Locally advanced colon cancer and peritoneal metastases: New paradigms in treatment and classification

This thesis explores locoregional recurrence (LRCC) and peritoneal metastases in colon cancer, focusing on incidence, risk factors, prognosis, and treatment strategies, including Hyperthermic Intraperitoneal Chemotherapy (HIPEC), as well as improvements in classification and surgical techniques. Part I addresses LRCC and the development of peritoneal metastases. Chapter 1 defines LRCC as a distinct clinical entity and reviews its incidence and treatment outcomes. Recent studies report an incidence of approximately 5%, lower than earlier estimates. Surgical treatment in selected patients offers meaningful outcomes, with median survival around 30–33 months. In the authors’ institutional cohort (17 patients), median disease-free survival was 36 months and 3-year overall survival reached 65%. These findings suggest that carefully selected patients can benefit from curative-intent surgery, achieving prolonged disease control. Chapter 2 investigates synchronous and metachronous peritoneal metastases in a nationwide cohort of over 3,000 patients with left-sided obstructive colon cancer. Synchronous metastases occurred in 5% of patients, while the 3-year cumulative incidence of metachronous metastases was 9.9%. Independent risk factors included advanced tumor stage (pT4) and extensive nodal involvement (pN2). Prognosis was significantly worse for patients with peritoneal metastases: median overall survival was 20 months for patients with synchronous metastases compared to 63 months for those without. Fewer than 20% of patients were eligible for surgical treatment, underscoring the major negative prognostic impact of peritoneal dissemination. Part II evaluates HIPEC-based treatment strategies. Chapter 3 presents a systematic review comparing oxaliplatin and mitomycin C in cytoreductive surgery (CRS) combined with HIPEC. Although patient populations were comparable in disease extent, substantial differences in treatment protocols—such as use of neoadjuvant chemotherapy, HIPEC duration, and completeness of cytoreduction—limited direct comparison of outcomes. No clear conclusions could be drawn regarding disease-free or overall survival. However, oxaliplatin-based HIPEC appeared to be associated with higher rates of severe postoperative complications. The COLOPEC trial assessed whether adjuvant HIPEC could prevent peritoneal metastases in high-risk colon cancer patients (e.g., T4 or perforated tumors). Chapter 4 reports that adjuvant HIPEC did not significantly improve 18-month peritoneal metastases-free survival compared to standard systemic chemotherapy alone (81% vs. 76%). Notably, early postoperative evaluation revealed that some patients already had undetected metastases, preventing administration of HIPEC. Chapter 5 presents long-term outcomes of the COLOPEC trial. No significant differences were observed in 5-year overall survival, disease-free survival, or peritoneal metastases-free survival between treatment groups. These results confirm that adjuvant HIPEC does not provide additional benefit in preventing peritoneal metastases in this setting. Part III focuses on improving classification and surgical approaches. Chapter 6 examines histopathological assessment of peritoneal involvement (pT4a). By measuring the distance between tumor cells and the peritoneal surface, an objective method for risk stratification was established. A cut-off value of 100 micrometers effectively distinguished patients with different risks of developing peritoneal metastases. This quantitative approach may replace subjective pathological interpretation and improve staging accuracy. Chapter 7 evaluates the effect of surgical technique on adhesion formation. Laparoscopic surgery resulted in significantly fewer and less severe adhesions compared to open surgery (48% vs. 88.5%). Open surgery was identified as an independent risk factor for adhesion formation and severity, as well as for complications during reoperation. Additionally, HIPEC without cytoreductive surgery did not increase adhesion risk. Conclusion: Locoregional recurrence and peritoneal metastases remain major challenges in colon cancer. Surgical treatment can provide durable disease control in selected patients with LRCC. Peritoneal metastases significantly worsen prognosis and are only surgically treatable in a minority of cases. Adjuvant HIPEC does not improve outcomes in preventing metastases. Advances in pathological assessment and minimally invasive surgery may improve patient selection, reduce complications, and enhance overall outcomes.