E254: Survival and Downstaging After Neoadjuvant Therapy for Hepatocellular Carcinoma: A Propensity-Matched Analysis of the National Cancer Database

Various modalities of neoadjuvant therapy (NAT) are used in the treatment of hepatocellular carcinoma (HCC) to downstage tumors and decrease recurrence. However, there is still no robust data to support or consensus upon the indications for NAT prior to liver resection. We aimed to compare survival and downstaging rates between patients with HCC who received NAT vs. upfront surgery.

Methods: A retrospective cohort study of subjects with clinical stage I-III HCC undergoing liver resection (non-transplant) was performed using the 2004-2020 National Cancer Database (NCDB). Subjects were stratified by receipt of NAT. Transarterial chemoembolization (TACE) is coded as systemic therapy in the NCDB. Propensity score matching (PSM) for receiving NAT was performed 1:1 based upon age, comorbidity status, and clinical stage. Primary outcomes were 30-day and 90-day mortality, overall survival, and clinical-to-pathological downstaging rate.

Results:

We identified 1,989 patients with resected HCC, with 938 (47.2%) receiving NAT. In this unmatched cohort, overall survival was significantly longer in the NAT group (79 vs. 34 mos, p< 0.001) although 30-day mortality was also higher with NAT (4.2% vs. 2.4%, p=0.01). After PSM, there were 1,202 patients with 601 (50%) receiving NAT. Of the NAT group, 597 (99.3%) received neoadjuvant systemic therapy or TACE, including 6 (1%) who received neoadjuvant immunotherapy; 32 (5.3%) received neoadjuvant radiation and 102 (17.0%) received multiple modalities of treatment. The R0 resection rate was 95.2% after NAT vs. 85.9% in the upfront surgery group (p< 0.001). Downstaging occurred in 10.3% among those receiving NAT and 5.5% in the upfront surgery group (p< 0.001). After PSM, 30- and 90-day mortality were not significantly different between the two groups. Median 5-year overall survival was improved with NAT vs. upfront surgery (75 vs. 36 mos, p< 0.001). Median survival in patients receiving multimodality NAT was 86.3 months, compared to 75.2 months in those receiving systemic NAT+TACE alone (n=493) and 26.6 months in patients receiving neoadjuvant radiation alone (n=6) (p< 0.001). Downstaging was not associated with improved survival (65 vs. 48 mos, p=0.08).

Conclusions:

In an era before widespread adoption of immunotherapy for HCC, p</span>atients with HCC who received NAT had significantly improved survival compared to those undergoing upfront surgery with similar short-term mortality. Neoadjuvant treatment is also associated with a modest downstaging rate but downstaging was not correlated with improved survival.