Propensity Score-Matched Analysis of Neoadjuvant vs. Adjuvant Therapy in Renal Cell Carcinoma

Objective: The aim was to compare outcomes in high-risk localized RCC (HRL-RCC) patients treated with adjuvant (AT) and neoadjuvant therapy (NT) utilizing a propensity score-matched model (PSM). Methods: We conducted a multicenter analysis (USA and Japan) for patients who underwent AT or NT. AT was defined as systemic therapy given postoperatively in the absence of metastases; NT was presurgical therapy in the setting of localized disease. AT and NT utilized included target molecular therapy (TMT) or immunotherapy (IO). The PSM model was generated using a nearest neighbor matching algorithm in a 1:2 ratio. The primary outcome was All-Cause Mortality (ACM); the secondary outcomes were Cancer-Specific Mortality (CSM) and recurrence. Cox regression multivariable analysis (MVA) was utilized to elucidate predictors of outcomes. Results: After PSM modeling, 311 patients were analyzed [adjuvant n = 221, 127 TMT vs. 94 IO; neoadjuvant n = 90, 61 TMT vs. 29 IO]; the median follow-up was 44 (IQR 20–74) months. MVA revealed AT as associated with increased ACM (HR = 1.97, p = 0.007), CSM (HR = 2.37, p = 0.007) and recurrence (HR 1.64, p = 0.02). Sub-analysis of the AT cohort revealed IO to be associated with decreased ACM (HR 0.59, p = 0.015). In the neoadjuvant cohort, TMT and IO were associated with decreased ACM (HR 0.49; p = 0.016; HR 0.32, p = 0.016, respectively) and CSM risk (HR 0.47, p = 0.036; HR 0.18, p = 0.017). Conclusions: Our findings suggest a potential advantage of NT in HRL-RCC. Adjuvant immunotherapy was associated with decreased risk of ACM, while in the neoadjuvant group, TMT and IO therapy had similar outcomes. Our findings call for the consideration of a clinical trial to compare the outcomes of AT vs. NT.