Multicenter randomized trial of deferred cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma receiving checkpoint inhibitors: the NORDIC-SUN-Trial.

BACKGROUND: Primary tumor removal by cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma patients has been investigated in the context of various treatment regimens. Two randomized controlled trials investigated the role and timing of cytoreductive nephrectomy in the era of targeted therapy and demonstrated that upfront nephrectomy should no longer be performed when patients require systemic therapy. Superiority of checkpoint immunotherapy agents has led to a paradigm change from targeted therapies to immunotherapy-based first-line treatment in patients with primary metastatic disease; thus, deferred cytoreductive nephrectomy needs to be verified in the immunotherapy setting. Furthermore, a need exists for personalizing treatment choices for the individual patient to avoid unnecessary overtreatment. METHODS/DESIGN: To explore the impact of cytoreductive nephrectomy in this patient group receiving checkpoint immunotherapy, we initiated a randomized, controlled trial comparing deferred cytoreductive nephrectomy with no surgery. The trial integrates a comprehensive translational research program with specimen sampling for biomarker analysis. DISCUSSION: The trial aims to show that deferred cytoreductive nephrectomy improves overall survival in patients with synchronous metastatic renal cell carcinoma, and furthermore, to identify relevant biomarkers for personalized renal cancer management. TRIAL REGISTRATION: ClinicalTrials.gov NCT03977571 June 6, 2019.

A case of metastatic renal cell carcinoma successfully treated with deferred cytoreductive nephrectomy following lenvatinib plus pembrolizumab combination therapy.

Introduction: Combination therapy using immuno-oncology drugs with tyrosine kinase inhibitors is increasingly important in the therapeutic strategy for metastatic renal cell carcinomas. Here, we report a case of metastatic renal cell carcinoma that was successfully treated with deferred cytoreductive nephrectomy following lenvatinib plus pembrolizumab combination therapy. Case presentation: A 49-year-old man was referred to our hospital with a diagnosis of advanced right kidney cancer with multiple lung metastases (cT3aN0M1). The size of the primary tumor was so huge that it exceeded 20 cm in diameter, pushing the liver and intestines to the left. After administration of lenvatinib and pembrolizumab combination as first-line treatment, all the metastatic lung lesions disappeared, and the primary lesion shrank significantly. Robot-assisted radical nephrectomy was successfully performed, resulting in complete surgical remission. Conclusion: Deferred cytoreductive nephrectomy following a lenvatinib plus pembrolizumab combination is a useful therapeutic strategy for achieving complete remission of metastatic renal cell carcinomas.

Deliberation on Deferred Cytoreductive Nephrectomy and Postoperative Treatment for Advanced Renal Cell Carcinoma: A Case Report.

In a rare case, free from systemic therapy, deferred cytoreductive nephrectomy was implemented in treating an advanced renal cell carcinoma with liver, lung, and splenic colon metastases. A 59-year-old man diagnosed with advanced renal cell carcinoma underwent deferred cytoreductive nephrectomy due to a partial response to systemic treatment after a period of 1 year. After the surgery, no additional treatment was implemented. Furthermore, after 10 months, the patient had no recurrence of renal cell carcinoma. Through a review of this case and deferred cases in the current literature, we could emphasize the importance of image evaluation and pathological findings as an indication for surgery and subsequent treatment options. However, there is room for debate with regards to the indications for deferred cytoreductive nephrectomy as well as a therapeutic strategy after the surgery. This report discusses the significance of deferred cytoreductive nephrectomy in terms of prognosis and quality-of-life improvement in advanced renal cancer.

Expression of tertiary lymphoid structure in deferred cytoreductive nephrectomy of metastatic renal cell carcinoma treated with nivolumab plus ipilimumab.

INTRODUCTION: Tertiary lymphoid structure expression and immune checkpoint inhibitors have been attracting attention, and their relationship with renal cell carcinoma is controversial. CASE PRESENTATION: Two patients with nivolumab plus ipilimumab treatment response for metastatic renal cell carcinoma underwent cytoreductive nephrectomy and regional lymph node dissection. In both cases, the renal tumor site expressed tertiary lymphoid structures. Despite the absence of treatment after a deferred cytoreductive nephrectomy and the short postoperative observation period, the patients still survived. CONCLUSION: Tertiary lymphoid structures were expressed in deferred cytoreductive nephrectomy specimen in cases treated with nivolumab plus ipilimumab.