Abdominalcenter K, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark.
Department of Pathology, Copenhagen University Hospital - Rigshospital, Copenhagen, Denmark.
Ann Surg Oncol. 2024 Oct;31(10):6423-6431. doi: 10.1245/s10434-024-15595-0. Epub 2024 Jun 21.
There is mounting evidence that microscopically positive (R1) margins in patients with colorectal cancer (CRC) may represent a surrogate for aggressive cancer biology rather than technical failure during surgery. However, whether detectable biological differences exist between CRC with R0 and R1 margins is unknown. We sought to investigate whether mismatch repair (MMR) status differs between Stage III CRC with R0 or R1 margins.
Patients treated for Stage III CRC from January 1, 2016 to December 31, 2019 were identified by using the Danish Colorectal Cancer Group database. Patients were stratified according to MMR status (proficient [pMMR] vs. deficient [dMMR]) and margin status. Outcomes of interest included the R1 rate according to MMR and overall survival.
A total of 3636 patients were included, of whom 473 (13.0%) had dMMR colorectal cancers. Patients with dMMR cancers were more likely to be elderly, female, and have right-sided cancers. R1 margins were significantly more common in patients with dMMR cancers (20.5% vs. 15.2%, p < 0.001), with the greatest difference seen in the rate of R1 margins related to the primary tumour (8.9% vs. 4.7%) rather than to lymph node metastases (11.6% vs. 10.5%). This association was seen in both right- and left-sided cancers. On multivariable analyses, R1 margins, but not MMR status, were associated with poorer survival, alongside age, pN stage, perineural invasion, and extramural venous invasion.
In patients with Stage III CRC, dMMR status is associated with increased risks of R1 margins following potentially curative surgery, supporting the use of neoadjuvant immunotherapy in this patient group.
越来越多的证据表明，结直肠癌（CRC）患者的显微镜下阳性（R1）切缘可能代表侵袭性癌症生物学的替代指标，而不是手术过程中的技术失败。然而，R0 和 R1 切缘的 CRC 是否存在可检测的生物学差异尚不清楚。我们试图研究 R0 或 R1 切缘的 III 期 CRC 之间错配修复（MMR）状态是否存在差异。
通过丹麦结直肠癌组数据库确定了 2016 年 1 月 1 日至 2019 年 12 月 31 日期间接受 III 期 CRC 治疗的患者。根据 MMR 状态（ proficient [pMMR] 与 deficient [dMMR]）和切缘状态对患者进行分层。感兴趣的结局包括 MMR 状态下的 R1 率和总生存率。
共纳入 3636 例患者，其中 473 例（13.0%）为 dMMR 结直肠癌患者。dMMR 癌症患者更可能年龄较大、女性和右半结肠癌。dMMR 癌症患者的 R1 切缘更为常见（20.5%比 15.2%，p < 0.001），在原发性肿瘤相关 R1 切缘率（8.9%比 4.7%）方面差异最大，而非淋巴结转移（11.6%比 10.5%）。这种关联在右半和左半结肠癌中均存在。多变量分析显示，R1 切缘与 MMR 状态无关，与较差的生存相关，与年龄、pN 分期、神经周围侵犯和外膜静脉侵犯相关。
在 III 期 CRC 患者中，dMMR 状态与潜在治愈性手术后 R1 切缘的风险增加相关，支持在该患者组中使用新辅助免疫治疗。
