Pathological Outcomes of Patients With Advanced Renal Cell Carcinoma Who Receive Nephrectomy Following Immunotherapy

Justine Panian; Ava Saidian; Kevin Hakimi; Archana Ajmera; William J Anderson; Pedro Barata; Stephanie Berg; Sabina Signoretti; Steven Lee Chang; Vincent D'Andrea; Daniel George; Hannah Dzimitrowicz; Talal El Zarif; Hamid Emamekhoo; Evan Gross; Deepak Kilari; Elaine Lam; Isabel Lashgari; Sarah Psutka; Grant P Rauterkus; Ahmed Shabaik; Bicky Thapa; Luke Wang; Nicole Weise; Kendrick Yim; Tian Zhang; Ithaar Derweesh; Rana R McKay

doi:10.1093/oncolo/oyad166

Pathological Outcomes of Patients With Advanced Renal Cell Carcinoma Who Receive Nephrectomy Following Immunotherapy

Oncologist. 2023 Jun 27:oyad166. doi: 10.1093/oncolo/oyad166. Online ahead of print.

Authors

Justine Panian¹, Ava Saidian², Kevin Hakimi², Archana Ajmera³, William J Anderson⁴, Pedro Barata⁵, Stephanie Berg⁶, Sabina Signoretti⁴, Steven Lee Chang⁷, Vincent D'Andrea⁷, Daniel George⁸, Hannah Dzimitrowicz⁸, Talal El Zarif⁹, Hamid Emamekhoo¹⁰, Evan Gross¹¹, Deepak Kilari¹², Elaine Lam¹³, Isabel Lashgari¹⁴, Sarah Psutka¹¹, Grant P Rauterkus⁵, Ahmed Shabaik¹⁵, Bicky Thapa¹², Luke Wang², Nicole Weise¹, Kendrick Yim⁷, Tian Zhang¹⁶, Ithaar Derweesh², Rana R McKay¹⁷

Affiliations

¹ University of California San Diego, Department of Medicine, Division of Hematology-Oncology La Jolla, CA, USA.
² University of California San Diego, Department of Urology, La Jolla, CA, USA.
³ University of California San Diego, Department of Medicine, Division of Hematology-Oncology, La Jolla, CA, USA.
⁴ Brigham and Women's Hospital, Department of Pathology, Boston, MA, USA.
⁵ Tulane University, Deming Department of Medicine, New Orleans, LA, USA.
⁶ Loyola University Chicago, Department of Cancer Biology and Internal Medicine, Maywood, IL, USA.
⁷ Brigham and Women's Hospital, Division of Urology, Boston, MA, USA.
⁸ Duke Cancer Institute, Department of Medicine, Durham, NC, USA.
⁹ Dana-Farber Cancer Institute, Department of Medical Oncology, Boston, MA, USA.
¹⁰ University of Wisconsin, Department of Medicine, Madison, WI, USA.
¹¹ The University of Washington, Department of Urology, Seattle, WA, USA.
¹² Medical College of Wisconsin, Department of Internal Medicine, Milwaukee, WI, USA.
¹³ University of Colorado Cancer Center, Division of Medical Oncology, Aurora, CO, USA.
¹⁴ San Diego State University, Department of Cell and Molecular Biology, San Diego, CA, USA.
¹⁵ University of California San Diego, Department of Pathology, La Jolla, CA, USA.
¹⁶ UT Southwestern, Department of Internal Medicine, Dallas, TX, USA.
¹⁷ University of California San Diego, Department of Medicine, Department of Urology, La Jolla, CA, USA.

PMID: 37368355
DOI: 10.1093/oncolo/oyad166

Abstract

Background: Even though cytoreductive nephrectomy (CN) was once the standard of care for patients with advanced renal cell carcinoma (RCC), its role in treatment has not been well analyzed or defined in the era of immunotherapy (IO).

Materials and methods: This study analyzed pathological outcomes in patients with advanced or metastatic RCC who received IO prior to CN. This was a multi-institutional, retrospective study of patients with advanced or metastatic RCC. Patients were required to receive IO monotherapy or combination therapy prior to radical or partial CN. The primary endpoint assessed surgical pathologic outcomes, including American Joint Committee on Cancer (AJCC) staging and frequency of downstaging, at the time of surgery. Pathologic outcomes were correlated to clinical variables using a Wald-chi squared test from Cox regression in a multi-variable analysis. Secondary outcomes included objective response rate (ORR) defined by response evaluation criteria in solid tumors (RECIST) version 1.1 and progression-free survival (PFS), which were estimated using the Kaplan-Meier method with reported 95% CIs.

Results: Fifty-two patients from 9 sites were included. Most patients were male (65%), 81% had clear cell histology, 11% had sarcomatoid differentiation. Overall, 44% of patients experienced pathologic downstaging, and 13% had a complete pathologic response. The ORR immediately prior to nephrectomy was stable disease in 29% of patients, partial response in 63%, progressive disease in 4%, and 4% unknown. Median follow-up for the entire cohort was 25.3 months and median PFS was 3.5 years (95% CI, 2.1-4.9).

Conclusions: IO-based interventions prior to CN in patients with advanced or metastatic RCC demonstrates efficacy, with a small fraction of patients showing a complete response. Additional prospective studies are warranted to investigate the role of CN in the modern IO-era.

Keywords: immunotherapy; metastatic; nephrectomy; pathologic; renal cell carcinoma.