61 Differential Pattern of Disease Recurrence in Resected Renal Cell Carcinoma Patients Treated with Adjuvant Pembrolizumab Versus Observation: A Propensity Score-Weighted Analysis

Background Adjuvant pembrolizumab is the standard of care for patients with resected intermediate-high-risk, high-risk, and M1 no evidence of disease (NED) renal cell carcinoma (RCC). Nevertheless, approximately 30% of treated patients experience disease recurrence. Data on patterns of disease recurrence in this setting are still lacking. Methods We conducted a multicenter retrospective analysis of patients with resected RCC who experienced disease recurrence. Patients with resected RCC who met the eligibility criteria of the KEYNOTE-564 and LITESPARK-022 trials were included. Patients receiving adjuvant pembrolizumab were compared with those managed with observation after surgery. Patterns of disease recurrence, including metastatic burden at recurrence, were evaluated between groups and categorized as high-burden recurrence (>5 metastases) or oligometastatic recurrence (≤5 metastases). Comparisons of categorical variables were performed using Fisher’s exact test. Associations between prior adjuvant therapy and metastatic burden at recurrence were evaluated using ordinal logistic regression models adjusted for age, nephrectomy type, sarcomatoid differentiation, rhabdoid differentiation, and KEYNOTE-564 risk category, also incorporating center-specific random effects to account for inter-institutional heterogeneity. A complementary propensity score-weighted analysis using inverse probability of treatment weighting (IPTW) was performed to account for baseline differences between treatment groups. Results Data from 141 patients with RCC who underwent resection and had disease recurrence were retrospectively collected. After surgery, 93 patients were managed with initial observation, whereas 48 received adjuvant pembrolizumab. Baseline characteristics of patients are described in Table 1. Oligometastatic recurrence was the most frequent pattern of relapse, occurring in 93 of 141 patients (66%). However, this pattern was more common in the adjuvant pembrolizumab group compared with the observation group: 85% (41/48) versus 56% (52/93), corresponding to a significantly higher odds of oligometastatic relapse in the pembrolizumab cohort (OR 4.62, p = 0.001). In addition, patients treated with adjuvant pembrolizumab had lower odds of high-burden metastatic recurrence than those on observation: 12% (6/48) versus 39% (36/93), respectively (OR 0.23, p = 0.0016). In the adjusted model, prior treatment with adjuvant pembrolizumab was independently associated with a significantly reduced risk of high-burden metastatic disease at recurrence (OR 0.46, 95% CI 0.25-0.84; p = 0.012). These findings remained consistent after adjustment for baseline differences between treatment groups using IPTW. In the propensity-weighted analysis, adjuvant pembrolizumab remained associated with a significantly lower risk of high-burden metastatic recurrence (OR 0.47, 95% CI 0.26-0.85; p = 0.0012). Lung metastases were more frequent in the observation group compared with the adjuvant pembrolizumab group: 61% (57/93) versus 41.3% (20/48); OR 2.49, p = 0.022). Conclusions Adjuvant pembrolizumab was associated with a more favorable pattern of recurrence in resected RCC, characterized by reduced high-burden metastatic disease and fewer lung metastases.