The Impact of Spatiotemporal Patterns of Tumor Recurrence on Prognosis in Hepatocellular Carcinoma Patients Undergoing Surgery After Conversion Therapy

Zhihong Chen,* Han Zheng,* Mingjian Piao,* Longhao Zhang, Yuxiao Sun, Kai Zhang, Junwei Zhang, Yaoge Liu, Yiyao Xu, Xin Lu Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yiyao Xu, Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of China, Email [email protected] Xin Lu, Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of China, Email [email protected]: To characterize the spatiotemporal patterns of recurrence and assess their impact on survival in hepatocellular carcinoma (HCC) patients undergoing curative resection after conversion therapy.Methods: We retrospectively analyzed 80 HCC patients who achieved successful conversion and underwent resection between January 2019 and February 2025. Recurrence was classified by timing (early ≤ 10.5 months vs. late > 10.5 months, determined by maximally selected log-rank statistics) and location (intrahepatic vs. extrahepatic) of the first recurrence. Exploratory analyses were also conducted using a 12-month cutoff to align with clinical practice. Post-recurrence survival (PRS), overall survival, and recurrence-free survival were evaluated using Kaplan-Meier analysis. The multivariable Cox models were used to calculate the adjusted hazard ratio and 95% confidence interval for PRS.Results: Recurrence occurred in 52.5% of patients. Early recurrence was associated with significantly worse PRS than late recurrence (P = 0.04). Although no significant difference in PRS was observed between subgroups when using a 12-month cutoff (P = 0.1) for the small sample size, this factor still showed a trend toward significance. Extrahepatic recurrence conferred poorer survival than intrahepatic recurrence (P < 0.0001). Combined spatiotemporal analysis revealed that early extrahepatic recurrence had the worst prognosis, while all late recurrences showed favorable outcomes. Multivariable Cox regression analysis confirmed that the later time recurrence was independently associated with better PRS.Conclusion: In this cohort, time to recurrence is the dominant prognostic factor, with recurrence site providing additional stratification. These findings support the use of spatiotemporal recurrence patterns for risk-adapted surveillance and adjuvant strategies.Keywords: hepatocellular carcinoma, conversion therapy, surgical resection, patterns of recurrence, survival prognosis