Analyzing the interaction between time to surgery and tumor burden score in hepatocellular carcinoma

Background: The effect of “time to surgery (TTS)” on outcomes for curative-intent hepatectomy of hepatocellular carcinoma (HCC) remains debated. The interaction between tumor burden score (TBS) and TTS remains unclear. We sought to evaluate the effects of TBS and TTS on long-term HCC outcomes. Methods: Patients with HCC who underwent curative-intent hepatectomy (2000–2022) were analyzed from a multi-institutional database and categorized by TTS (≤60 or >60 days). Overall survival (OS) and cancer-specific survival were assessed. Results: Among 910 patients, median TTS estimates were 22 days in the short TTS group (n = 485) and 120 days in the long TTS group (n = 425). Patients with long TTS were older and were more likely to have American Society of Anesthesiologists class >2, diabetes mellitus, and cirrhosis. There was no difference in median TBS among patients who had short versus long TTS (4.61 vs 5.00, respectively). In addition, there was no difference in 5-year OS (70.0% vs 63.1%, respectively; P =.05). On multivariate analysis TBS (hazard ratio [HR], 1.07; 95% CI, 1.03–1.11; P <.001), log alpha-fetoprotein (HR, 1.08; 95% CI, 1.01–1.14; P =.02), and albumin-bilirubin score (HR, 2.52; 95% CI, 1.66–3.82; P <.001) were associated with OS. In contrast, TTS was not associated with OS (HR, 1.18; 95% CI, 0.78–1.77; P =.43). Interaction analysis demonstrated that TBS was asssociated with OS among patients with short TTS (HR, 1.12; 95% CI, 1.07–1.17; P <.001), but not among patients with long TTS (HR, 0.98; 95% CI, 0.91–1.05; P =.56). Among patients with low TBS (≤5), higher mortality was observed with long TTS versus short TTS (5-year OS: 82.4% vs 63.0%, respectively; P =.001); however, TTS was not associated with OS among patients with high TBS (5-year OS: 57.9% vs 63.3%, respectively; P =.92). Multivariate analysis demonstrated that long TTS was a risk factor for OS among patients with low TBS (HR, 3.12; 95% CI, 1.60–6.01; P <.001), but not among individuals with high TBS (HR, 0.57; 95% CI, 0.30–1.07; P =.08). Similar trends were observed relative to cancer-specific survival. Conclusion: TTS needs to be considered in light of patient and tumor-specific factors. Expediting TTS may be particularly important among patients with HCC and a low TBS.