Prognostic impact of ctDNA status and multi-site disease burden for patients with peritoneal metastases from appendiceal or colorectal cancer

Purpose: Circulating tumor DNA (ctDNA) is prognostic for patients with metastatic appendiceal and colorectal cancer (CRC), however, its impact on therapy considerations and surgical candidacy is unclear. Current randomized trials are exploring approaches to locoregional therapy for management of multi-site oligometastatic disease. We investigate the role of ctDNA-guided locoregional therapies in the management of peritoneal metastases (PM) with or without multi-site disease. Methods: The study cohort included high-grade appendiceal or CRC patients with single site (peritoneum) or multi-site metastases (peritoneum plus liver, lung, or distant lymph node involvement) who had curative intent surgical interventions for PM between 2023-2025. ctDNA testing was performed in the pre- and post-operative setting. Univariate and multivariate analysis of demographics, pathological, and ctDNA dynamics were performed. Overall survival (OS) was analyzed using Kaplan-Meier (KM) curves to evaluate prognostic impact of ctDNA status and presence of multi-site disease. Results: Of the 61 patients in the study, 67% (n=41) had CRC and 33% (n=20) had high-grade appendiceal cancer. Median postoperative follow up was 18 months with 82% of patients alive at last follow up. Prior to surgery, 33% (n=17) of patients were ctDNA positive with 13% clearing their ctDNA postoperatively initially. However, none of these patients maintained durable negative ctDNA as all converted back to ctDNA positive within 6 months. Of those with negative ctDNA preoperatively, 32% converted to ctDNA positive postoperatively - including 91% converting to positive within 1 year. Patients with ctDNA negative status preoperatively had KM-estimated 2-year OS of 91.2%. History of multi-site disease was present in 39% (n=24) of patients at time of surgery including 50% (n=12) with active multi-site disease and 50% (n=12) with previously treated disease. KM-estimated 2-year OS was excellent for ctDNA negative patients regardless of multi-site disease involvement (2-year OS = 83.3%) or peritoneal-only metastases (2-year OS = 95.6%). Conclusion: This study analyzed the prognostic impact of ctDNA status and multi-site disease for patients with PM from CRC or appendiceal cancer who underwent locoregional therapy. ctDNA appears to be prognostic in patients undergoing curative intent surgical resection for peritoneal metastases. Furthermore, patients with multi-site disease who have negative ctDNA and undergo surgery for peritoneal metastases appear to have survival comparable to patients with peritoneal only metastases. With variable approaches and conflicting guidelines for the management of patients with PM and oligometastatic disease, ctDNA could augment treatment selection, surgical eligibility, and clinical trial enrollment.