Optimizing patient selection for adjuvant immunotherapy in high-risk non-metastatic renal cell carcinoma

Abstract Background Tyrosine kinase inhibitor-based adjuvant therapy showed no survival benefit in high-risk non-metastatic renal cell carcinoma (nmRCC). Five randomized immune-oncology checkpoint inhibitor trials are ongoing. We assessed the effect of stage, grade and histology on cancer-specific mortality (CSM) in candidates for one of the four North-American ongoing immunotherapy adjuvant trial in high-risk non-metastatic renal cell carcinoma (nmRCC). Patients and methods In SEER database (2001-2015), we identified surgically-treated nmRCC patients who met inclusion criteria either PROSPER RCC, CheckMate 914, KEYNOTE-564 or IMmotion010 trials. Kaplan-Meier and multivariable Cox regression models assessed ten-year CSM rates in the overall cohort according to stage, grade and histology characteristics, as well as in four generated random samples according to eligible patients for each of the four trials. Results Of 116,750 surgically-treated nmRCC patients, 18,559 (15.9%) fulfilled inclusion criteria of one of the four trials. The highest proportion of higher stage and grade combinations and sarcomatoid histology would have qualified for IMmotion010, followed by KEYNOTE-564, CheckMate 914 and PROSPER RCC. Multivariable Cox regression models demonstrated the most unfavorable prognosis for N1 G3/G4 (hazard ratio [HR] 11.5, p Conclusion Our findings indicate that adjuvant immunotherapy trials participation should predominantly be encouraged in patients with high grade T3, T4 and N1 stages, as well as any stage with sarcomatoid pathology.