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 [adjuvantn= 221, 127 TMT vs. 94 IO; neoadjuvantn= 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.
目的：本研究旨在利用倾向评分匹配模型，比较接受辅助治疗与新辅助治疗的高危局限性肾细胞癌患者的临床结局。方法：我们对接受辅助治疗或新辅助治疗的患者进行了多中心（美国与日本）分析。辅助治疗定义为术后无转移状态下进行的全身性治疗；新辅助治疗指局限性病变阶段的术前治疗。两组治疗方案均包含靶向分子治疗或免疫治疗。采用最近邻匹配算法以1:2比例构建倾向评分匹配模型。主要研究终点为全因死亡率；次要终点包括癌症特异性死亡率及复发率。通过Cox回归多变量分析明确结局的预测因素。结果：经倾向评分匹配后，共纳入311例患者进行分析[辅助治疗组221例（靶向治疗127例，免疫治疗94例）；新辅助治疗组90例（靶向治疗61例，免疫治疗29例）]，中位随访时间为44个月（四分位距20-74个月）。多变量分析显示辅助治疗与全因死亡率（风险比=1.97，p=0.007）、癌症特异性死亡率（风险比=2.37，p=0.007）及复发率（风险比=1.64，p=0.02）升高相关。辅助治疗亚组分析表明免疫治疗可降低全因死亡率（风险比=0.59，p=0.015）。在新辅助治疗组中，靶向治疗与免疫治疗均能降低全因死亡率（风险比分别为0.49，p=0.016；0.32，p=0.016）及癌症特异性死亡风险（风险比分别为0.47，p=0.036；0.18，p=0.017）。结论：本研究提示新辅助治疗在高危局限性肾细胞癌中可能具有潜在优势。辅助免疫治疗可降低全因死亡风险，而新辅助治疗组中靶向治疗与免疫治疗疗效相当。研究结果提示有必要开展临床试验以比较辅助治疗与新辅助治疗的临床结局。
Propensity Score-Matched Analysis of Neoadjuvant vs. Adjuvant Therapy in Renal Cell Carcinoma
肿瘤(癌症)患者之家