ORIGINAL ARTICLE   Free access

Minerva Urology and Nephrology 2023 June;75(3):319-28

DOI: 10.23736/S2724-6051.23.05151-0

Copyright © 2023 EDIZIONI MINERVA MEDICA

language: English

Cancer-specific mortality free survival rates in non-metastatic non-clear cell renal carcinoma patients at intermediate/high risk of recurrence

Mattia L. PICCINELLI ^{1, 2, 3} ✉, Andrea PANUNZIO ^{1, 4}, Stefano TAPPERO ^{1, 5, 6}, Cristina CANO GARCIA ^{1, 7}, Francesco BARLETTA ^{1, 8}, Reha-Baris INCESU ^{1, 9}, Zhe TIAN ¹, Stefano LUZZAGO ^{2, 10}, Francesco A. MISTRETTA ^{2, 10}, Matteo FERRO ², Fred SAAD ¹, Shahrokh F. SHARIAT ^{11, 12, 13, 14}, Derya TILKI ^{9, 15, 16}, Alberto BRIGANTI ⁸, Felix K. CHUN ⁷, Carlo TERRONE ^{5, 6}, Alessandro ANTONELLI ⁴, Ottavio DE COBELLI ^{2, 10}, Gennaro MUSI ^{2, 10}, Pierre I. KARAKIEWICZ ¹

¹ Division of Urology, Unit of Cancer Prognostics and Health Outcomes, University of Montréal Health Center, Montréal, Canada; ² Department of Urology, IEO IRCCS European Institute of Oncology, Milan, Italy; ³ University of Milan, Milan, Italy; ⁴ Department of Urology, Azienda Ospedaliera Universitaria Integrata di Verona, University of Verona, Verona, Italy; ⁵ Department of Urology, IRCCS San Martino Policlinic Hospital, Genoa, Italy; ⁶ Department of Surgical and Diagnostic Integrated Sciences (DISC), University of Genoa, Genoa, Italy; ⁷ Department of Urology, University Hospital of Frankfurt, Goethe University Frankfurt am Main, Frankfurt am Main, Germany; ⁸ Division of Experimental Oncology, Unit of Urology, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy; ⁹ Martini-Klinik Prostate Cancer Center, University Hospital of Hamburg-Eppendorf, Hamburg, Germany; ¹⁰ Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy; ¹¹ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; ¹² Department of Urology, Weill Cornell Medical College, New York, NY, USA; ¹³ Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA; ¹⁴ Hourani Center of Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan; ¹⁵ Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany; ¹⁶ Department of Urology, Koc University Hospital, Istanbul, Türkiye

BACKGROUND: To date, five trials testing the effect of adjuvant systemic therapy in surgically treated non-metastatic renal cell carcinoma included patients with non-clear cell histology. We tested the effect of papillary vs. chromophobe histological subtype, stage, and grade on 10-year cancer-specific survival, in patients eligible for ≥1 such trial.
METHODS: We identified patients meeting ASSURE, SORCE, EVEREST, PROSPER, or RAMPART trial inclusion criteria in the SEER (2000-2018) database. Kaplan-Meier analyses estimated 10-year survival rates and multivariable Cox regression models tested for the independent predictor status of histological subtype, stage, and grade.
RESULTS: We identified 5465 (68%) papillary and 2562 (32%) chromophobe renal cell carcinoma patients. Cancer-specific survival rates at 10 years were 77% in papillary vs. 90% in chromophobe. In multivariable Cox regression models applied to papillary patients, cancer-specific mortality independent predictor status was reached for T3G3-4 (HR 2.9), T4Gany (HR 3.4), TanyN1G1-2 (HR 3.1), and TanyN1G3-4 (HR 8.0, P<0.001), relative to T1/2Gany. In multivariable Cox regression models applied to chromophobe patients, mortality independent predictor status was reached for T3G3-4 (HR 3.6), T4Gany (HR 14.0), TanyN1G1-2 (HR 5.7), and TanyN1G3-4 (HR 15.0, P<0.001), relative to T1/2Gany.
CONCLUSIONS: In surgically treated non-metastatic intermediate/high-risk renal cell carcinoma patients, papillary histologic subtype exhibited worse cancer-specific survival than chromophobe histologic subtype. Although stage and grade represented independent predictors in both histological subtype groups, the magnitude of their effect was invariably worse in chromophobe than in papillary patients. In consequence, papillary and chromophobe patients should be considered separate entities instead of being combined under the non-clear cell designation.

KEY WORDS: Carcinoma, renal cell; Survival; Randomized controlled trials as topic; Chromophobe