Flammia Rocco Simone, Tuderti Gabriele, Bologna Eugenio, Minore Antonio, Proietti Flavia, Licari Leslie Claire, Mastroianni Riccardo, Bove Alfredo Maria, Anceschi Umberto, Brassetti Aldo, Ferriero Maria Consiglia, Guaglianone Salvatore, Chiacchio Giuseppe, Calabrò Fabio, Leonardo Costantino, Simone Giuseppe
Department of Urology, IRCCS "Regina Elena" National Cancer Institute, 00128 Rome, Italy.
Department of Surgery, Sapienza University of Rome, 00161 Rome, Italy.
J Clin Med. 2024 Sep 14;13(18):5466. doi: 10.3390/jcm13185466.
Check-Mate 274 has demonstrated the disease-free survival (DFS) benefit of adjuvant nivolumab in surgically treated muscle-invasive bladder cancer (MIBC). Since immunotherapy represents an expensive treatment with potential side effects, a better understanding of patient-specific risks of disease progression might be useful for clinicians when weighing the indication for adjuvant nivolumab. To identify the criteria for risk stratification of disease progression among MIBC patients eligible for adjuvant nivolumab. A single-institution, prospectively maintained database was queried to identify patients eligible for adjuvant nivolumab according to Check-Mate 274 criteria. To account for immortal bias, patients who died or were lost to follow-up within 3 months of undergoing a radical cystectomy (RC) were excluded. Kaplan-Meier and Cox regression analyses addressed DFS, defined as the time frame from diagnosis to the first documented recurrence or death from any cause, whichever occurred first. Regression tree analysis was implemented to identify criteria for risk stratification. Between 2011 and 2022, 304 patients were identified, with a median follow-up of 50 (IQR 24-72) months. After multivariable adjustment, including NAC as a potential confounder, higher CCI (HR 1.56, 95%CI 1.10-2.21, = 0.013), T stage (HR 2.06, 95%CI 1.01-4.17, = 0.046), N stage (HR 1.73, 95%CI 1.26-2.38, = 0.001) and presence of LVI (HR 1.52, 95%CI 1.07-2.15, = 0.019) increased the risk of disease recurrence or death. Finally, a two-tier classification was developed. Here, five-year DFS rates were 56.1% vs. 18.1 for low vs. high risk (HR: 2.54, 95%CI 1.79-3.62, < 0.001). The current risk classification, if externally validated on larger samples, may be useful when weighing the risk and benefit of adjuvant nivolumab treatment and making patients more aware about their disease and about the need for additional treatment after RC.
Check-Mate 274研究已证实，辅助性纳武利尤单抗用于手术治疗的肌层浸润性膀胱癌（MIBC）可带来无病生存期（DFS）获益。鉴于免疫治疗是一种昂贵且有潜在副作用的治疗方法，在权衡辅助性纳武利尤单抗的适应证时，更好地了解患者特定的疾病进展风险可能对临床医生有用。旨在确定符合辅助性纳武利尤单抗治疗条件的MIBC患者疾病进展风险分层的标准。查询了一个单机构前瞻性维护的数据库，以根据Check-Mate 274标准确定符合辅助性纳武利尤单抗治疗条件的患者。为了避免不朽偏倚，排除了在接受根治性膀胱切除术（RC）后3个月内死亡或失访的患者。采用Kaplan-Meier法和Cox回归分析评估DFS，DFS定义为从诊断到首次记录的复发或任何原因导致的死亡的时间间隔，以先发生者为准。实施回归树分析以确定风险分层标准。2011年至2022年期间，共纳入304例患者，中位随访时间为50（IQR 24 - 72）个月。在多变量调整后，将新辅助化疗（NAC）作为潜在混杂因素纳入分析，结果显示，较高的Charlson合并症指数（CCI）（HR 1.56，95%CI 1.10 - 2.21，P = 0.013）、T分期（HR 2.06，95%CI 1.01 - 4.17，P = 0.046）、N分期（HR 1.73，95%CI 1.26 - 2.38，P = 0.001）和淋巴管浸润（LVI）的存在（HR 1.52，95%CI 1.07 - 2.15，P = 0.019）均增加了疾病复发或死亡的风险。最后，制定了一个两级分类法。在此分类法中，低风险组与高风险组的五年DFS率分别为56.1%和18.1%（HR：2.54，95%CI 1.79 - 3.62，P < 0.001）。如果在更大样本上进行外部验证，当前的风险分类在权衡辅助性纳武利尤单抗治疗的风险和获益以及让患者更清楚了解其疾病和RC术后额外治疗需求时可能会有用。
