Impact of Previous Nephrectomy on Clinical Outcome of Metastatic Renal Carcinoma Treated With Immune-Oncology: A Real-World Study on Behalf of Meet-URO Group (MeetUro-7b)

Abstract

BackgroundImmune-Oncology (IO) improves Overall Survival (OS) in metastatic Renal Cell Carcinoma (mRCC). The prognostic impact of previous Cytoreductive Nephrectomy (CN) and radical nephrectomy (RN), with curative intent, in patients treated with IO is not well defined. The aim of our paper is to evaluate the impact of previous nephrectomy on outcome of mRCC patients treated with IO.Methods287 eligible patients were retrospectively collected from 16 Italian referral centers adhering to the MeetUro association. Patients treated with IO as second and third line were included, whereas patients treated with IO as first line were excluded. Kaplan–Meier method and log-rank test were performed to compare Progression Free Survival (PFS) and OS between groups. In our analysis, both CN and RN were included. The association between nephrectomy and other variables was analyzed in univariate and multivariate setting using the Cox proportional hazard model.Results246/287 (85.7%) patients had nephrectomy before IO treatment. Median PFS in patients who underwent nephrectomy (246/287) was 4.8 months (95%CI 3.9–5.7) vs 3.7 months (95%CI 1.9–5.5) in patients who did not it (HR log rank 0.78; 95%CI 0.53 to 1.15; p = 0.186). Median OS in patients who had previous nephrectomy (246/287) was 20.9 months (95%CI 17.6–24.1) vs 13 months (95%CI 7.7–18.2) in patients who did not it (HR log rank 0.504; 95%CI 0.337 to 0.755; p = 0.001). In the multivariate model, nephrectomy showed a significant association with OS (HR log rank 0.638; 95%CI 0.416 to 0.980), whereas gland metastases were still associated with better outcome in terms of both OS (HR log rank 0.487; 95%CI 0.279 to 0.852) and PFS (HR log rank 0.646; 95%CI 0.435 to 0.958).ConclusionsIO treatment, in patients who had previously undergone nephrectomy, was associated with a better outcome in terms of OS. Further prospective trials would assess this issue in order to guide clinicians in real word practice.

Effects of Cytoreductive Nephrectomy on Nivolumab Outcomes in Patients with Metastatic Clear Cell Renal Carcinoma: A Retrospective Observational Real-Life Data of Turkish Oncology Group

“…The signi cant difference in OS in the study of Stellato et al 23 , which was not found in our research, may be due to the exclusion of the patient group with early-stage partial and radical nephrectomy. In addition, since our study included only metastatic ccRCC patients at the time of diagnosis, the rate of patients with poor IMDC was much higher in our study (37.7% vs. 10.1%) than that in the study of Stellato et al 23 . Another reason for the lack of OS bene ts may be the inclusion of more patients with high risk.…”

“…Cytoreductive nephrectomy is recommended as palliative surgery to alleviate complaints such as pain, hematuria, and symptoms arising from paraneoplastic syndromes 22 . There are some studies in the literature that investigate the effects of nephrectomy on immunotherapy response, however therapeutic nephrectomy in non-metastatic disease and cytoreductive nephrectomy in the metastatic stage was evaluated together in these studies 16,17,23 . Upfront nephrectomy may have effects on survival.…”

“…In the long-term results of the CARMENA trial, longer overall survival results were obtained in patients with delayed nephrectomy 32 . Stellato et al 23 found that the IMDC risk group had a statistically signi cant predictive value in OS and PFS in immunotherapy response in patients who had previously undergone nephrectomy. These ndings are consistent with the results of our study, indicating that the IMDC risk group had a statistically signi cant predictive value in OS and TTD for nivolumab treatment response.…”

Predictive Factors Affecting Metastasis of Small Renal Mass and Its Prognostic Analysis

“… 15 , 16 Under the premise of immunotherapy, cytoreductive surgery can also benefit patients. 17 All of the patients we included have undergone surgery, so they cannot be compared with patients who have received systemic treatment alone. Moreover, patients with mSRM may be older and have obvious clinical manifestations because of treatment-seeking delay.…”

Do Metastatic Kidney Cancer Patients Benefit From Cytoreductive Nephrectomy? A Real-World Retrospective Study From the SEER Database

“…The recent study demonstrated that nivolumab plus ipilimumab has shown significant OS and response rate than sunitinib alone, which enables immune checkpoint blockade to be recommended as frontline therapy in the latest guideline ( 29 , 30 ). A recent real-world study showed that immune-oncology treatment was associated with a better OS in patients who had previously undergone CN ( 31 ). Therefore, with the rapid development of systemic treatment of mRCC, a more well-designed randomized study is warranted to investigate the role of CN under the new era of immune therapy.…”