Maintenance therapy in first remission for advanced fibrolamellar carcinoma

Background: Fibrolamellar carcinoma (FLC) is a rare primary liver malignancy affecting predominantly adolescents and young adults, with high recurrence rates even after complete macroscopic resection. Traditionally, surgical intervention alone was largely considered the only curative strategy. Research in recent years suggests the role of systemic therapy, however no consensus guidelines currently exist. This study evaluates progression-free survival (PFS) and overall survival (OS) after surgery, while incorporating stage, type of therapy, and resection margin status as prognostic factors. This is the first study to evaluate outcomes associated with maintenance/adjuvant therapy following surgical resection in a real-world FLC cohort. Methods: We analyzed 207 patients with FLC who underwent surgical resection in a retrospective multicenter dataset. Adjuvant systemic therapy was categorized as “none,” “chemotherapy,” or “immunotherapy.” Endpoints included PFS and OS calculated from date of surgery. Kaplan-Meier estimates and log-rank tests assessed unadjusted differences. Multivariable Cox proportional hazards models evaluated the independent effects of therapy type, stage (Localized = Stage 1, Regional = Stages 2 & 3, Metastatic = Stage 4), and margin status (R0 = NED, R1 =Microscopic Disease, R2 = Gross Disease Remains). Results: A total of 200 patients were evaluable for PFS (163 progression events) and 199 for OS (75 deaths). Stage was the strongest predictor of outcome: metastatic disease was associated with an 8.6-fold higher hazard of progression and a 47.7-fold higher hazard of death relative to localized disease. Margin status was prognostic, with R2 resections conferring a significantly increased hazard of death (HR 2.87, 95% CI 1.50-5.47).Adjuvant systemic therapy was independently associated with prolonged PFS after adjusting for stage and margin. Compared with no therapy, chemotherapy (HR 0.44, 95% CI 0.25-0.75) and immunotherapy (HR 0.41, 95% CI 0.26-0.66) both benefitted metastatic patients. Although there was no statistical significance in OS for chemotherapy or immunotherapy, this is likely the result of other factors and suggests need for additional study. Conclusions: In this large real-world surgical cohort of FLC patients, postoperative chemotherapy and immunotherapy were independently associated with reduced risk of progression, with the most pronounced benefit in metastatic disease. OS was driven primarily by disease stage and margin status. These findings suggest a potential role for postoperative systemic therapy in patients with advanced FLC and highlight the critical importance of achieving negative surgical margins. Prospective studies are needed to validate these results and define evidence-based guidelines.