Reducing Immunosuppression in Patients with De Novo Lung Carcinoma after Liver Transplantation Could Significantly Prolong Survival

Abstract

Simple Summary: Long-term immunosuppressive therapy following liver transplantation is associated with an increased risk for the development of de novo lung carcinoma. However, data on the management of the immunosuppression following the diagnosis of lung cancer are missing to the present day. In this retrospective analysis, we investigate factors associated with improved survival of liver transplant recipients with diagnosis of de novo lung carcinoma with a particular emphasis on the impact of immunosuppression. Our findings suggest that strict reduction of immunosuppression has a beneficial effect on survival in this particular situation and, thus, should be an early intervention following diagnosis. Liver transplant recipients with the diagnosis of de novo lung cancer should be offered surgical treatment if technically feasible as a potential curative therapeutic option to improve limited prognosis. Further investigations concerning dosage findings and reduction of immunosuppression in organ recipients should be the targets of subsequent studies.

Abstract: (1) Background: Liver transplantation (LT) is an established treatment for selected patients with end-stage liver disease resulting in a subsequent need for long-term immunosuppressive therapy. With cumulative exposure to immunosuppression (IS), the risk for the development of de novo lung carcinoma increases. Due to limited therapy options and prognosis after diagnosis of lung cancer, the question of the mode and extent of IS in this particular situation is raised.

(2) Methods: All patients diagnosed with de novo lung cancer in the follow-up after LT were identified from the institution's register of liver allograft recipients (Charite-Universitatsmedizin Berlin, Germany) transplanted between 1988 and 2021. Survival analysis was performed based on the IS therapy following diagnosis of lung cancer and the oncological treatment approach.

(3) Results: Among 3207 adult LTs performed in 2644 patients at our institution, 62 patients (2.3%) developed de novo lung carcinoma following LT. Lung cancer was diagnosed at a median interval of 9.7 years after LT (range 0.7-27.0 years). Median survival after diagnosis of lung carcinoma was 13.2 months (range 0-196 months). Surgical approach with curative intent significantly prolonged survival rates compared to palliative treatment (median 67.4 months vs. 6.4 months). Reduction of IS facilitated a significant improvement in survival (median 38.6 months vs. 6.7 months). In six patients (9.7%) complete IS weaning was achieved with unimpaired liver allograft function.

(4) Conclusion: Reduction of IS therapy after the diagnosis of de novo lung cancer in LT patients is associated with prolonged survival. The risk of acute rejection does not appear to be increased with restrictive IS management. Therefore, strict reduction of IS should be an early intervention following diagnosis. In addition, surgical resection should be attempted, if technically feasible and oncologically meaningful.