ASCO GU 2022: Pathologic Outcomes at Cytoreductive Nephrectomy Following Immunotherapy for Patients With Advanced RCC

(UroToday.com) The 2022 GU ASCO Annual meeting included a renal cell carcinoma (RCC) session highlighting work from Dr. Justine Panian and investigators presenting results assessing pathologic outcomes at cytoreductive nephrectomy following immunotherapy (IO) for patients with advanced RCC. 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 cytoreductive nephrectomy, limited data are available on the outcomes of patients who receive IO with delayed cytoreductive nephrectomy. In this study, Dr. Panian characterized the pathologic and survival outcomes for patients who received IO followed by cytoreductive nephrectomy.

 This was a multi-center, retrospective analysis of patients with advanced/metastatic RCC having received IO combination or monotherapy followed by cytoreductive nephrectomy. The primary endpoint for this study 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 principles, progression-free survival (PFS), and overall survival (OS).

 There were 52 patients identified with advanced RCC across 8 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 included 4% with favorable-risk disease, 55% intermediate-risk, and 26% poor risk with 15% unknown. Among these patients, 23% had bone metastases and 23% had liver metastases at baseline. Lines of therapy prior to cytoreductive nephrectomy included 74% of patients with 1 line, 2 lines in 25%, and 3 lines in 2% of patients. For the line of IO therapy immediately preceding cytoreductive nephrectomy, 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), and 28% of patients discontinued treatment after cytoreductive nephrectomy for observation. The best overall response prior to cytoreductive nephrectomy 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, 44% of patients exhibited downstaging from the baseline clinical T stage to the cytoreductive nephrectomy pathological T stage:

 

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There was 13% of patients that had no residual disease at cytoreductive nephrectomy. For pathologic outcomes, 85% of patients had negative margins, 75% had necrosis present, and the median tumor size at cytoreductive nephrectomy was 6.5 cm. In the overall cohort, the mean PFS was 53.7 months (95% CI 43.3-64.1):

 

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The mean OS was 75.5 months (95% CI 67.7-83.4) for the overall cohort:

 

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Dr. Panian concluded her presentation assessing pathologic outcomes at cytoreductive nephrectomy following immunotherapy for patients with advanced RCC with the following summary points:

  • IO-based strategies demonstrate efficacy in the renal primary in patients with advanced RCC
  • T stage downstaging was demonstrated in 44% of patients with 13% having a complete pathologic response in the renal primary following IO administration
  • Biomarker studies on baseline and cytoreductive nephrectomy tissue will further elucidate molecular predictors of response and resistance to IO therapy

 

Presented By: Justine Panian, MD Candidate, University of California San Diego, Moores Cancer Center, La Jolla, CA

Co-Authors: Ava Saidian, Kevin Hakimi, Archana Ajmera, Pedro C. Barata, Stephanie A. Berg, Steven Lee Chang, Toni Choueiri, Hannah Elizabeth Dzimitrowicz, Hamid Emamekhoo, Evan Gross, Deepak Kilari, Elaine Tat Lam, Isabel Lashgari, Sarah P. Psutka, Bicky Thapa, Nicole Weise, Tian Zhang, Ithaar Derweesh, Rana R. McKay

Affiliations: University of California San Diego, Moores Cancer Center, La Jolla, CA, UC-San Diego Health, La Jolla, CA, Tulane University Medical School, New Orleans, LA, Loyola University Medical Center, Maywood, IL, Division of Urological Surgery, Brigham and Women's Hospital, Boston, MA, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School, Duke Cancer Institute, Duke University, Durham, NC, University of Wisconsin School of Medicine and Public Health, Madison, WI, University of Washington School of Medicine, Seattle, WA, Department of Medicine, Froedtert Cancer Center, Medical College of Wisconsin, Milwaukee, WI, University of Colorado Cancer Center Anschutz Medical Campus, Aurora, CO, University of Washington Medical Center, Seattle, WA, Department of Medicine, Cleveland Clinic, Cleveland, OH, Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC, University of California San Diego, La Jolla, CA

 

Written By: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, Thursday Feb 17 – Saturday Feb 19, 2022

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