Locally advanced colon cancer and peritoneal metastases From biological pathway to treatment strategies

Patients with locally advanced (T4) colon cancer constitute a challenging patient group, with R0 resection rates of only 90% and surgical complications in up to 35%. Potentially, the prone pT4 patient would benefit from laparoscopic surgery, with R0 resection rates comparable to after open surgery (96%), lower risk of postoperative complications (23% vs. 35%), and improved survival related to the increased proportion of patients receiving adjuvant chemotherapy. T4 colon cancer patients have a substantial risk at peritoneal metastases (PM) and adjuvant HIPEC was proposed as new strategy to prevent PM. In contrast to promising results of small cohort series, in the COLOPEC RCT, adjuvant HIPEC was not superior based on 18-months PM free survival compared to systemic chemotherapy alone (81% vs. 76%). Furthermore, surgical exploration 5-8 weeks after tumour resection preceding adjuvant HIPEC already revealed PM in 9 patients (10%). In order to identify patients at high-risk of PM, a mouse model was created, showing variation in the extent of PM amongst human CRC cell lines, with KRAS and BRAF mutations tending towards higher PCI scores. Lastly, we showed that the pathological diagnosis pT4 (and the associated risk of PM) is not as straightforward as commonly thought. In conclusion, no definite solution is given to the poor outcomes of T4 colon cancer. Growing insights in the biological formation of PM will potentially give rise to more effective (targeted) oncological agents. Together with better high-risk patient selection and improved surgical quality, this might in the future lead to improved adjuvant treatment.