Clinical Outcomes of AFP-Negative Patients with Advanced HCC: A Propensity-Matched Analysis from a Retrospective Cohort Study.

INTRODUCTION

AFP positivity (≥20 ng/mL) is often used as one of the diagnostic criteria for HCC. The aim of this study is to analyze the prognosis of advanced HCC with negative (<20 ng/mL) AFP at baseline following systemic drug treatment.

METHODS

In this study, 91 patients with AFP-negative advanced HCC who received systemic drug treatment in Nanjing Jinling Hospital from February 2011 to September 2023 were collected, and 213 patients with AFP-positive advanced HCC were collected as the control group. A propensity score model was used to adjust for potential confounding variables. Cox regression analysis was used to clarify the differences of prognosis in subgroups for HCC patients.

RESULTS

Following propensity score matching with 1:2 ratio, 90 HCC patients from Group A (AFP-negative) and 180 from Group B (AFP-positive) were chosen to participate in the final analysis set. The OS of AFP-negative HCC patients was extended by 13.5 months compared to AFP-positive HCC patients. Within the AFP-negative HCC group, the top-ranked first-line treatment options were TKIs combo ICIs (mPFS = 9.5m, mOS = 37.1m), chemotherapy combo ICIs (mPFS = 8.1m, mOS = 15.5m), and TKIs (mPFS = 5.6m, mOS = 28.2m). Subgroup analysis indicated that among AFP-negative HCC patients, those without PVTT or with HBV DNA <50lU/mL had longer survival time. For HCC patients who opted for TKIs combo ICIs as their first-line treatment and then switched to TKIs alone for second-line treatment, the mOS and 95% CI were 30.7 (24.8-NA) months.

CONCLUSION

The survival time of AFP-negative HCC patients was significantly longer than that of AFP positive HCC patients. Patients with no PVTT or HBV DNA <50lU/mL have relatively better efficacy of systemic drug therapy. With the AFP-negative HCC patients, TKIs combo ICIs are preferentially recommended for the first-line therapy, and TKIs are used for the second-line therapy after progression.