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.
Absolute contraindication to liver transplant.
Other malignancies in the previous 5 years excluding non melanoma skin-cancers or in situ disease.
Hereditary CRC syndromes including FAP and Lynch syndrome.
Previous extrahepatic metastatic localization or locoregional tumor recurrence.
Parallel
Liver Transplantation
Procedure/SurgeryOrthotopic liver transplantation performed in patients with colorectal liver metastases after successful conversion to resectability following systemic therapy. Eligibility for transplantation is confirmed through multidisciplinary evaluation and restaging. Patients continue systemic therapy after randomization until listing for transplantation or until the date of the procedure is established. Postoperative management includes standard immunosuppressive therapy and oncologic follow-up according to institutional protocols
Liver Resection plus Ablation
Procedure/SurgeryLiver resection with or without ablative techniques in patients with colorectal liver metastases after successful conversion to resectability following systemic therapy. Patients continue systemic therapy after randomization until the surgical procedure is performed, according to protocol. The surgical strategy is determined by a multidisciplinary team with the aim of achieving complete tumor removal (R0 resection). Perioperative and postoperative management follow standard institutional practice
Overall Survival (OS)
Overall survival will be measured from the date of randomization to death from any cause and analyzed according to the intention-to-treat principle.
Disease-Free Survival (DFS)
Disease-free survival is defined as the time from the date of treatment (liver transplantation or hepatic resection ± ablation) to the date of tumor recurrence or death from any cause, whichever occurs first.
Perioperative Morbidity
Assessment of postoperative complications occurring within 90 days after liver transplantation or hepatic resection + ablation, graded according to standard clinical classifications.
Perioperative Mortality
All-cause mortality occurring within 90 days after liver transplantation or hepatic resection + ablation
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