Simple SummaryHepatocellular carcinoma (HCC) tumor burden score (TBS) and alpha-fetoprotein (AFP) have been considered important predictors of outcomes among patients with resectable HCC; yet, the interplay of TBS (i.e., tumor morphology) and AFP (i.e., surrogate for tumor biology) in HCC has not been examined to date. The current study aimed to investigate the interplay of HCC TBS and AFP among patients undergoing resection for HCC. Both TBS and serum AFP levels were strong predictors of outcomes and demonstrated a synergistic impact on prognosis, with higher serum AFP predicting worse outcomes among patients with HCC of a certain TBS class after resection. Both tumor morphology (i.e., tumor burden) and tumor-specific biomarkers (i.e., serum AFP) may be important when assessing the prognosis of patients who undergo resection for HCC.Introduction: The prognostic role of tumor burden score (TBS) relative to pre-operative alpha -fetoprotein (AFP) levels among patients undergoing curative-intent resection of HCC has not been examined. Methods: Patients who underwent curative-intent resection of HCC between 2000 and 2017 were identified from a multi-institutional database. The impact of TBS on overall survival (OS) and cumulative recurrence relative to serum AFP levels was assessed. Results: Among 898 patients, 233 (25.9%) patients had low TBS, 572 (63.7%) had medium TBS and 93 (10.4%) had high TBS. Both TBS (5-year OS; low TBS: 76.9%, medium TBS: 60.9%, high TBS: 39.1%) and AFP (>400 ng/mL vs. <400 ng/mL: 48.5% vs. 66.1%) were strong predictors of outcomes (both p < 0.001). Lower TBS was associated with better OS among patients with both low (5-year OS, low-medium TBS: 68.0% vs. high TBS: 47.7%, p < 0.001) and high AFP levels (5-year OS, low-medium TBS: 53.7% vs. high TBS: not reached, p < 0.001). Patients with low-medium TBS/high AFP had worse OS compared with individuals with low-medium TBS/low AFP (5-year OS, 53.7% vs. 68.0%, p = 0.003). Similarly, patients with high TBS/high AFP had worse outcomes compared with patients with high TBS/low AFP (5-year OS, not reached vs. 47.7%, p = 0.015). Patients with high TBS/low AFP and low TBS/high AFP had comparable outcomes (5-year OS, 47.7% vs. 53.7%, p = 0.24). The positive predictive value of certain TBS groups relative to the risk of early recurrence and 5-year mortality after HCC resection increased with higher AFP levels. Conclusion: Both TBS and serum AFP were important predictors of prognosis among patients with resectable HCC. Serum AFP and TBS had a synergistic impact on prognosis following HCC resection with higher serum AFP predicting worse outcomes among patients with HCC of a certain TBS class.
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