Is Cytoreductive Surgery for Unresectable Colorectal Liver Metastases Able to Improve Patient Outcome? Results of a Pilot Prospective Study

BACKGROUND:Curative R0-R1 resection is not always feasible in patients with extensive bilobar colorectal liver metastases (CRLM). When unresectatility is confirmed, the standard of care is palliative chemotherapy or more recently liver transplantation (LT) with very restrictive eligibility criteria. This exploratory study evaluated cytoreductive surgery as an alternative to chemotherapy alone in patients with initially unresectable CRLM responding well to systemic chemotherapy but ineligible to LT. METHODS:This prospective study (January 2017-January 2024) included patients with permanently unresectable CRLM involving >6 segments, with or without limited extrahepatic metastases. Those achieving a sustained partial response on RECIST criteria after ≥3 months of chemotherapy and not amenable to LT, underwent cytoreductive surgery defined as resecting or ablating all visible residual lesions while leaving disappearing liver metastases (DLMs) untreated-The primary endpoint was 5-year overall survival (OS); secondary endpoints included disease-free survival (DFS) and time to surgical failure (TSF). RESULTS:Of 330 patients undergoing CRLM resection, 33 were eligible, and 28 underwent cytoreductive surgery (18 major, 10 limited hepatectomies, frequently with ablation). Grade ≥ III complications at 3 months occurred in 4 patients (14%), including one mortality (3.6%). At 57- month median follow-up, 5-year OS was 47% (whole cohort) and 64% (operated patients), respectively. Liver recurrence occurred in 22 patients (79%), with a 5-year DFS of 17%. Recurrences were frequently managed with repeat hepatectomy and/or ablation, including second (n = 15) and third (n = 7) hepatectomies, resulting in a 5-year TSF rate of 36%. CONCLUSIONS:Cytoreductive surgery combined with chemotherapy is a strategy that may improve long-term survival in selected patients with unresectable CRLM. This favorable outcome is likely driven by highly selected tumor biology, by sustained response to chemotherapy and by the feasibility of repeat surgical resections for recurrences, rather than by the initial surgery alone.