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BACKGROUND
Multimodal treatment, including systemic treatment and surgery, improved the prognosis of peritoneal metastasis (PM). Despite all efforts, recurrence rates remain high, and only little data is available about clinical behavior or molecular patterns of PM in comparison to hematogenous metastasis. Here, we aimed to analyze recurrence patterns after multimodal treatment for PM from colorectal cancer.

METHODS
Patients with colorectal PM undergoing multimodal treatment including systemic chemotherapy and cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) between 2005-2017 at four centers were analyzed retrospectively.

RESULTS
A total of 505 patients undergoing CRS/HIPEC were analyzed. 82.1% of patients received preoperative chemotherapy. Median peritoneal cancer index (PCI) was 6 (IQR = 3-11). Median disease-free and overall survival was 12 months (95% confidence interval [CI] = 11 to 14 months) and 51 months (95% CI = 43 to 62 months) respectively. Disease recurred in 361 (71.5%) patients, presenting as isolated peritoneal recurrence in 24.6%, isolated hematogenous recurrence in 28.3%, and mixed recurrence in 13.9% of patients. Recurrence to the peritoneum was associated with an impaired time from recurrence to death of 21 months (95% CI = 18 to 31 months) for isolated peritoneal, and 22 months (95% CI = 16 to 30 months) for mixed recurrence, compared to 43 months (95% CI = 31 to > 121 months) for hematogenous recurrence (hazard ratio [HR] = 1.79, 95% CI = 1.27 to 2.53, p = .001 and HR = 2.44, 95% CI = 1.61 to 3.79, p < .001). On multiple logistic regression analysis, RAS mutational status (OR = 2.42, 95% CI = 1.11 to 5.47, p = .03) and positive nodal stage of the primary (OR = 3.88, 95% CI = 1.40 to 11.86, p = .01) were identified as predictive factors for peritoneal recurrence.

CONCLUSIONS
This study highlights the heterogeneity of peritoneal metastasis in patients with colorectal cancer. Recurrent peritoneal metastasis after radical treatment represents a more aggressive subset of metastatic colorectal cancer.