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A 7-cm inflection point: nonlinear association between maximum tumor diameter and capsular invasion risk after
Ye Zhang1,2,3,4, Gongming Zhang5, Xin Wang6
1Department of Respiratory and Critical Care Medicine, Beijing You'an Hospital, Capital Medical University, Beijing, 100069, P.R. China.
Background:
Capsular invasion independently predicts poor prognosis after primary liver cancer (PLC). While maximum tumor diameter (MTD) informs staging systems, its potential nonlinear association with capsular invasion remains unquantified.
Methods:
This retrospective cohort study analyzed 1,380 consecutive patients undergoing curative liver resection for primary liver cancer (2008-2025). Multivariable logistic regression and restricted cubic splines (RCS) were used to model the MTD-capsular invasion relationship, adjusting for demographics, comorbidities, laboratory indices, and tumor characteristics.
Results:
MTD exhibited a significant nonlinear, threshold-dependent association with capsular invasion (likelihood ratio test P = 0.011). For tumors ≤ 7 cm, each 1-cm increase in MTD increased the odds of capsular invasion by 15.4% (adjusted odds ratio [aOR] = 1.154, 95% confidence interval [CI]: 1.029-1.296; P = 0.0147). Conversely, for tumors ≥ 7 cm, no significant association was observed (aOR = 0.926, 95% CI: 0.832-1.031; P = 0.162). Furthermore, the association remained robust across all clinical subgroups (all interaction P > 0.05) and was confirmed by multiple sensitivity analyses.
Conclusions:
This study identifies a 7-cm inflection point in the association between maximum tumor diameter and capsular invasion risk for resectable primary liver cancer. The relationship is characterized by a progressive increase in risk below this threshold, which stabilizes for tumors larger than 7 cm. These hypothesis-generating findings question the prevailing linear size-risk assumptions and underscore the need for future validation using preoperative imaging and prospective studies with long-term follow-up to evaluate its impact on patient prognosis.
