Introduction:

Immune checkpoint inhibitors (ICI) were approved for treating metastatic renal cell carcinoma (mRCC) in 2015.  Current clinical use of cytoreductive nephrectomy (CN) is guided by extrapolation from studies using other classes of systemic therapy in mRCC.  We sought to evaluate survival outcomes, timing, and safety of combining CN with modern immunotherapy (IO) approaches for mRCC.

Methods:

We performed a population-based observational study using National Cancer Database (NCDB) data. From 96,329 renal cancer cases reported to the NCDB from 2015-2016, the final cohort for analysis included 391 surgical candidates diagnosed with clear cell mRCC who were treated with IO +/- CN and no other systemic therapies (Figure 1). Primary outcome was overall survival (OS) stratified by the performance of CN (CN+IO vs. IO alone).  Secondary outcomes included whether the timing of IO administration in relation to CN impacts OS, pathologic findings, and perioperative outcomes.

Results:

Of 391 patients included, 221 (56.5%) received CN+IO and 170 (43.5%) received IO only. Across a median follow-up of 14.7 months, patients who underwent CN+IO had significantly better OS (Figure 2; median NR vs. 11.6 mos.; HR 0.23 [95%CI 0.15-0.37], p<0.001), which was upheld on multivariable analyses.  IO administration before CN resulted in lower pT stage, Fuhrman grade, tumor size, and frequency of lymphovascular invasion compared to upfront CN.  Two of 20 patients (10%) undergoing CN post-IO with pT stage recorded achieved complete pathologic response in the primary tumor (pT0).  There were no positive surgical margins, 30-day readmissions, or prolonged inpatient length-of-stay in patients undergoing delayed CN.

Conclusion:

Using a large, national, population-based database, we provide the first report of survival outcomes in mRCC patients treated with CN combined with modern IO approaches. Our findings support an oncologic role for CN in the modern IO era and provide preliminary evidence regarding the timing and safety of CN relative to IO administration.

Funding: NIH/NCI