Perioperative chemotherapy in colorectal cancer with peritoneal metastases: A global propensity score matched study

Abstract

Background: There is a paucity of studies evaluating perioperative systemic chemotherapy in conjunction with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colorectal cancer peritoneal metastases (CRCPM). The aim was to evaluate neoadjuvant and/or adjuvant systemic therapy in CRCPM.

Methods: Patients with CRCPM from 39 treatment centres globally from January 1, 1991, to December 31, 2018, who underwent CRS+HIPEC were identified and stratified according to neoadjuvant/adjuvant use. Crude data analysis, propensity score matching (PSM) and Cox-proportional hazard modelling was performed.

Findings: Of 2093 patients, 1613 were included in neoadjuvant crude evaluation with 708 in the PSM cohort (354 patients/arm). In the adjuvant evaluation, 1176 patients were included in the crude cohort with 778 in the PSM cohort (389 patients/arm). The median overall survival (OS) in the PSM cohort receiving no neoadjuvant vs neoadjuvant therapy was 37.0 months (95% CI: 32.6-42.7) vs 34.7 months (95% CI: 31.2-38.8, HR 1.08 95% CI: 0.88-1.32, p = 0.46). The median OS in the PSM cohort receiving no adjuvant therapy vs adjuvant therapy was 37.0 months (95% CI: 32.9-41.8) vs 45.7 months (95% CI: 38.8-56.2, HR 0.79 95% CI: 0.64-0.97, p = 0.022). Recurrence-free survival did not differ in the neoadjuvant evaluation but differed in the adjuvant evaluation - HR 1.04 (95% CI: 0.87-1.25, p = 0.66) and 0.83 (95% CI: 0.70-0.98, p = 0.03), respectively. Multivariable Cox-proportional hazard modelling in the crude cohorts showed hazard ratio 1.08 (95% CI: 0.92-1.26, p = 0.37) for administering neoadjuvant therapy and 0.86 (95% CI: 0.72-1.03, p = 0.095) for administering adjuvant therapy.

Interpretation: Neoadjuvant therapy did not confer a benefit to patients undergoing CRS+HIPEC for CRCPM, whereas adjuvant therapy was associated with a benefit in this retrospective setting.

Funding: None.

Keywords: Adjuvant chemotherapy; Colorectal cancer; Cytoreductive surgery; Hyperthermic intraperitoneal chemotherapy; Neoadjuvant chemotherapy; Peritoneal metastases.

Fig. 1

Flowchart of patient data selection & analysis.

Fig. 2

Overall survival comparison between neoadjuvant therapy vs no neoadjuvant therapy in the propensity score matched group (n = 700), missing data on censoring variable or date of death (n = 8). Hazard ratio 1.08 (95% CI: 0.88–1.32), p-value 0.46. Median OS 34.7 months in the neoadjuvant group (95% CI: 31.2–38.8) vs 37.0 months in the no neoadjuvant group (95% CI: 32.6–42.7), log rank p-value 0.46.

Fig. 3

Overall survival comparison between adjuvant therapy vs no adjuvant therapy in the propensity score matched group (n = 771), missing data on censoring or date of death (n = 7). Hazard ratio 0.79 (95% CI: 0.64–0.97), p-value 0.022. Median OS 45.7 months in the adjuvant group (95% CI: 38.8–56.2) vs 37.0 months in the no adjuvant group (95% CI: 32.9–41.8), log rank p-value 0.022.

Fig. 4

Recurrence-free survival comparison between neoadjuvant therapy vs no neoadjuvant therapy in the propensity score matched group (n = 625), missing data on recurrences (n = 83). Hazard ratio 1.04 (95% CI: 0.87–1.25), p-value 0.66. Median OS 12.3 months in the neoadjuvant group (95% CI: 10.9–13.6) vs 12.6 months in the no neoadjuvant group (95% CI: 11.2–14.1), log rank p-value 0.66.

Fig. 5

Recurrence-free survival comparison between adjuvant therapy vs no adjuvant therapy in the propensity score matched group (n = 764), missing data on recurrences (n = 14). Hazard ratio 0.83 (95% CI: 0.70–0.98), p-value 0.030. Median RFS 12.7 months in the adjuvant group (95% CI: 11.6–14.7) vs 11.1 months in the no adjuvant group (95% CI: 10.2–12.5), log rank p-value 0.030.