# Clinical and Pathological Risk Factors for Peritoneal Metastases in a Surgical Series of T4 Colorectal Cancers

## TL;DR

The study identifies clinical and pathological factors that predict peritoneal metastases in T4 colorectal cancer patients, helping to better select candidates for early treatment.

## Contribution

The study provides new insights into risk factors for peritoneal metastases in T4 CRC patients, particularly the role of CEA and lymph node status.

## Key findings

- Synchronous peritoneal metastases prevalence was 20.7% in T4 CRC patients.
- Patients with negative lymph nodes and normal CEA had minimal risk of metachronous peritoneal metastases.
- Postoperative chemotherapy and positive resection margins were significantly associated with peritoneal metastases.

## Abstract

The interest in T4 colorectal cancer (CRC) has recently grown since different strategies based on the use of hyperthermic intraperitoneal chemotherapy (HIPEC) for the prevention or early treatment of peritoneal metastases have been clinically tested. However, the magnitude of the risk of peritoneal metastases in T4 CRC patients is not well defined. Analogously, the clinical/pathological factors that may help in identifying a subset of patients who deserve to be treated or not are still poorly understood. In our large surgical series, the prevalence of synchronous peritoneal metastases was 20.7%, and the 3-year cumulative incidence of metachronous peritoneal metastases was 21.5%. Negative lymph nodes and normal CEA-defined T4 tumours were at minimal risk for metachronous peritoneal dissemination. A potential implication of our observation is the possibility of more efficiently selecting higher-risk patients for the early detection and treatment of PM after curative resection, thus preventing overtreatment with an unfavourable harm/benefit ratio.

Background: T4 colorectal cancer (CRC) is associated with an increased risk of peritoneal metastases (PM), but it is currently not possible to accurately predict which patients with T4 CRC develop PM. We investigated the occurrence and risk factors for PM in these patients. Methods: A mono-institutional prospective database of 352 patients undergoing T4 primary CRC resection from 2012 to 2021 was reviewed. Clinico-pathological variables potentially associated with synchronous or metachronous PM were tested by univariate and multivariate analyses. Results: The prevalence of synchronous PM was 73/352 (20.7%) and was significantly associated with age (p = 0.037), primary site (p = 0.002), positive nodes (p = 0.005), elevated CA19.9 (p = 0.001), and non-intestinal histology (p = 0.001). After a median follow-up of 35.9 months (95% confidence interval [CI] = 29.5–44.9), metachronous CRC-PM occurred in 36/164 patients (22.0%) with available data, accounting for a three-year cumulative incidence of 21.5% (95% CI = 14.3–28.1). Metachronous CRC-PM occurred in 3/48 patients (6.2%) with negative nodes and normal CEA, as compared with 33/116 patients (28.4%) with positive nodes and/or elevated CEA (p < 0.001). Combined nodal and CEA status (hazard ratio [HR] = 1.27; 95% CI = 1.02–1.59; p = 0.033), postoperative chemotherapy (HR= 0.51; 95% CI = 0.33–0.77; p = 0.001), and positive resection margins (HR = 2.01; 95% CI = 1.20–3.39; p = 0.008) were significantly associated with PM. Conclusions: The peritoneum is a major site for treatment failure in T4 CRC. Patients with normal CEA and negative lymph nodes are associated with a significantly lower risk for metachronous CRC-PM. These findings may help in refining patient selection for integrated approaches aiming at the prevention or early treatment of CRC-PM, which are pending validation in prospective studies.