Expanding the horizons of cytoreductive surgery-hyperthermic intraperitoneal chemotherapy and liver resection for colorectal peritoneal and liver metastases

The prognosis of colorectal cancer (CRC) metastases largely depends on their resectability. When metastases are confined to a single organ (e.g., liver-only or lung-only metastases), the prognosis tends to be more favorable. Hepatectomy is well established as the standard treatment for colorectal liver metastases (CLM), with recent studies reporting a 5-year survival rate of 62.4% in patients undergoing liver resection (1). Similarly, metastasectomy for lung metastases from CRC may achieve 5-year survival rates of approximately 50% (2).

Historically, difficulties in diagnosis and curative resection have contributed to poor survival outcomes in peritoneal metastases from CRC (PM-CRC). The survival rate of peritoneal-only metastases is significantly worse than that of other single-organ metastases (3). Recent advancements in cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have demonstrated improved survival in selected PM-CRC patients with a reported 5-year survival rate of 30–50% (4-6). However, due to the high morbidity associated with CRS and HIPEC, careful patient selection is crucial. Moreover, the presence of synchronous liver, lung, or other distant metastases has been considered a relative contraindication for CRS-HIPEC (7). Nevertheless, in clinical practice, 8% of patients with CRC present with synchronous peritoneal and liver metastases (8), creating a significant dilemma regarding whether resection should be performed despite technical feasibility.

The recent study by Dagenborg et al. provides valuable insight into this issue. Their study assessed the feasibility and outcomes of CRS-HIPEC combined with liver resection in patients with colorectal peritoneal and liver metastases. The median overall survival (OS) of 57 patients was 48 months, demonstrating the potential benefit of this approach. Furthermore, no significant survival difference was found based on the timing of liver resection (before, during, or after CRS-HIPEC). These findings suggest that aggressive surgical management may be viable for carefully selected patients, challenging the conventional contraindication of CRS-HIPEC in cases with synchronous liver metastases. Importantly, 90-day mortality was zero in this study, emphasizing the safety of CRS-HIPEC combined with liver resection when applied to appropriately selected patients (9).

These findings contradict the traditional notion that liver metastases preclude CRS-HIPEC and instead support a multimodal treatment strategy. However, the criteria for liver metastasis resectability were not clearly defined in this study. Most liver resections involved partial hepatectomy within two subsegments, and the majority of patients had two or fewer liver metastases. Future studies should establish clearer resectability criteria to enhance their applicability in clinical practice.

There are some limitations to this study. The relatively small sample size (57 patients) restricts the generalizability of the findings, and validation in larger, multi-institutional cohorts is necessary. Furthermore, the absence of a control group receiving systemic therapy alone makes it difficult to establish a causal relationship between CRS-HIPEC with liver resection and improved survival.

Furthermore, precise preoperative assessment of disease burden is crucial. The peritoneal cancer index (PCI) is the strongest prognostic factor for CRS-HIPEC candidates, and accurate PCI assessment is essential (10). Recent studies suggest that diagnostic laparoscopy or magnetic resonance imaging (MRI) assessment may improve patient selection (11,12). Integrating these techniques into standard preoperative evaluation protocols could enhance treatment outcomes and avoid unnecessary surgery.

Additionally, the role of molecular markers in patient selection remains an important research focus. Studies suggest that BRAF mutations are associated with poor prognosis in PM-CRC, raising the question of whether CRS-HIPEC should be offered to BRAF-mutated patients (13). Future research should incorporate molecular profiling to optimize treatment selection.

Future considerations

• Where should we set the selection criteria for considering CRS-HIPEC and liver resection in patients with colorectal peritoneal and liver metastases? What is the optimal PCI cutoff, and how many liver metastases or what extent of tumor burden in the liver can be considered acceptable? While patients with PCI between 15 and 20 or with ≤2 liver metastases have shown favorable outcomes in selected series, standardized thresholds for both peritoneal and hepatic tumor burden remain to be established and require further investigation.
• Is HIPEC always necessary? Would CRS alone be sufficient for certain subgroups of PM-CRC patients with limited liver metastases?
• How should metachronous liver metastases (MLM) following CRS-HIPEC be managed? Severe adhesions, particularly following CRS-HIPEC with peritonectomy of the right subdiaphragmatic region and manipulation of the lesser omentum and hepatic hilum, can make subsequent hepatectomy technically challenging due to dense adhesions between the liver and diaphragm, as well as around the hepatic hilum. Nevertheless, in the absence of peritoneal recurrence, resection may be considered (14). Further studies are needed to refine selection criteria and optimize outcomes.
• How can emerging technologies improve patient selection and prognosis? The role of robot-assisted CRS, pressurized intraperitoneal aerosol chemotherapy (PIPAC), and circulating tumor DNA (ctDNA)-guided surveillance warrants further exploration.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, HepatoBiliary Surgery and Nutrition. The article has undergone external peer review.

Peer Review File: Available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-2025-189/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-2025-189/coif). N.K. serves as an unpaid editorial board member of HepatoBiliary Surgery and Nutrition. The other author has no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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