Response assessment of patients with locally advanced renal cell carcinoma receiving prior systemic therapy.

[BACKGROUND] Locally advanced renal cell carcinoma (RCC) without distant metastases remains challenging to treat surgically, especially when venous tumor thrombus is present. Neoadjuvant checkpoint inhibitor (CPI) and tyrosine kinase inhibitor (TKI) therapy may downstage tumors and improve resectability, but evidence is limited. This study evaluated radiographic and pathological responses, surgical feasibility, and safety following preoperative systemic therapy.

[METHODS] This single-center retrospective analysis of 17 patients with non-metastatic RCC who received ≥ 1 month of CPI, TKI, or CPI + TKI before nephrectomy. Tumor stage, radiographic tumor/thrombus reduction, pathological viable tumor percentage, surgical outcomes, complications by Clavien-Dindo, and disease-free survival (DFS) were collected.

[RESULTS] Median pretreatment tumor diameter was 9.1 cm; 71% had venous tumor thrombus. Most patients (88%) received CPI + TKI. Median treatment duration was 7 months. Median radiographic tumor reduction was 27.1%; 50% of thrombus-bearing patients showed Mayo level reduction. Median viable tumor content was 30%; 17.6% achieved ypT0. T-stage downstaging occurred in 53%. Surgery was feasible in all cases; 17.6% experienced Clavien-Dindo grade ≥ III complications, mostly with thrombus resections. Median DFS was 28 months. No correlation between radiographic and pathological response was observed. Limitations include retrospective single-center design, small sample size, and limited follow-up/events, restricting generalizability and survival analyses.

[CONCLUSION] Preoperative CPI + TKI therapy in selected non-metastatic RCC patients is associated with measurable tumor and thrombus regression without compromising surgical safety. These findings support further prospective trials to clarify long-term oncologic benefit and identify predictors of response to integrate neoadjuvant therapy into multidisciplinary RCC care.