This clinical controlled study clearly demonstrated the better parenchymal tolerance to IPC over CPC, especially in patients with abnormal liver parenchyma.

Liver metastasis represents the major cause of death of patients who have been treated for colorectal adenocarcinoma. Spontaneous survival rarely exceeds two years. Surgery can offer long-term survival and resection should be considered when liver metastases can be totally resected with clear margins and when there is no non-resectable extra-hepatic disease. The choice between anatomical or wedge resection depends on the number and the location of the metastases but does not influence survival. Clamping methods limit blood loss. Operative mortality is generally less than 5%. The five-year survival rate after surgical resection varies from 20% to 45% according to several prognostic factors. The longer survival is observed in patients with fewer than four lesions, with lesions smaller than 4 cm, without extra-hepatic disease, with lesions that appeared more than two years after the resection of a stage I or II colorectal cancer and whose CEA level is normal. After resection, follow-up can detect hepatic recurrence that can be treated with repeat hepatectomy. The efficacy of systemic chemotherapy using new agents can increase the number of patients amenable to surgery. Regional therapies with cryotherapy or radiofrequency ablation can help to treat unresectable or non-totally resectable lesions and may improve survival. The effects on survival of adjuvant treatments, including pre- or postoperative systemic or postoperative intra-arterial chemotherapy, are currently under evaluation.

Radiofrequency ablation (RFA) of colorectal liver metastases activates a specific T-cell response that is ineffective in avoiding recurrence. Recently, local immunomodulation garnered interests as a way to improve the immune response. We were interested in improving the RFA immune response priming to propose a curative treatment of colorectal cancer (CRC) based on antitumor immunity. First, we demonstrated that the RFA did not increase the tumor infiltrating lymphocytes in secondary distant tumors of patients and in mice model and could not avoid relapse. Remarkably, RFA and in situ immunomodulation with GM-CSF-BCG hydrogel induced complete cure of microscopic secondary lesions in mice, related to a strong specific immune response. Then, we demonstrated that the immune escape of large secondary lesions was reversed by addition of the systemic PD-1 blockade to the in situ immunomodulation. The lack of an effective distant immune response in patients treated with RFA confirmed the relevance of this new combination strategy. Increasing the in situ priming response of radiofrequency ablation provides effective adjuvants to induce an abscopal effect. In the case of large lesions, synergy between PD1 blockade inhibitor, ineffective alone or after single RFA, with in situ immunomodulation, could lead to reconsideration of the use of checkpoint inhibition in metastatic MSS CRC.