Pathological response ≥90% predicts survival in HCC treated with neoadjuvant loco-regional therapies: A retrospective...

Pathological response closely correlates with the prognosis of hepatocellular carcinoma (HCC), but assessing major pathological response (MPR) in patients with larger HCCs is challenging. Given that loco-regional therapies are widely used for larger HCCs, we aimed to determine the optimal cut-off for MPR in patients who received loco-regional therapies preoperatively.

Specimens from consecutive patients with HCC who underwent preoperative loco-regional therapies were included. The most representative sections with residual tumour were sampled. The MPR threshold was derived from the optimal cut-off for residual viable tumour for predicting overall survival (OS) in patients receiving loco-regional therapies only (Cohort 1) and was validated in those receiving loco-regional plus systemic therapies (Cohort 2). Factors associated with pathological response were evaluated using logistic regression models. Subgroup analyses were performed to explore differences in these related factors across subgroups.

A total of 6,530 samples from 303 patients were evaluated. With a median follow-up of 31.7 months, the 1- and 3-year overall survival (OS) rates were 92.5% and 73.8% for Cohort 1 (n = 191), and 89.2% and 73.9% for Cohort 2 (n = 112). In Cohort 1, 10% residual viable tumour was identified as the optimal cut-off for predicting better OS (hazard ratio [HR] 0.219; 95% CI 0.087-0.552; p <0.001). In Cohort 2, patients with pathological response ≥90% had superior OS (HR 0.242; 95% CI 0.125-0.467; p <0.001) and disease-free survival (HR 0.195; 95% CI 0.102-0.375; p <0.001). Additionally, complete/major pathological response was associated with better OS and disease-free survival in most subgroups.

We propose pathological response ≥90% as the threshold for defining MPR and as an appropriate surrogate endpoint for patients with HCC treated with loco-regional therapies when OS data are immature.

The lack of a consistent definition of major pathological response (MPR) across different clinical trials has made it difficult to evaluate and compare the efficacy of treatments for hepatocellular carcinoma (HCC). In addition, assessing the pathological response in patients with large HCC tumours is challenging. Here, we analysed the most representative sections containing residual tumour cells from patients who received preoperative loco-regional therapies. We identified 10% residual viable tumour as the threshold to define MPR in such cases. The significant positive correlation between complete pathological response/MPR and overall survival suggests that pathological response ≥90% is an appropriate surrogate endpoint for large HCC when overall survival data are immature.

This study has been registered at the Chinese Clinical Trial Registry (unique identifying number: ChiCTR2300076241, https://www.chictr.org.cn/showprojEN.html?proj=208162).