The phase 3 CARMENA trial analyzed the effects of cytoreductive nephrectomy (CN) followed by sunitinib against sunitinib alone in patients with metastatic renal cell carcinoma (mRCC). The trial found that sunitinib alone was not inferior to CN, causing the role and timing of CN to become harder to define.
Immunotherapy (IO) administered as a part of combination therapies such as IO-VEGF TKIs have improved outcomes for patients with first-line mRCC. At the 2023 Kidney Cancer Research Summit, researchers summarized the pathological and survival outcomes of patients with mRCC treated with CN after IO-based perioperative treatments.
The retrospective analysis included 51 patients with mRCC who had received IO-based therapies and were undergoing cytoreductive nephrectomy at the University of Texas Southwestern between April 2016 and October 2022. The primary endpoint was pathologic tumor size reduction and downstaging of the primary tumor. Secondary endpoints included progression-free survival (PFS) and overall survival (OS).
The median age of the patient group was 62 years (36-86, 76.5% male) with a median follow-up of 21 months. IO-IO treatments were administered to 63% of patients (n=32), while 21.6% received IO-VEGF combinations (n=11). The remaining patients received IO monotherapy.
A total of 38 (74.5%) patients received treatment prior to surgery, while 13 (25.5%) patients had up-front cytoreductive surgery. At the start of IO therapy, 86% of patients were treatment-naïve, and the mean IO cycles before surgery were 6.7 (1-39). Neoadjuvant IO-based treatment was found to reduce the median tumor size from 10cm at pre-treatment to 7.5cm after treatment.
Pathologic T downstaging was seen in 42% (n=16) of patients, and 11% (n=4) had pT0 disease. Thrombus downstaging occurred in 13% (n=5) of patients. PFS (HR=0.7, 95% CI 0.29-1.98, P=.58) and OS (HR 0.4, 95% CI 0.13-1.57, P=0.21) rates were not statistically significant, but trended better for patients that received neoadjuvant therapy. After neoadjuvant treatment, 2 patients with synchronous bilateral renal masses underwent staged radical nephrectomy and partial nephrectomy.
Neoadjuvant IO treatment was found to reduce tumor size and pathologic necrosis at the time of nephrectomy. PFS and OS were similar in patients who received either upfront IO-based therapy or cytoreductive nephrectomy before systemic treatment. Further studies are needed with larger cohorts to validate this data, and randomized patient cohorts are currently ongoing to determine the timing and outcomes of cytoreductive nephrectomy for patients with mRCC.