Kanani Arezo, Veen Torhild, Lea Dordi, Zaharia Claudia, Watson Martin, Alexeeva Marina, Thorsen Kenneth, Søreide Kjetil
Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway.
Gastrointestinal Translational Research Unit, Molecular Laboratory, Stavanger University Hospital, Stavanger, Norway.
Ann Surg Oncol. 2025 May;32(5):3068-3077. doi: 10.1245/s10434-024-16755-y. Epub 2024 Dec 30.
Trials on neoadjuvant immunotherapy in operable colon cancer with deficient mismatch repair (dMMR) reported high pathological response rates in the surgical specimen, but long-term survival is not known. Neoadjuvant immunotherapy as a stand-alone therapy without subsequent radical surgery is currently not investigated in colon cancer.
The aim of this study was to model outcomes between trial data and real-world patients after surgery.
We conducted a comparative modeling study between prospective trial data (NICHE-1) and a prospective, population-derived, translational cohort study (ACROBATICC) of patients with operable colon cancer and microsatellite instability (MSI) status. Comparison was performed across immune-cell infiltrates, stages, MSI, and patient demographics for adverse events, reported oncological outcomes, and modeling numbers needed to treat (NNT) to prevent recurrence.
Patient characteristics between the dMMR tumors in the NICHE-1 (n = 21) and ACROBATICC (n = 43) cohorts differed, with older patients and fewer hereditary dMMRs in the 'real-life' ACROBATICC cohort. Higher expression of CD8+ in dMMR tumors compared with proficient mismatch repair (pMMR) tumors was statistically significant across both cohorts. At long-term follow-up, 2/43 patients with dMMR had died from recurrent colon cancer in the ACROBATICC cohort. Assuming a curative effect of neoadjuvant immunotherapy in addition to surgery in dMMR tumors, the NNT would be >20 patients for any additional survivor.
In unselected patients with colon cancer having dMMR, recurrence risk is very low after surgery. Assuming a curative effect of neoadjuvant immunotherapy beyond surgery alone, the NNT would be at least 20 patients to prevent one cancer death over surgery alone.
针对错配修复缺陷（dMMR）的可手术结肠癌新辅助免疫治疗试验报告称，手术标本的病理缓解率很高，但长期生存率尚不清楚。目前尚未在结肠癌中研究新辅助免疫治疗作为一种独立疗法且不进行后续根治性手术的情况。
本研究的目的是模拟试验数据与术后真实世界患者的预后情况。
我们对前瞻性试验数据（NICHE-1）与一项针对可手术结肠癌及微卫星不稳定性（MSI）状态患者的前瞻性、基于人群的转化队列研究（ACROBATICC）进行了比较建模研究。针对免疫细胞浸润、分期、MSI以及患者人口统计学特征，就不良事件、报告的肿瘤学结局以及预防复发所需的治疗人数（NNT）建模进行了比较。
NICHE-1队列（n = 21）和ACROBATICC队列（n = 43）中dMMR肿瘤患者的特征存在差异，“现实生活”中的ACROBATICC队列中患者年龄较大，遗传性dMMR患者较少。在两个队列中，与错配修复功能正常（pMMR）肿瘤相比，dMMR肿瘤中CD8+的表达更高，差异具有统计学意义。在长期随访中，ACROBATICC队列中有2/43例dMMR患者死于复发性结肠癌。假设新辅助免疫治疗对dMMR肿瘤除手术外还有治愈效果，那么每多挽救一名幸存者所需的治疗人数将超过20例患者。
在未经过选择的dMMR结肠癌患者中，术后复发风险非常低。假设新辅助免疫治疗除单纯手术外还有治愈效果，那么预防一例仅通过手术无法避免的癌症死亡至少需要20例患者接受治疗。
