Analysis suggests survival improved when cytoreductive nephrectomy added to immunotherapy in mRCC

A pooled analysis presented during the 2020 Society of Urologic Oncology Annual Meeting suggested that cytoreductive nephrectomy improved survival in patients with metastatic renal cell carcinoma (mRCC) receiving either immune checkpoint inhibitor or targeted therapy regimens.¹

The findings indicated that cytoreductive nephrectomy had the greatest impact on survival outcomes among patients receiving systemic immunotherapy.

The investigators assessed the effect of cytoreductive nephrectomy by searching PubMed and conference proceedings of relevant medical societies to identify observational cohort studies for patients receiving either targeted therapy or immunotherapy.

The primary objective of the study was to assess the benefit of cytoreductive nephrectomy relative to the newer area of immunotherapy regimens utilizing checkpoint inhibitors.

Studies were limited to those where the investigators were able to identify analyses of the effect of cytoreductive nephrectomy in patients receiving targeted therapy and immunotherapy from the same dataset.

From the 280 search results, 3 relevant studies were identified. Two studies reported comparisons of cytoreductive nephrectomy with systemic therapy and systemic therapy alone using the Nation Cancer Database, while the third utilized the International Metastatic RCC Database Consortium.

A pooled analysis of these studies indicated that there was improved survival with cytoreductive nephrectomy in both the targeted therapy cohorts (n = 2; HR, 0.52; 95% CI, 0.46-0.59; I² = 80%) and the immunotherapy cohorts (n = 2; HR, 0.28; 95% CI, 0.16-0.49; I² = 21%), with a significantly stronger association in the immunotherapy groups (P = 0.04; I² = 77%).

The value of cytoreductive nephrectomy was called into question following the results of the CARMENA trial, which failed to demonstrate a benefit of cytoreductive nephrectomy among patients receiving sunitinib (Sutent).²

While that trial showed that patients receiving sunitinib alone had a numerically improved median overall survival compared to those patients receiving cytoreductive nephrectomy plus sunitinib (18.4 months vs 13.9 months; HR, 0.89; 95% CI, 0.71-1.10), researchers at the time noted that the combination approach might still be applied to select subgroups of patients.

While the current study was limited to observational data, the investigators believed the results of the CARMENA trial do not preclude a benefit of cytoreductive nephrectomy for patients when combined with current immunotherapy-based regimens.

They noted that ongoing studies specifically evaluating cytoreductive nephrectomy in combination with immunotherapy-based treatment should help clarify the role of cytoreductive nephrectomy in current practice settings.

References

1. Hall ME, Bhindi B, Luckenbaugh AN, et al. Cytoreductive nephrectomy: are conclusions from the targeted therapy era valid in the checkpoint inhibitor era? Presented at: 21st Annual Meeting of the Society for Urologic Oncology; December 3, 2020. Poster 85.

2. Méjean A, Ravaud A, Thezenas S, et al. Sunitinib alone or after nephrectomy in metastatic renal-cell carcinoma. N Engl J Med. 2018;379(5):417-427. doi: 10.1056/NEJMoa1803675