Integrating Peritoneal Histological Growth Patterns Into Preoperative Decision-Making for Colorectal Peritoneal Metastses

Colorectal cancer (CRC) remains the third most commonly diagnosed malignancy worldwide and the second leading cause of cancer-related death, with approximately 15% of patients presenting with synchronous liver metastases (LM) and 7% with peritoneal metastases (PM) at diagnosis. Despite curative-intent resection of the primary tumor, 16-20% of patients subsequently develop metachronous LM and up to 19% develop PM within three years \[1-5\]. Surgery remains the only potentially curative treatment for patients with colorectal peritoneal metastases (CRPM), offering long-term (\>10years) disease-free survival (DFS) in a subset of highly selected patients \[6,7\]. However, selecting candidates for cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC) remains challenging and requires balancing the potential oncologic benefit of complete cytoreduction against perioperative risks and postoperative morbidity \[6-8\]. Consequently, strong prognostic markers-clinical, biological, or genetic-are crucial to refine surgical decision-making. Currently, the two most consistent clinical determinants of outcome are the extent of disease (Peritoneal Cancer Index, PCI) and the completeness of cytoreduction (CC-score) \[6-8\]. Over the last decade, surgical selection has become more restrictive (e.g., PCI threshold moving from 25 to 17), and molecular profiles such as BRAF mutations have been associated with poor outcomes, potentially guiding against aggressive surgery in selected cases \[8,9\]. Yet, these markers are insufficient to fully capture inter-patient heterogeneity and do not reliably individualize surgical benefit \[8,9\]. In colorectal liver metastases (CRLM), the histological growth pattern (HGP) at the tumor-liver interface has emerged as a robust prognostic biomarker, with the desmoplastic HGP (d-HGP) associated with superior survival compared with replacement or pushing patterns \[10,11\]. International consensus guidelines have standardized H