Pathologic response after neoadjuvant therapy in renal cell carcinoma using irRVT criteria.

549 Background: Pathologic response after neoadjuvant therapy for renal cell carcinoma (RCC) lacks a standardized system that correlates with outcomes and captures immune-related histologic effects. This study evaluated clinical impact and pathologic response using immune-related residual viable tumor (irRVT) criteria—validated in other malignancies—among patients undergoing surgery for localized or metastatic RCC. Methods: A prospectively maintained RCC database was queried for patients undergoing surgery after systemic therapy. Pathology was re-reviewed to quantify %irRVT, defined as the proportion of residual viable tumor within the entire tumor bed, distinct from nonspecific necrosis and the regression bed consisting of immune-mediated cell death and immune activation components. Treatment details and clinical outcomes were reported based on degree of pathologic response. Survival in metastatic cases was estimated using the Kaplan-Meier method. Results: Thirty-seven patients were identified, with median follow-up of 21.7 mo after surgery. Early recurrence (≤6 mo) occurred in 11 patients (10 initially cM1), all demonstrating a tumor bed necrosis-to-regression ratio ≥1, a previously undescribed pattern. Radiographic and pathologic responses were significantly associated (p=0.015), though several cases showed discordance (Table 1). Partial nephrectomy was performed in 6 patients (one cM1) without positive margins or high-grade complications; median GFR declined from 56 to 47 mL/min/1.73 m². Localized RCC comprised 38% of the cohort (50% cT3–4). Patients received a median of 17 wk of IO and 14 wk of TKI; 43% achieved major pathologic response (irRVT < 10%). None progressed preoperatively or received adjuvant therapy; one recurred postoperatively. Among 23 metastatic cases, 48% demonstrated poor pathologic response (irRVT ≥ 50%), associated with shorter median post-operative PFS versus others (15.0 mo vs 31.7 mo, p = 0.048). Conclusions: irRVT criteria capture immune-related pathologic responses not reflected by radiographic or conventional pathologic criteria. Poor pathologic response correlated with shorter PFS. Neoadjuvant therapy was oncologically safe in localized RCC and preserved renal function. Further validation of irRVT as a prognostic marker is warranted. Degree of pathologic response based on immune-related residual viable tumor (irRVT) criteria. Radiographic response by RECIST 1.1 criteria. Major (<10%)n=13 Partial (10-49%) n=6 Poor (≥50%)n=18 Radiographic Response Partial Stable Progression 9 (69%)4 (31%)0 2 (33%)4 (67%)0 2 (11%)14 (78%)2 (11%) Progression after surgery None ≤6 months >6 months 9 (69%)1 (7.7%)3 (23%) 2 (33%)3 (50%)1 (17%) 9 (50%)7 (39%)2 (11%) Treatment Duration (m), (Med (Q1-Q3)) Immunotherapy Targeted Therapy (TKI) 4.9 (4.3-7.9)5.3 (3.2-7.0) 3.2 (2.3-8.2)4.1 (0.8-8.6) 5.8 (4.4-8.3)3.5 (1.8-6.0)