Approximately 65,000 new cases of renal cell carcinoma (RCC) were diagnosed in the United States in 2018, with 30%-35% initially presenting with either regional or distant disease (nonlocalized).1 Nonlocalized disease has significantly worse 5-year survival outcomes (regional 69%, distant 12%) compared with localized disease (93%).1 The treatment options for those patients with metastatic RCC (mRCC) can be challenging compared with those with localized disease. One of the treatment mainstays in mRCC includes cytoreductive nephrectomy (CRN), in which patients undergo a nephrectomy followed by systemic treatment, which has typically included interferon and interleukin-2–based therapies.2 The exact mechanisms to support this treatment option have not been fully elucidated, but could include a compromised feedback loop between the primary RCC and its metastases after nephrectomy along with removal of the nidus of future metastases after removal of the primary.2

Most of the supportive CRN data had come from two clinical trials published in 2001. In the first study, published in the The New England Journal of Medicine, patients who underwent radical nephrectomy followed by therapy with interferon alfa-2b had longer median overall survival (OS) compared with those patients with mRCC receiving interferon alfa-2b therapy alone (11.1 months vs 8.1 months, P =.05).3  This difference in median OS was independent of the metastatic site and performance status.

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The second study, published in The Lancet, showed that patients undergoing radical nephrectomy followed by interferon-alfa–based therapy (given 3 times per week) had longer time to progression (5 months vs 3 months; hazard ratio [HR], 0.60; 95% CI, 0.36-0.97) and median duration of survival (17 months vs 7 months; HR, 0.54; 95% CI, 0.31-0.94) when compared with patients receiving interferon-alfa–based therapy alone.4

Newer, more innovative therapies such as tyrosine kinase inhibitors (TKIs) and immunotherapy agents (eg, checkpoint inhibitors) have since been developed, therefore offering more targeted medical options. This has led to interest in reexamining the role of CRN in mRCC within a different, more targeted treatment landscape than perhaps was seen in the late 1990s and early 2000s. More recent data has been published evaluating these types of scenarios, including the CARMENA and SURTIME clinical trials, although both studies had challenges recruiting the planned number of patients and therefore, may not be entirely representative of all clinical outcomes.