TRANsplantation vs reSECTion After Conversion Therapy for Initially Unresectable
The TRANSECT trial is a prospective randomized study designed to evaluate the role of liver transplantation (LT) versus radical local treatment (hepatic resection and/or ablation) in patients with initially unresectable colorectal liver metastases (CRLM) converted to resectability after conversion therapy. Liver metastases are the leading cause of mortality in colorectal cancer patients. Although hepatic resection combined with chemotherapy remains the standard curative-intent treatment, only a minority of patients are eligible for upfront surgery. Advances in modern conversion chemotherapy have substantially increased the proportion of patients who can subsequently undergo curative local treatment. However, liver resection after intensive chemotherapy is still associated with high rates of intrahepatic recurrence, risk of R1 resections, chemotherapy-induced liver injury, and the need for complex surgical procedures carrying considerable morbidity and mortality. In parallel, recent studies investigating LT for unresectable CRLM, including the TRANSMET trial, demonstrated highly promising oncological outcomes, with 5-year overall survival rates exceeding 50% in selected patients. Based on these findings, the TRANSECT trial hypothesizes that LT may represent a more effective therapeutic strategy also in patients initially deemed unresectable but subsequently converted to resectability, by completely removing the hepatic metastatic niche. TRANSECT is a single-center, randomized, open-label, proof-of-concept trial. Patients with liver-only CRLM initially assessed as unresectable by a dedicated multidisciplinary tumor board and subsequently converted to resectability after systemic therapy will be randomized to either LT or hepatic resection and/or ablation. The primary endpoint is 3-year intention-to-treat overall survival (OS). Secondary endpoints include perioperative morbidity and mortality, disease-free survival, treatment adherence, quality of life, and exploratory translational analyses including radiomics and circulating tumor DNA assessment. A total of 70 patients (35 per arm) will be enrolled, with an estimated overall study duration of 5 years. TRANSECT represents the first randomized trial directly comparing LT and liver-directed surgery in patients with initially unresectable CRLM converted to resectability after systemic therapy, with the aim of redefining curative treatment strategies in this selected patient population.
• Signed screening phase informed consent.
• Age \>18.
• Performance status score of Eastern Cooperative Oncology Group (PS-ECOG) 0-1
• Adequate organ functions.
• Liver-limited Metastatic Disease Confirmed as Unresectable by Colorectal Oncology Multidisciplinary Tumor Board (MTB).
• Histologically documented adenocarcinoma of the colon or intra-peritoneal rectum
• Absence of extra-hepatic disease demonstrated by contrast-enhanced CT + MRI and, in clinically indicated (clinical suspicion or elevated biomarkers), FDG-PET.
• No previous systemic treatment for unresectable disease.
• No previous systemic treatment for primary tumor resection
• Recurrence occurring beyond six months after completion of adjuvant treatment.
• MMR proficient cancer (MSS) regardless of RAS mutational status, BRAF-WT except for BRAF V600E-mut treated and responding to anti-BRAF + cytotoxic therapy.