Pathologic outcomes at cytoreductive nephrectomy (CN) following immunotherapy (IO) for patients with advanced renal cell carcinoma (RCC).

Authors

Justine Panian

Justine Panian

University of California San Diego, Moores Cancer Center, La Jolla, CA

Justine Panian , Ava Saidian , Kevin Hakimi , Archana Ajmera , Pedro C. Barata , Stephanie A. Berg , Steven Lee Chang , Toni K. 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

Organizations

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, Boston, MA, 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

Research Funding

No funding received

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.


Baseline T Stage
Pathologic T Stage
T0
0 (0%)
6 (11%)
T1
6 (11%)
9 (17%)
T2
14 (26%)
5 (9%)
T3
22 (42%)
30 (57%)
T4
10 (19%)
3 (6%)

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Abstract Details

Meeting

2022 ASCO Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session C: Renal Cell Cancer; Adrenal, Penile, Urethral, and Testicular Cancers

Track

Renal Cell Cancer,Adrenal Cancer,Penile Cancer,Testicular Cancer,Urethral Cancer

Sub Track

Therapeutics

Citation

J Clin Oncol 40, 2022 (suppl 6; abstr 334)

DOI

10.1200/JCO.2022.40.6_suppl.334

Abstract #

334

Poster Bd #

F7

Abstract Disclosures

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