Outcomes of Consolidative Nephrectomy following Primary Immunotherapy in Advanced Renal Cell Carcinoma: A Multicenter Analysis

Kevin Hakimi; Ava Saidian; Justine Panian; Pedro Barata; Stephanie Berg; Steven L Chang; Renee M Saliby; Hannah Dzimitrowicz; Hamid Emamekhoo; Evan Gross; Deepak Kilari; Elaine Lam; Mimi Nguyen; Margaret Meagher; Luke Wang; Grant P Rauterkus; Vincent D'Andrea; Kendrick Yim; Sarah Psutka; Bicky Thapa; Nicole Weise; Tian Zhang; Rana R McKay; Ithaar H Derweesh

doi:10.1016/j.clgc.2023.07.007

Outcomes of Consolidative Nephrectomy following Primary Immunotherapy in Advanced Renal Cell Carcinoma: A Multicenter Analysis

Clin Genitourin Cancer. 2023 Dec;21(6):694-702. doi: 10.1016/j.clgc.2023.07.007. Epub 2023 Jul 19.

Authors

Kevin Hakimi¹, Ava Saidian¹, Justine Panian², Pedro Barata³, Stephanie Berg⁴, Steven L Chang⁵, Renee M Saliby⁶, Hannah Dzimitrowicz⁷, Hamid Emamekhoo⁸, Evan Gross⁹, Deepak Kilari¹⁰, Elaine Lam¹¹, Mimi Nguyen¹, Margaret Meagher¹, Luke Wang¹, Grant P Rauterkus³, Vincent D'Andrea⁶, Kendrick Yim⁶, Sarah Psutka⁹, Bicky Thapa¹⁰, Nicole Weise², Tian Zhang¹², Rana R McKay², Ithaar H Derweesh¹³

Affiliations

¹ Department of Urology, UC San Diego School of Medicine, San Diego, CA.
² Deparment of Internal Medicine, Division of Hematology and Medical Oncology, UC San Diego School of Medicine, San Diego, CA.
³ Department of Hematology and Medical Oncology, Tulane University School of Medicine, New Orleans, LA.
⁴ Department of Hematology and Medical Oncology, Loyola University Medical Center, Maywood, IL.
⁵ Division of Urology, Brigham and Women's Hospital, Boston, MA.
⁶ Lark Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA.
⁷ Department of Medicine, Duke University School of Medicine, Durham, NC.
⁸ Department of Hematology and Medical Oncology, University of Wisconsin School of Medicine, Madison, WI.
⁹ Department of Hematology and Medical Oncology, University of Washington School of Medicine, Seattle, WA.
¹⁰ Division of Hematology and Medical Oncology, Medical College of Wisconsin, Milwaukee, WI.
¹¹ Department of Hematology and Medical Oncology, University of Colorado School of Medicine, Aurora, CO.
¹² Department of Hematology and Medical Oncology, University of Texas Southwestern Medical Center, Dallas, TX.
¹³ Department of Urology, UC San Diego School of Medicine, San Diego, CA. Electronic address: iderweesh@gmail.com.

PMID: 37558529
DOI: 10.1016/j.clgc.2023.07.007

Abstract

Background: To evaluate effect and outcomes of combination primary immunotherapy (IO) and nephrectomy for advanced renal cell carcinoma (RCC).

Methods: We conducted a multicenter, retrospective analysis of patients with advanced/metastatic RCC who received IO followed by nephrectomy. Primary outcome was Bifecta (negative surgical margins and no 30-day surgical complications). Secondary outcomes included progression-free survival (PFS) following surgery, reduction in tumor/thrombus size, RENAL score, and clinical/pathologic downstaging. Cox regression multivariable analysis was conducted for predictors of Bifecta and PFS. Kaplan-Meier analysis assessed PFS, comparing Bifecta and non-Bifecta groups.

Results: A total of 56 patients were analyzed (median age 63 years; median follow-up 22.5 months). A total of 40 (71.4%) patients were intermediate IMDC risk. Patients were treated with immunotherapy for median duration of 8.1 months. Immunotherapy resulted in reductions in tumor size (P < .001), thrombus size (P = .02), and RENAL score (P < .001); 38 (67.9%) patients were clinically downstaged on imaging (P < .001) and 25 (44.6%) patients were pathologically downstaged following surgery (P < .001). Bifecta was achieved in 38 (67.9%) patients. Predictors for bifecta achievement included decreasing tumor size (HR 1.08, P = .043) and pathological downstaging (HR 2.13, P = .047). Bifecta (HR 5.65, P = .009), pathologic downstaging (HR 5.15, P = .02), and increasing reduction in tumor size (HR 1.2, P = .007) were associated with improved PFS. Bifecta patients demonstrated improved 2-year PFS (84% vs. 71%, P = .019).

Conclusions: Primary immunotherapy reduced tumor/thrombus size and complexity. Pathologically downstaged patients were more likely to achieve bifecta, and these patients displayed improved 2-year PFS. Our study supports further inquiry in the use of CRN following primary immunotherapy for advanced renal cancer.

Keywords: Bifecta; Complications; Consolidative nephrectomy; Immunotherapy; Pathological downstaging; Renal cell carcinoma; Tumor thrombus.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Renal Cell* / surgery
Humans
Immunotherapy
Kidney Neoplasms* / surgery
Middle Aged
Nephrectomy / methods
Retrospective Studies
Thrombosis* / surgery