologic outcomes, 85% of patients had negative margins, 75% had necrosis present, and the median tumor size at CN was 6.5 cm. The median PFS was 11.3 months and median OS was 25.7 months for the overall cohort. Conclusions: IO-based strategies demonstrate efficacy in the renal primary in patients with advanced RCC. T stage downstaging was demonstrated in 38% of patients with 11% having a complete pathologic response in the renal primary following IO administration. Biomarker studies on baseline and CN tissue will further elucidate molecular predictors of response and resistance to IO therapy.[Table: see text]