Three-month versus six-month duration of postoperative adjuvant therapy after R0 resection following conversion therapy in hepatocellular carcinoma patients achieving MPR or pCR: A prospective randomized study.

4121 Background: Conversion therapy allows a subset of patients with initially unresectable hepatocellular carcinoma (uHCC) to achieve a deep pathological response, enabling curative resection. However, the optimal duration of postoperative adjuvant therapy remains unclear. This prospective randomized study compared recurrence-free survival (RFS) and overall survival (OS) between 3-month and 6-month durations of postoperative adjuvant therapy after R0 resection in patients achieving major pathological response (MPR; ≥90% tumor necrosis) or pathological complete response (pCR). Methods: This randomized controlled trial (ChiCTR2100051789) enrolled patients with uHCC who achieved a MPR or pCR following conversion therapy. Eligibility criteria included pathological confirmation of MPR or pCR after R0 resection. Eligible patients were randomized 1:1 to receive 3 months (Group 3M) or 6 months (Group 6M) of postoperative adjuvant therapy starting 1 month after surgery. The primary endpoint was RFS; secondary endpoints included OS and recurrence patterns. Results: Between January 15, 2022, and April 20, 2025, 58 patients were randomized (29 per group). Pathological evaluation confirmed MPR in 21 patients and pCR in 37 patients. After a median follow-up of 33.05 months, recurrence occurred in 8 patients. The 1-, 2-, and 3-year RFS rates were 89.3%, 89.3%, and 78.8% in Group 3M and 88.9%, 88.9%, and 88.9% in Group 6M (P = 0.592). Corresponding OS rates were 100%, 96.4%, and 96.4% versus 100%, 91.8%, and 91.8%, respectively (P = 0.451). Conclusions: In patients with uHCC who achieved a deep pathological response (MPR or pCR) after conversion therapy, a shorter duration of adjuvant therapy may be sufficient, with a 3-month course providing survival outcomes comparable to those of a 6-month course. Clinical trial information: ChiCTR2100051789.