PD-1/PD-L1 inhibitors combined with vascular endothelial growth factor (VEGF) inhibitors have shown survival benefits in advanced renal cell carcinoma (RCC). However, the potential role of perioperative application in localized RCC remains unclear. The KEYNOTE-564 trial demonstrated that adjuvant pembrolizumab improved disease-free survival (DFS) in high-risk clear cell RCC (ccRCC) patients, though subgroup analyses suggested that not all patients derived benefit. Therefore, this study investigates the efficacy and safety of adjuvant tislelizumab in combination with TKI in ccRCC patients with a very high risk of recurrence after nephrectomy.

This retrospective study included 15 patients with very high-risk ccRCC (pT3/pT4Nx/N0M0, pTanyN+M0, or pT2Nx/N0M0 with nuclear grade ≥3, or stage M1 with no evidence of disease [NED]) who received adjuvant tislelizumab with TKI post-surgery from August 2021 to September 2024. Data on demographics, clinical characteristics, surgical outcomes, prognostic factors, and safety were collected and analyzed. The primary endpoint was DFS, with secondary endpoints including overall survival and safety.

The 15 patients had a median age of 57 years (interquartile range 32–71), with 10 (67%) male. Most patients had pT3 (73%) and pN0 (60%) disease, and 13% had M1 NED status. After a median follow-up of 15.5 months (range 5–36), the primary efficacy endpoint of DFS was not reached. The median treatment duration was 9.5 months (range 3–14) for tislelizumab and 6 months (range 3–8) for TKI. The 2-year and 1-year DFS rates were 93.8% (95% CI: 63.2–99.01%) and 84.4% (95% CI: 49.3–96%), respectively. Treatment-related adverse events (TRAEs) occurred in 92% of patients, with grade 3–4 TRAEs in 30%. The most common grade 3–4 TRAEs were leukopenia and hypertension. No treatment-related deaths were reported.

Adjuvant tislelizumab combined with TKI showed promising antitumor activity and a manageable safety profile in very high-risk ccRCC patients.