Objective  To investigate the relationship between preoperative serum CA19-9 levels and pathological grades in pseudomyxoma peritonei (PMP) and evaluate its impact on overall survival.

Methods  A retrospective analysis was conducted on clinical data from 321 patients with PMP who underwent initial cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) by our team between October 2004 and October 2024. Receiver operating characteristic curve analysis was used to assess the discriminative value of CA19-9 for the pathological grade. Kaplan–Meier analysis was conducted to evaluate the impact of preoperative CA19-9 on overall survival.

Results  Among the 321 patients included in this study, 148 (46.1%) had increased preoperative CA19-9 levels, which were associated with pathological grades. When preoperative CA19-9 >693.3 U/mL, the pathological grade was more likely to be high-grade peritoneal mucinous carcinoma with signet ring cells (area under the curve: 0.67, 95% confidence interval: 0.54–0.80, P= 0.021). Elevated preoperative CA19-9 was an independent risk factor for overall survival in patients with PMP (mOS was 53.62 m vs. not reached in the elevated group vs. normal group, respectively, P<0.001).

Conclusions Preoperative serum CA19-9 levels were associated with pathological grades in patients with PMP undergoing initial CRS+HIPEC, with an independent negative impact on overall survival.