Colon cancer remains one of the most common malignancies worldwide, with significant challenges in treatment and recurrence. Among patients with locally advanced colon cancer, nearly 25% develop locoregional recurrence, including peritoneal metastases, which severely compromises prognosis. In a bid to improve outcomes, a recent meta-analysis by Hamm et al., published in the Annals of Oncology, explores the potential benefits of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) for these high-risk patients.
Understanding HIPEC
Hyperthermic intraperitoneal chemotherapy (HIPEC) involves the direct administration of heated chemotherapy into the abdominal cavity post-surgery. The heat enhances the effectiveness of the chemotherapeutic agents, aiming to eliminate residual microscopic cancer cells. This procedure has shown promise in treating various abdominal cancers, including peritoneal carcinomatosis, but its role in preventing recurrence in colon cancer has been under investigation.
The Meta-Analysis: A Comprehensive Review
Hamm et al.’s study aimed to identify specific subgroups of colon cancer patients who might benefit most from prophylactic HIPEC. A systematic literature search identified randomised controlled trials (RCTs) on the subject up to 1st August 2023. The meta-analysis focused on the primary endpoint of 3-year locoregional recurrence rate, with secondary endpoints being 3-year disease-free survival and overall survival.
Two RCTs, COLOPEC and HIPECT4, met the inclusion criteria, pooling data from a total of 386 patients. Among these, 189 patients received prophylactic HIPEC, while 197 served as controls. The median follow-up period was 36 months.
Key Findings
The modified intention-to-treat analysis revealed a noteworthy reduction in the 3-year locoregional recurrence rate for patients who underwent HIPEC. Specifically, the recurrence rate was 18% in the HIPEC group compared to 25% in the control group (Hazard Ratio [HR] 0.75, 95% Confidence Interval [CI] 0.47 – 1.22). While this reduction is promising, the HR confidence interval suggests variability and indicates the need for further research.
Predefined subgroup analyses provided more granular insights:
- Patients with Right-Sided Tumours: This subgroup showed a significant reduction in locoregional recurrence with HIPEC (HR 0.47; 95% CI 0.29 – 0.77). Right-sided colon cancers are often associated with a different molecular profile and worse prognosis compared to left-sided tumours, making this finding particularly significant.
- Patients with pN1 Stage: These patients, characterised by limited lymph node involvement, also benefited from HIPEC (HR 0.92; 95% CI 0.85 – 0.99). This suggests that even patients with relatively early nodal involvement can gain protective effects from the procedure.
- Patients with Right-Sided pT4 Tumours: Those with tumours invading nearby structures or organs (pT4 stage) saw the most significant reduction in recurrence rates (HR 0.47; 95% CI 0.29 – 0.77), highlighting HIPEC’s potential in cases of extensive local spread.
Disease-Free and Overall Survival
Despite the reductions in locoregional recurrence, the meta-analysis did not show significant differences in 3-year disease-free survival and overall survival between the HIPEC and control groups. This highlights the complexity of cancer progression and the multitude of factors influencing long-term outcomes.
Implications and Future Directions
The findings of Hamm et al. suggest that adding prophylactic HIPEC to surgical resection and adjuvant systemic chemotherapy could be beneficial, particularly for high-risk subgroups of colon cancer patients. However, the variability indicated by the confidence intervals and the lack of significant improvements in disease-free and overall survival highlight the need for further studies.
Future research should focus on refining patient selection criteria, optimising HIPEC protocols, and understanding the molecular underpinnings that contribute to different responses to treatment. Additionally, larger-scale RCTs with longer follow-up periods could provide more definitive answers regarding the role of prophylactic HIPEC in improving survival outcomes.
Conclusion
Prophylactic HIPEC shows promise in reducing locoregional recurrence rates in patients with locally advanced colon cancer, particularly those with right-sided tumours, pN1 stage, and right-sided pT4 tumours. While these findings are encouraging, further research is essential to fully establish the efficacy and survival benefits of this approach. For now, HIPEC represents a potential advancement in the multidisciplinary management of high-risk colon cancer patients, offering hope for improved prognoses in a challenging disease.
