Neoadjuvant downstaging in primary liver cancer

Introduction: Primary liver cancer remains the third leading cause of cancer related death with incidence and mortality rates on the rise. Improving overall survival, immune-checkpoint inhibitors (ICI) have become a cornerstone of systemic treatment combinations for advanced stage disease. In some cases, these treatments can elicit significant tumor size reduction thereby enabling subsequent resection with curative intent. From a prognostic perspective it remains unclear whether outcomes after secondary resection are comparable to those achieved through primary resection.

Methods and Aims: We conducted a retrospective analysis of all patients undergoing systemic therapy for either hepatocellular carcinoma (HCC) or intrahepatic/perihilar cholangiocarcinoma (iCC/pCC) since 2021 and analyzed clinicopathological data as well as oncological outcomes with the aim of defining the potential benefit of secondary resectability.

Results: Of all patients undergoing systemic therapy for HCC or iCC/pCC downstaging to resectable disease was achieved in 18 patients with primary liver cancer (7 HCC; 11 CCC) who received ICI-based treatment combinations due to either advanced stage disease or technical inoperability and were rendered suitable for curative-intent resection subsequently. In all 18 patients, R0 resection was achieved. 17 patients showed a reduction in tumor size and five met the criteria for objective response according to RECIST 1.1. Pathological assessment revealed a major pathological response, defined as≥70% tumor necrosis, in six patients. Mean follow up was 8 months. Recurrence occurred in three patients after a median recurrence-free survival (RFS) of 11 months. Two patients died during follow up, one in the post-operative interval due to complications and one due to tumor progression 8 months after surgery. None of the patients with recurrence had objective response after neoadjuvant treatment.

Interpretation: ICI treatment of primary liver cancer can enhance access to curative treatment, enabling R0 resection in patients initially assessed as unsuitable for resection. Importantly, objective response was not a prerequisite for secondary resectability indicating radiologic response criteria alone may be too strict. Short term oncological outcomes showed promising RFS and overall survival data highlighting the potentially conducive effects of neoadjuvant downstaging treatment.

Publication History

Article published online:
04 September 2025