Precision Medicine in Colorectal Cancer: Revolutionizing Cytoreductive Surgery and HIPEC

Colorectal cancer treatment is witnessing a paradigm shift, driven by the transformative power of precision medicine, with major guidelines increasingly recognizing the role of biomarker-driven decision-making across the care continuum.

Building on surgical strategy, molecular profiling contributes to operative planning by informing patient selection, expected completeness of cytoreduction, and perioperative systemic therapy choices. Precision medicine informs colorectal cancer care by tailoring systemic therapies to individual tumor biology and by refining prognostication; its role in selecting intraperitoneal chemotherapy agents for procedures like HIPEC is still emerging and not yet standardized. In peritoneal metastases, this approach shows promise for improving patient selection and aligning treatments to risk profiles, addressing the limitations of a one-size-fits-all methodology. The integration of molecular profiling is being investigated for its potential impact on selecting chemotherapy strategies around CRS and HIPEC, but this is not yet reflected in consensus guidelines, as explored in recent translational analyses of biomarker-informed strategies.

Effective patient selection for CRS and HIPEC is crucial, typically incorporating PCI, performance status (e.g., ECOG), and the absence of unresectable extraperitoneal disease alongside tumor biology and disease extent. Successful outcomes heavily depend on having a lower Peritoneal Cancer Index (PCI) and the potential to achieve complete cytoreduction, ideally CC-0 or CC-1. Moreover, favorable tumor biology plays a crucial role—for example, RAS/BRAF wild-type status and absence of adverse histology such as signet-ring features—helping ensure candidates are selected for their best chance to benefit.

Evidence for HIPEC in colorectal cancer is mixed—for instance, oxaliplatin-based HIPEC did not improve overall survival in the PRODIGE 7 trial—yet research continues to explore where and how CRS and intraperitoneal therapies might add value. Enhanced pharmacological and delivery approaches are being investigated to better address micrometastatic disease—for example, techniques such as pressurized intraperitoneal aerosol chemotherapy (PIPAC)—but their definitive impact in colorectal peritoneal metastases remains to be established. Examples of ongoing innovation include enhanced intraoperative imaging, standardized perioperative pathways, and refined anesthetic and critical-care protocols—developments that aim to improve safety and consistency without presuming specific survival benefits.

Key Takeaways:

• Precision medicine primarily guides systemic therapy and risk stratification; its role in intraperitoneal agent selection for HIPEC is investigational.
• Patient selection frameworks typically include PCI thresholds, ECOG performance status, and absence of unresectable extraperitoneal disease, with goals of CC-0/CC-1 cytoreduction.
• HIPEC evidence is mixed; ongoing trials and translational work aim to clarify where CRS plus intraperitoneal therapies may provide benefit.
• Innovation is active but should be framed cautiously, with examples such as improved intraoperative imaging, perioperative pathways, and PIPAC under evaluation.