# Tumoral and circulating genomic landscape inform survival differences in colorectal carcinomatosis

## TL;DR

The study shows that the genetic makeup of colorectal cancer that spreads to the peritoneum differs from liver metastases, affecting survival and treatment response.

## Contribution

The study identifies distinct mutational profiles and prognostic differences between colorectal peritoneal and liver metastases using ctDNA and tumor data.

## Key findings

- Patients with colorectal peritoneal metastases (CPM) had lower ctDNA positivity rates compared to those with isolated CPM.
- Mutations in BRAF and KRAS in ctDNA were linked to worse survival in CPM patients.
- Survival outcomes varied by metastatic site, highlighting the need for site-specific genomic profiling.

## Abstract

•The mutational profile and prognostic value of CPM are distinct from CLM.•Rates of ctDNA positivity were lower in patients with isolated CPM.•Improved survival was noted in CPM patients treated with FOLFIRI and Bevacizumab.

The mutational profile and prognostic value of CPM are distinct from CLM.

Rates of ctDNA positivity were lower in patients with isolated CPM.

Improved survival was noted in CPM patients treated with FOLFIRI and Bevacizumab.

Colorectal peritoneal metastases (CPM) are the third most common site of metastatic spread of colorectal cancer and are associated with worse survival than other sites of metastatic disease. In recent years tumoral circulating tumoral DNA (ctDNA) mutational status has been increasingly utilized in clinical decision making for metastatic colorectal cancer patients despite its utility in CPM being poorly understood. Here we describe standard of care performed mutational profiles and associated outcomes for unresectable CPM patients, with a contextual comparison to 160 unresected colorectal liver metastases (CLM) patients. Of 508 patients, 288 (57 %) had CPM alone and 220 (43 %) had CPM with extraperitoneal metastases. Patients with synchronous CPM and CLM had worse overall survival (HR 1.67 [95 %CI 1.26–2.22]). Mutations in ctDNA were noted in 110/145 (75.9 %) of CPM patients, with mutations in KRAS or PIK3CA ctDNA being associated with worse survival. Importantly, the association between tumoral mutational profile and survival differed by site of metastatic disease. The prognostic significance of specific mutations, particularly BRAF and KRAS, differs between patients with CPM and CLM, and supports the distinct biology of these metastatic sites and the importance of tissue and circulating genomic profiling to risk-stratify these patients according to site of metastasis.