Comparison of Immediate vs Deferred Cytoreductive Nephrectomy in Patients With Synchronous Metastatic Renal Cell Carcinoma Receiving Sunitinib

Abstract

patients with primary metastatic renal cell carcinoma (mRCC) have been offered cytoreductive nephrectomy (CN) followed by targeted therapy, but the optimal sequence of surgery and systemic therapy is unknown. OBJECTIVE To examine whether a period of sunitinib therapy before CN improves outcome compared with immediate CN followed by sunitinib. DESIGN, SETTING, AND PARTICIPANTS This randomized clinical trial began as a phase 3 trial on July 14, 2010, and continued until March 24, 2016, with a median follow-up of 3.3 years and a clinical cutoff date for this report of May 5, 2017. Patients with mRCC of clear cell subtype, resectable primary tumor, and 3 or fewer surgical risk factors were studied. INTERVENTIONS Immediate CN followed by sunitinib therapy vs treatment with 3 cycles of sunitinib followed by CN in the absence of progression followed by sunitinib therapy. MAIN OUTCOMES AND MEASURES Progression-free survival was the primary end point, which needed a sample size of 458 patients. Because of poor accrual, the independent data monitoring committee endorsed reporting the intention-to-treat 28-week progression-free rate (PFR) instead. Overall survival (OS), adverse events, and postoperative progression were secondary end points. RESULTS The study closed after 5.7 years with 99 patients (80 men and 19 women; mean [SD] age, 60 [8.5] years). The 28-week PFR was 42% in the immediate CN arm (n = 50) and 43% in the deferred CN arm (n = 49) (P = .61). The intention-to-treat OS hazard ratio of deferred vs immediate CN was 0.57 (95% CI, 0.34-0.95; P = .03), with a median OS of 32.4 months (95% CI, 14.5-65.3 months) in the deferred CN arm and 15.0 months (95% CI, 9.3-29.5 months) in the immediate CN arm. In the deferred CN arm, 48 of 49 patients (98%; 95% CI, 89%-100%) received sunitinib vs 40 of 50 (80%; 95% CI, 67%-89%) in the immediate arm. Systemic progression before planned CN in the deferred CN arm resulted in a per-protocol recommendation against nephrectomy in 14 patients (29%; 95% CI, 18%-43%). CONCLUSIONS AND RELEVANCE Deferred CN did not improve the 28-week PFR. With the deferred approach, more patients received sunitinib and OS results were higher. Pretreatment with sunitinib may identify patients with inherent resistance to systemic therapy before planned CN. This evidence complements recent data from randomized clinical trials to inform treatment decisions in patients with primary clear cell mRCC requiring sunitinib.

New prognostic model for synchronous metastatic renal cell carcinoma

“…2 Another randomized study, the SURTIME trial, showed that deferred nephrectomy after three cycles of sunitinib had relatively longer OS than immediate nephrectomy (32.4 vs 15.0 months), because more patients received sunitinib in the deferred nephrectomy group. 17 Furthermore, a number of retrospective studies showed the benefit of cytoreductive nephrectomy, including the present study. 12,13,15,[18][19][20][21] Thus, cytoreductive nephrectomy is still expected to prolong survival, especially in patients with systemic therapy and long survival expectancy, so that the appropriate patient selection for nephrectomy is warranted.…”

Recommandations CCAFU sur la prise en charge des cancers de l’appareil urogénital en période d’épidémie au Coronavirus COVID-19

“…Leur pronostic est péjoratif, même lorsqu'elles sont opérées rapidement, particulièrement en cas de thrombus veineux [9]. Il est donc recommandé d'opérer ces tumeurs en priorité ; • concernant la néphrectomie cytoréductrice, les essais Carmena et Surtime indiquent que le traitement médical seul n'est pas inférieur à la néphrectomie associée au traitement médical et que la néphrectomie différée n'est pas associée à une moins bonne survie [10,11] Le bénéfice du standard actuel de traitement reposant sur l'association ipilimumab-nivolumab doit être mis en balance avec le risque de toxicité sévère dans le contexte de réduction de l'accès à un service de réanimation L'emploi du sunitinib par défaut est sub-optimal mais peut se discuter dans ce contexte Les patients de pronostic intermédiaire avec faible charge tumorale et asymptomatiques pourraient être traités par TKI Pour les patients de mauvais pronostic et en mauvais état général (PS ≥ 2), un traitement palliatif exclusif peut être privilégié les patients de bon pronostic. Tous ces éléments incitent à prioriser : soit la surveillance en cas de faible volume tumoral, soit le traitement médical premier et la discussion secondaire de la chirurgie en fonction de l'évolutions du patient et de l'épidémie ;…”

Current status of prognostic factors in patients with metastatic renal cell carcinoma

“…36 In addition, another randomized trial, the SURTIME trial, which compared mRCC patients treated with sunitinib therapy before CN with those with immediate CN followed by sunitinib, showed that there was no significant difference of the progression-free rate between these two groups. 37 The effect of presurgical sunitinib treatment might provide some information on predicting the benefit of CN. As the number of new agents is increasing, the impact of CNx and patients' selection for CNx needs to be discussed further.…”