Department of Surgery, Amsterdam UMC location University of Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands.
Treatment and Quality of Life, Cancer Center Amsterdam, Amsterdam, the Netherlands.
Mod Pathol. 2022 Dec;35(12):1991-2001. doi: 10.1038/s41379-022-01154-z. Epub 2022 Sep 19.
Substantial variability exists in what pathologists consider as pT4a in colorectal cancer when tumor cells are within 1 mm of the free peritoneal surface. This study aimed to determine if the measured sub-millimeter distance between tumor cells and the free peritoneal surface would offer an objective means of stratifying patients according to the risk of developing peritoneal metastases. Histological slides of patients included in the COLOPEC trial, with resectable primary c/pT4N0-2M0 colon cancer, were centrally reassessed. Specific tumor morphological variables were collected, including distance from tumor to free peritoneal surface, measured in micrometers (µm). The primary outcome, 3-year peritoneal metastasis rate, was compared between four groups of patients stratified for relation of tumor cells to the peritoneum: 1) Full peritoneal penetration with tumor cells on the peritoneal surface, 2) 0-99 µm distance to the peritoneum, 3) 100-999 µm to the peritoneum, and 4) ≥1000 µm to the peritoneum, by using Kaplan-Meier analysis. In total, 189 cases were included in the present analysis. Cases with full peritoneal penetration (n = 89), 0-99 µm distance to the peritoneal surface (n = 34), 100-999 µm distance (n = 33), and ≥1000 µm distance (n = 33), showed significantly different 3-year peritoneal metastases rates of 25% vs 29% vs 6% vs 12%, respectively (Log Rank, p = 0.044). N-category did not influence the risk of peritoneal metastases in patients with a tumor distance beyond 100 µm, while only the N2 category seemed to result in an additive risk in patients with a distance of 0-99 µm. The findings of this study suggest that the measured shortest distance between tumor cells and the free peritoneal surface is useful as an objective means of stratifying patients according to the risk of developing peritoneal metastases. This simple measurement is practical and may help in providing a precise definition of pT4a. Trial registration: NCT02231086 (Clinicaltrials.gov).
在结直肠癌中，当肿瘤细胞距离游离腹膜表面 1 毫米以内时，病理学家对 pT4a 的定义存在很大差异。本研究旨在确定肿瘤细胞与游离腹膜表面之间的亚毫米测量距离是否可以提供一种客观的方法，根据发生腹膜转移的风险对患者进行分层。对 COLOPEC 试验中可切除原发性 c/pT4N0-2M0 结肠癌患者的组织学切片进行了中心重新评估。收集了包括肿瘤与游离腹膜表面的距离在内的特定肿瘤形态学变量，以微米 (µm) 为单位进行测量。主要结局为 3 年腹膜转移率，根据肿瘤细胞与腹膜的关系，将患者分为四组进行比较：1) 肿瘤细胞完全穿透腹膜并位于腹膜表面，2) 距离腹膜 0-99µm，3) 距离腹膜 100-999µm，4) 距离腹膜≥1000µm，采用 Kaplan-Meier 分析。共纳入本分析 189 例病例。完全穿透腹膜（n=89）、距离腹膜表面 0-99µm（n=34）、100-999µm（n=33）和≥1000µm（n=33）的病例，3 年腹膜转移率分别为 25%、29%、6%和 12%，差异有统计学意义（Log Rank，p=0.044）。在距离肿瘤 100µm 以上的患者中，N 分期并不影响腹膜转移的风险，而只有 N2 分期似乎会增加距离 0-99µm 的患者发生腹膜转移的风险。本研究结果表明，测量肿瘤细胞与游离腹膜表面之间的最短距离可作为一种客观的方法，根据发生腹膜转移的风险对患者进行分层。这种简单的测量方法实用，有助于对 pT4a 进行精确定义。试验注册：NCT02231086（Clinicaltrials.gov）。
