Cytoreductive nephrectomy

In the era before targeted antiangiogenic therapies and immune checkpoint inhibitors, two randomized studies demonstrated an OS benefit in selected patients who underwent initial cytoreductive nephrectomy before the administration of interferon alfa.[5,6] However, there is evidence that undergoing cytoreductive nephrectomy before antiangiogenic therapy does not provide a survival benefit to patients with intermediate- and poor-risk disease. Cytoreductive nephrectomy for good-risk patients has not been studied in a randomized controlled trial in the era of targeted therapies and immunotherapy. The limited data available from retrospective nonrandomized studies suggest a benefit in good-risk patients in the current era of targeted therapies.

The CARMENA trial (NCT00930033) evaluated the effectiveness of cytoreductive nephrectomy before targeted therapy. The study reported no benefit for patients who underwent cytoreductive nephrectomy before receiving treatment with sunitinib, an oral antiangiogenic tyrosine kinase inhibitor.[7] This study enrolled only patients with intermediate- (57%) and poor-risk (43%) disease, whereas a previous retrospective study found that cytoreductive nephrectomy only benefited good- and intermediate-risk patients in the sunitinib era. Similarly, the positive trials in the interferon era were restricted to patients who were asymptomatic or minimally symptomatic, with a performance status rating of 0 or 1, according to the ECOG rating scale; these patients were also considered candidates for postoperative immunotherapy.

A multicenter analysis of 351 patients with metastatic renal cell carcinoma was conducted to assess the impact of cytoreductive nephrectomy. The study evaluated patients who received systemic therapy and compared outcomes of those who underwent cytoreductive nephrectomy with those who did not. The median OS was 38.1 months for patients who underwent nephrectomy compared with 16.4 months for those treated with systemic therapy alone (P = .03). However, the survival benefit was limited to patients with an ECOG performance status rating of 0 to 1 and good- or intermediate-risk disease.[8] Interpretation of the study is limited by selection bias because patients were not randomly assigned to the nephrectomy group. Whether there is a benefit from cytoreductive nephrectomy for patients who are not subsequently treated with systemic therapy has not been tested.

Randomized controlled trials of cytoreductive nephrectomy:

A randomized, controlled, noninferiority trial of 450 patients compared the outcomes of patients who received sunitinib alone with those who received cytoreductive nephrectomy followed by sunitinib. The trial was designed to enroll 576 individuals; therefore it was underpowered.[7] In this study, 43% of the patients had poor-risk disease and 57% had intermediate-risk disease.

Randomized controlled trials of interferon with or without preceding cytoreductive nephrectomy:

Two randomized studies demonstrated an OS benefit in selected patients who underwent initial cytoreductive nephrectomy before the administration of interferon alfa.[5,6]