Colorectal Peritoneal Metastasis Research Gaps

High-Priority Areas

The European Society for Medical Oncology (ESMO) 2023 guidelines state that other HIPEC regimens using mitomycin and different procedures are under investigation, making this a priority area where surgical research could definitively answer whether any form of HIPEC improves mortality and quality of life 1, 2
The American Society of Clinical Oncology (ASCO) 2023 guidelines emphasize that complete cytoreduction is the most critical prognostic factor, but pre-operative prediction of achievability remains imprecise 4, 5
The National Institute for Health and Care Excellence (NICE) guidelines emphasize that shared decision-making must include quality of life impact, but current data are insufficient to inform these discussions 5, 6
Research should focus on randomized trials comparing different systemic chemotherapy timing strategies (neoadjuvant vs. adjuvant vs. perioperative) specifically in patients undergoing CRS for peritoneal metastases, with mortality and quality of life as primary endpoints 4, 5
The ASCO and ESMO guidelines mandate treatment at specialized centers, but specific criteria are lacking 4, 5, 6

Post-operative systemic chemotherapy is associated with improved overall survival (HR 0.81, p<0.00001), but the optimal timing, duration, and specific regimens remain undefined 4, 5
The proportion of patients with initially unresectable peritoneal metastases who can be converted to resectable disease with modern systemic therapy is unknown, and research should define response rates to triplet chemotherapy (FOLFOXIRI) plus biologics in peritoneal-only disease 1, 2, 9
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) and sequential postoperative intraperitoneal chemotherapy (SPIC) represent emerging modalities with limited evidence in colorectal peritoneal metastases, and research should compare PIPAC versus systemic chemotherapy alone in unresectable disease 7, 8

Only 15% of patients remain progression-free at 5 years after CRS, indicating that current selection criteria fail to identify the minority who truly benefit, and critical research areas include molecular markers beyond RAS/BRAF that predict complete cytoreduction feasibility 4, 5, 6
Genomic signatures that identify patients likely to achieve durable disease control, and validation of PCI thresholds (current cutoff <20) across different populations are needed 4, 5, 6

Treatment-related mortality ranges from 0.9-8%, and grade 3+ complications occur in 15-24% of patients, but comprehensive quality of life data are lacking, and research priorities include patient-reported outcomes comparing CRS alone versus CRS + systemic chemotherapy 5, 6
Long-term bowel function, nutritional status, and return to baseline activities should be evaluated, and decision aids incorporating realistic survival expectations (15% progression-free at 5 years) are needed 5, 6

The PRODIGE 7 trial achieved 91% complete cytoreduction rates due to center expertise, but minimum volume and technical standards for CRS centers are undefined, and research should establish minimum annual case volumes required to maintain acceptable morbidity/mortality 5, 6
Standardized surgical technique protocols for peritoneal stripping, and training curricula and credentialing requirements for surgeons performing CRS are needed 6