RAS Mutation Decreases Overall Survival After Optimal Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy of Colorectal Peritoneal Metastasis: A Modification Proposal of the Peritoneal Surface Disease Severity Score

Ann Surg Oncol. 2019 Aug;26(8):2595-2604. doi: 10.1245/s10434-019-07378-9. Epub 2019 May 20.


Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are currently the most accepted treatment for peritoneal metastases from colorectal cancer. Restrictive selection criteria are essential to obtain the best survival benefits for this complex procedure. The most widespread score for patient selection, the peritoneal surface disease severity score (PSDSS), does not include current biological factors that are known to influence on prognosis. We investigated the impact of including RAS mutational status in the selection criteria for these patients.

Methods: We studied the risk factors for survival by multivariate analysis using a prospective database of consecutive patients with carcinomatosis from colorectal origin treated by CRS and HIPEC in our unit from 2009 to 2017. The risk factors obtained were validated in a multicentre, international cohort, including a total of 520 patients from 15 different reference units.

Results: A total of 77 patients were selected for local análisis. Only RAS mutational status (HR: 2.024; p = 0.045) and PSDSS stage (HR: 2.90; p = 0.009) were shown to be independent factors for overall survival. Early PSDSS stages I and II associated to RAS mutations impaired their overall survival with no significant differences with PSDSS stage III overall survival (p > 0.05). These results were supported by the international multicentre validation.

Conclusions: By including RAS mutational status, we propose an updated RAS-PSDSS score that outperforms PSDSS alone providing a quick and feasible preoperative assessment of the expected overall survival for patients with carcinomatosis from colorectal origin undergone to CRS + HIPEC.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemotherapy, Cancer, Regional Perfusion / mortality*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy
  • Combined Modality Therapy
  • Cytoreduction Surgical Procedures / mortality*
  • Female
  • Follow-Up Studies
  • Humans
  • Hyperthermia, Induced / mortality*
  • Male
  • Middle Aged
  • Mutation*
  • Peritoneal Neoplasms / genetics
  • Peritoneal Neoplasms / mortality*
  • Peritoneal Neoplasms / secondary
  • Peritoneal Neoplasms / therapy
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • ras Proteins / genetics*


  • ras Proteins