Risk of metachronous peritoneal metastases in patients with pT4a versus pT4b colon cancer: An international multicentre cohort study

Abstract

Introduction: With evolving treatment strategies aiming at prevention or early detection of metachronous peritoneal metastases (PM), identification of high-risk colon cancer patients becomes increasingly important. This study aimed to evaluate differences between pT4a (peritoneal penetration) and pT4b (invasion of other organs/structures) subcategories regarding risk of PM and other oncological outcomes. Materials and methods: From eight databases deriving from four countries, patients who underwent curative intent treatment for pT4N0-2M0 primary colon cancer were included. Primary outcome was the 5-year metachronous PM rate assessed by Kaplan-Meier analysis. Independent predictors for metachronous PM were identified by Cox regression analysis. Secondary endpoints included 5-year local and distant recurrence rates, and 5-year disease free and overall survival (DFS, OS). Results: In total, 665 patients with pT4a and 187 patients with pT4b colon cancer were included. Median follow-up was 38 months (IQR 23e60). Five-year PM rate was 24.7% and 12.2% for pT4a and pT4b categories, respectively (p ¼ 0.005). Independent predictors for metachronous PM were female sex, rightsided colon cancer, peritumoral abscess, pT4a, pN2, R1 resection, signet ring cell histology and postoperative surgical site infections. Five-year local recurrence rate was 14% in both pT4a and pT4b cancer (p ¼ 0.138). Corresponding five-year distant metastases rates were 35% and 28% (p ¼ 0.138). Five-year DFS and OS were 54% vs. 62% (p ¼ 0.095) and 63% vs. 68% (p ¼ 0.148) for pT4a vs. pT4b categories, respectively. Conclusion: Patients with pT4a colon cancer have a higher risk of metachronous PM than pT4b patients. This observation has important implications for early detection and future adjuvant treatment strategies.

Risk factors for metachronous peritoneal carcinomatosis after radical resection for patients with nonmetastatic pT3‐4 colon cancer

“…Compared with T3 tumors, T4 tumors had a higher proportion of mPC; T4 tumors were regarded as "low risk PC" in a recent study, 15 and the risk of recurrent PC in patients with T4 tumors was only lower than that in patients with synchronous peritoneal or ovarian metastasis at the initial radical surgery. Several studies 17,21 have found that T4a stage cancer had much higher risk for PC after radical colon cancer resection compared with T3 and T4b stage cancer, but we did not find this in our present study (pT4b vs. pT4a, HR = 0.704, p = 0.343). However, the incidence of mPC in T4a was slightly higher in this cohort, the small number of T4 patients may be the reason for the lack of statistical difference.…”

“…Patients with an advanced T stage tumor were found to be at increased risk for developing mPC, which has been demonstrated previously. [11][12][13][14][15][16][17][18][19][20][21] In this study, the incidence of mPC of T3, T4a, and T4b was 6.3%, 25.0%, and 19.1%, respectively. Compared with T3 tumors, T4 tumors had a higher proportion of mPC; T4 tumors were regarded as "low risk PC" in a recent study, 15 and the risk of recurrent PC in patients with T4 tumors was only lower than that in patients with synchronous peritoneal or ovarian metastasis at the initial radical surgery.…”

“…To investigate the association between adjuvant chemotherapy and mPC further, we conducted a 1:1 propensity score matching (PSM) procedure to balance intergroup baseline characteristics and minimize confounding effects, and Cox regression analysis after PSM showed that adjuvant chemotherapy did not increase the risk of mPC (p = 0.169) (Supporting Information: Table S4), which was consistent with previous studies. 13,14,19,21,26 One recently published retrospective study pointed out that mutations on KRAS, NRAS, and BRAF as well as microsatellite instability may affect the development of mPC, but due to a lack of statistical analysis, the influence of tumor molecular markers on mPC was not clear. This study included the KRAS, NRAS, BRAF, and MMR status into analysis for the first time to clarify their influence on mPC.…”

“…2,6,7 Most studies suggest that the incidence of tumor-positive cytology in the abdominal cavity is significantly correlated with more advanced T stage of disease, 6,[8][9][10] and pT4 has been found to be markedly correlated with a higher risk of mPC. [11][12][13][14][15][16][17][18][19][20][21] However, identification between deep T3 and T4 tumors remains controversial. 22,23 Panarelli et al 24 recently showed that peritoneal cytology was positive in 19% of T3 and 55% of T4 tumors.…”

“…Generally, peritoneal carcinomatosis (PC) is caused by cancerous tumor emboli spreading or seeding in the peritoneum, 2,4,5 and patients with tumor‐positive cytology in the abdominal cavity are at significantly greater risk of mPC 2,6,7 . Most studies suggest that the incidence of tumor‐positive cytology in the abdominal cavity is significantly correlated with more advanced T stage of disease, 6,8–10 and pT4 has been found to be markedly correlated with a higher risk of mPC 11–21 . However, identification between deep T3 and T4 tumors remains controversial 22,23 .…”