Widmar Maria, McCain Mason, Mishra Meza Akriti, Ternent Charles, Briggs Andrew, Garcia-Aguilar Julio
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.
J Clin Oncol. 2025 Feb 20;43(6):672-681. doi: 10.1200/JCO.24.00681. Epub 2024 Oct 31.
The clinical efficacy of total neoadjuvant therapy (TNT) followed by selective nonoperative management (NOM) for locally advanced rectal cancer (LARC) was examined in the Organ Preservation for Rectal Adenocarcinoma (OPRA) trial. We investigated the cost and quality-of-life implications of adopting this treatment approach.
We analyzed clinical, cost, and quality-of-life outcomes for TNT with selective NOM in comparison with chemoradiotherapy (CRT)-surgery-adjuvant chemotherapy (standard of care [SOC]) using data from OPRA, prospective cohorts, and published studies. Cost-effectiveness was evaluated over varying willingness-to-pay thresholds, and sensitivity analyses evaluated cost-effectiveness for different surgical contexts and SOC variants as well as a 10-year time horizon.
SOC was dominated by TNT with selective NOM in the base case analysis. TNT in which CRT was followed by consolidation chemotherapy (CNCT) was the least costly at $89,712 in Medicare proportionate US dollars (MP$), followed by TNT in which induction chemotherapy was followed by CRT (INCT) at MP$90,259 and SOC at MP$98,755. INCT was the preferred strategy, with 4.56 quality-adjusted life years, followed by CNCT at 4.42 and SOC at 4.29. TNT with selective NOM dominated SOC in all sensitivity analyses except when SOC omitted adjuvant chemotherapy without an impact on disease-free survival. CNCT was more cost effective than SOC when the proportion of patients entering NOM after TNT was ≥22% or ≥43%, for SOC with and without adjuvant therapy, both well below the rates seen in OPRA.
TNT with selective NOM is cost effective. The cost-effectiveness of CNCT with NOM relative to SOC is dependent on CNCT being made available to a sufficiently large proportion of patients with LARC. Additional analyses are needed to validate these findings from a societal perspective and in the context of other emerging treatment paradigms for LARC.
在直肠腺癌器官保留（OPRA）试验中，研究了全新辅助治疗（TNT）联合选择性非手术治疗（NOM）用于局部晚期直肠癌（LARC）的临床疗效。我们调查了采用这种治疗方法对成本和生活质量的影响。
我们使用来自OPRA、前瞻性队列和已发表研究的数据，分析了TNT联合选择性NOM与放化疗（CRT）-手术-辅助化疗（标准治疗 [SOC]）的临床、成本和生活质量结果。在不同的支付意愿阈值下评估成本效益，敏感性分析评估了不同手术背景和SOC变体以及10年时间范围内的成本效益。
在基础病例分析中，SOC被TNT联合选择性NOM所主导。先进行CRT然后巩固化疗（CNCT）的TNT成本最低，按医疗保险比例美元（MP$）计算为89,712美元，其次是先进行诱导化疗然后CRT（INCT）的TNT，为MP$90,259，SOC为MP$98,755。INCT是首选策略，有4.56个质量调整生命年，其次是CNCT，为4.42个，SOC为4.29个。除了SOC省略辅助化疗且对无病生存期无影响的情况外，TNT联合选择性NOM在所有敏感性分析中都优于SOC。当TNT后进入NOM的患者比例≥22%或≥43%时，对于有和没有辅助治疗的SOC，CNCT比SOC更具成本效益，这两个比例均远低于OPRA中的观察率。
TNT联合选择性NOM具有成本效益。CNCT联合NOM相对于SOC的成本效益取决于有足够比例的LARC患者能够接受CNCT。需要进行额外的分析，从社会角度以及在LARC的其他新兴治疗模式背景下验证这些发现。
