Limited clinical utility of mutation-based circulating tumor DNA detection in pseudomyxoma peritonei

Pseudomyxoma peritonei (PMP) is a rare abdominal cancer where curative treatment involves cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Postoperative surveillance relies on radiological imaging and blood tumor markers, which lack sensitivity and specificity. Circulating tumor DNA (ctDNA) analysis could offer a non-invasive alternative, but evidence in PMP is limited. Plasma samples from 95 PMP patients carrying KRAS and/or GNAS tumor mutations were analyzed using droplet digital PCR. Clinicopathological parameters and outcome were assessed, and disease-free survival (DFS) was analyzed using Cox regression. ctDNA was detected in 8 of 95 patients (8%), with low (median 0.1) mutated allele frequency with four positive cases at baseline, three at the time of recurrence, and one follow-up sample. Appendix tumor histology, high-grade peritoneal disease, and elevated baseline CA19-9 were independently associated with inferior DFS. Currently, mutation-based ctDNA detection cannot replace conventional postoperative surveillance for PMP patients.