Continuation of first-line therapy with radiotherapy for oligoprogression versus early switch to second-line therapy in oligoprogressive hepatocellular carcinoma (CROSS): study protocol of a multicentre, randomised, controlled, open-label, phase III trial

Introduction Treatment options remain limited for patients with advanced hepatocellular carcinoma (HCC) who experience oligoprogression during first-line systemic therapy (FLST), especially given the modest efficacy and restricted availability of second-line systemic therapy (SLST). This trial aims to evaluate whether continuing FLST combined with radiotherapy (RT) to oligoprogressive lesions can improve progression-free survival (PFS) compared with an early switch to SLST in patients with oligoprogressive HCC while maintaining an acceptable safety profile.

Methods and analysis The continuation of first-line therapy with radiotherapy for oligoprogression versus early switch to second-line therapy in oligoprogressive hepatocellular carcinoma trial is a prospective, multicentre, randomised phase III study that will enrol 132 patients with advanced HCC who experience their first oligoprogression during FLST. Oligoprogression is defined as one to five progressive lesions involving no more than one to three organs.

Participants will be randomised (1:1) to either continuation of FLST combined with RT to all oligoprogressive lesions or discontinuation of FLST followed by initiation of SLST.