Maintaining first-line therapy plus radiotherapy may prolong progression-free survival and delay second-line therapy for oligoprogressive hepatocellular carcinoma.

Purpose: Optimal treatment strategies for patients with hepatocellular carcinoma (HCC) with oligoprogression after first-line systemic therapy (FLST) remain undefined. We aimed to determine if maintaining [i.e., continuing] FLST plus radiotherapy for oligoprogressive lesions (m-FLST + RT) would result in progression-free survival (PFS) equal to or greater than that of second-line systemic therapy (s-SLST), either alone or with radiotherapy (s-SLST + RT).

Methods And Materials: From October 2018 to February 2024, 154 patients from seven medical centers who developed oligoprogression after FLST were enrolled and assigned to one of three groups based on post-oligoprogression treatment strategy: m-FLST + RT, s-SLST + RT, or s-SLST-only. The primary outcome was PFS, and early patterns of recurrence were noted.

Results: At a median follow-up time of 8.4 months, median PFS time was longer in the m-FLST + RT group (8.6 months) compared with the s-SLS-only group (3.1 months) (hazard ratio [HR] =3.163, 95% CI 2.133-4.690, p<0.001) and the s-SLST + RT group (5.8 months) (HR=2.183, 95% CI 1.110-4.293, p=0.006). Multivariate Cox analysis demonstrated that albumin-bilirubin (ALBI) grade and post-oligoprogression treatment strategy were independent prognostic factors for PFS. Stratified analysis by ALBI grade showed that m-FLST + RT resulted in significantly longer median PFS in both ALBI-1 and ALBI-2 patients compared with s-SLST-only (p<0.001). Regarding subsequent patterns of relapse, the m-FLST + RT group had a lower rate of re-enlargement of recently oligoprogressive lesions (27.6%) than the s-SLST + RT (31.8%) and s-SLST-only (50.0%) groups. It also had the lowest rate of re-enlargement of previously identified metastases that did not progress during FLST (13.8%) compared with s-SLRT + RT (27.3%) and s-SLST-only (24.4%).

Conclusions: Our study suggests a potential clinical benefit of m-FLST + RT without the need for s-SLST and provides insights to optimize treatment strategies for oligoprogressive HCC.