Cytoreductive Nephrectomy and Metastatic Renal Cell Carcinoma: State of the Art and Future Perspectives

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Abstract

In the past decades, several treatments have been proposed for the management of metastatic renal cell carcinoma (mRCC). Among these, cytoreductive nephrectomy (CN) represents a controversial and open issue in the era of targeted therapy and novel immunotherapy with immune checkpoint inhibitors. Two important studies, CARMENA and SURTIME, analyzed therapy with sunitinib with or without CN, and immediate CN followed by sunitinib versus a deferred CN after three cycles of sunitinib, respectively. CARMENA showed the non-inferiority of sunitinib alone versus sunitinib plus CN, whereas SURTIME showed no difference in progression-free survival (PFS), but a better median OS among patients with deferred CN. Therefore, more prospective clinical trials and appropriate patient identification are necessary to support CN in this new scenario. This review provides a snapshot of the current evidence for CN in mRCC, discusses the management strategies, and offers perspectives on the direction of future research.

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Most cited references 49

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Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma

Toni K. Choueiri, Thomas Powles, Mauricio Burotto … (2021)

The efficacy and safety of nivolumab plus cabozantinib as compared with those of sunitinib in the treatment of previously untreated advanced renal-cell carcinoma are not known.

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Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study.

Daniel Y C Heng, Wanling Xie, Meredith M Regan … (2009)

There are no robust data on prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (RCC) treated with vascular endothelial growth factor (VEGF) -targeted therapy. Baseline characteristics and outcomes on 645 patients with anti-VEGF therapy-naïve metastatic RCC were collected from three US and four Canadian cancer centers. Cox proportional hazards regression, followed by bootstrap validation, was used to identify independent prognostic factors for OS. The median OS for the whole cohort was 22 months (95% CI, 20.2 to 26.5 months), and the median follow-up was 24.5 months. Overall, 396, 200, and 49 patients were treated with sunitinib, sorafenib, and bevacizumab, respectively. Four of the five adverse prognostic factors according to the Memorial Sloan-Kettering Cancer Center (MSKCC) were independent predictors of short survival: hemoglobin less than the lower limit of normal (P < .0001), corrected calcium greater than the upper limit of normal (ULN; P = .0006), Karnofsky performance status less than 80% (P < .0001), and time from diagnosis to treatment of less than 1 year (P = .01). In addition, neutrophils greater than the ULN (P < .0001) and platelets greater than the ULN (P = .01) were independent adverse prognostic factors. Patients were segregated into three risk categories: the favorable-risk group (no prognostic factors; n = 133), in which median OS (mOS) was not reached and 2-year OS (2y OS) was 75%; the intermediate-risk group (one or two prognostic factors; n = 301), in which mOS was 27 months and 2y OS was 53%; and the poor-risk group (three to six prognostic factors; n = 152), in which mOS was 8.8 months and 2y OS was 7% (log-rank P < .0001). The C-index was 0.73. This model validates components of the MSKCC model with the addition of platelet and neutrophil counts and can be incorporated into patient care and into clinical trials that use VEGF-targeted agents.

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Sunitinib versus interferon alfa in metastatic renal-cell carcinoma.

Robert Motzer, Thomas E. Hutson, Piotr Tomczak … (2007)

Since sunitinib malate has shown activity in two uncontrolled studies in patients with metastatic renal-cell carcinoma, a comparison of the drug with interferon alfa in a phase 3 trial is warranted. We enrolled 750 patients with previously untreated, metastatic renal-cell carcinoma in a multicenter, randomized, phase 3 trial to receive either repeated 6-week cycles of sunitinib (at a dose of 50 mg given orally once daily for 4 weeks, followed by 2 weeks without treatment) or interferon alfa (at a dose of 9 MU given subcutaneously three times weekly). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, patient-reported outcomes, and safety. The median progression-free survival was significantly longer in the sunitinib group (11 months) than in the interferon alfa group (5 months), corresponding to a hazard ratio of 0.42 (95% confidence interval, 0.32 to 0.54; P<0.001). Sunitinib was also associated with a higher objective response rate than was interferon alfa (31% vs. 6%, P<0.001). The proportion of patients with grade 3 or 4 treatment-related fatigue was significantly higher in the group treated with interferon alfa, whereas diarrhea was more frequent in the sunitinib group (P<0.05). Patients in the sunitinib group reported a significantly better quality of life than did patients in the interferon alfa group (P<0.001). Progression-free survival was longer and response rates were higher in patients with metastatic renal-cell cancer who received sunitinib than in those receiving interferon alfa (ClinicalTrials.gov numbers, NCT00098657 and NCT00083889 [ClinicalTrials.gov]). Copyright 2007 Massachusetts Medical Society.

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Author and article information

Contributors

Luigi Napolitano: (View ORCID Profile)

Celeste Manfredi: (View ORCID Profile)

Savio Domenico Pandolfo: (View ORCID Profile)

Felice Crocetto: (View ORCID Profile)

Davide Arcaniolo: (View ORCID Profile)

Biagio Barone: (View ORCID Profile)

Journal

Title: Medicina

Abbreviated Title: Medicina

Publisher: MDPI AG

ISSN (Electronic): 1648-9144

Publication date Created: April 2023

Publication date (Electronic): April 15 2023

Volume: 59

Issue: 4

Page: 767

Article

DOI: 10.3390/medicina59040767

PubMed ID: 37109725

SO-VID: 09e86e0a-7b50-4b99-a433-e5af8709028e

License:

https://creativecommons.org/licenses/by/4.0/

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