Observation vs Surgical Resection for Initial Unresectable Hepatocellular Carcinoma after Conversion Therapy

Background

Hepatocellular carcinoma (HCC) is the sixth most common cancer globally and the third leading cause of cancer-related mortality. Partial hepatectomy can provide a 5-year survival rate of 70-80% in the treatment of early-stage HCC. However, due to advanced tumor staging, poor liver function, and insufficient residual liver volume, many HCC patients miss the opportunity for surgical resection, with a resection rate of less than 40%. Conversion therapy can turn unresectable or marginally resectable HCC tumors into resectable ones, thereby improving patient survival.

In recent years, the treatment of unresectable HCC using anti-angiogenic drugs and immune checkpoint inhibitors (ICIs) has made significant progress, with an objective response rate (ORR) of approximately 30%. Additionally, the use of transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) has further increased the ORR and tumor shrinkage rate. However, for patients who achieve radiologic complete response (RCR) or clinical complete response (CCR) after conversion therapy, the optimal subsequent treatment strategy remains unclear. This study aims to evaluate the feasibility and outcomes of the watch-and-wait (W-W) strategy compared with surgical resection (SR) for these patients.

Source of the Study

The authors of this study include Binkui Li, Chenwei Wang, Wei He, Jiliang Qiu, Yun Zheng, Ruhai Zou, Zhu Lin, Yunxing Shi, Yichuan Yuan, Rong Zhang, Chao Zhang, Minshan Chen, Wan Yee Lau, and Yunfei Yuan, affiliated with the Cancer Center of Sun Yat-sen University and The Chinese University of Hong Kong. The study was published on February 8, 2024, in the International Journal of Surgery.

Study Procedure

This was a retrospective study that included 1,880 patients with initially unresectable HCC who received conversion therapy, of which 207 (11.0%) achieved RCR. After further screening, 149 patients were eligible for inclusion, with 74 patients receiving the W-W strategy and 75 patients undergoing SR.

1. Patients and Grouping: The study included patients with initially unresectable HCC who received conversion therapy between January 2016 and December 2020, meeting a series of strict inclusion and exclusion criteria.
2. Conversion Therapy Methods: Included TACE or HAIC combined or not combined with systemic therapy (such as TKIs and PD-1 antibodies). Treatment intervals were every 3-4 weeks, with the goal of achieving RCR.
3. Imaging and Pathological Evaluation: Tumor response was evaluated using mRECIST criteria, with RCR defined as the disappearance of arterial enhancement in all target lesions. CCR criteria included RCR, no distant metastasis, and normal AFP levels, maintained during follow-up.
4. Surgical Resection: For patients who achieved RCR but still required further treatment, a multidisciplinary team comprehensively evaluated them to ensure that surgical resection could achieve an R0 margin and preserve at least 30-40% of the residual liver volume.

Main Results

Among the 149 patients with RCR after conversion therapy, the W-W group and the SR group had similar 3-year overall survival rates (80.9% vs. 83.1%, P=0.77), but the W-W group had significantly lower progression-free survival (PFS) rates (14.4% vs. 46.5%, P=0.002) compared to the SR group. This difference persisted after propensity score matching.

For the 57 patients who achieved CCR, there were no significant differences between the W-W group and the SR group in terms of 3-year overall survival (88.1% vs. 87.9%, P=0.89) and progression-free survival (27.8% vs. 40.8%, P=0.34).

Among the 75 patients in the SR group, 31 (41.3%) achieved pathologic complete response (PCR), while 44 (58.7%) did not achieve PCR. Comparative analysis showed that the RCR patients in the W-W group had no significant difference in overall survival compared to the PCR patients in the SR group, but had lower progression-free survival. Compared to the non-PCR patients in the SR group, the W-W group showed no significant differences in both overall survival and progression-free survival.

Conclusion and Significance

This study suggests that for initially unresectable HCC patients who achieve RCR or CCR after conversion therapy, the W-W strategy can provide overall survival rates similar to SR. However, the W-W strategy is inferior to SR in terms of progression-free survival. For these patients, the W-W strategy can serve as an alternative treatment option, especially for those unwilling to undergo surgical resection.

Research Highlights

1. Similar Overall Survival: The study found no significant difference in overall survival between the W-W strategy and SR, which is an important finding, suggesting that the W-W strategy can be an alternative to SR under certain conditions.
2. Differences in Progression-Free Survival: Although the W-W strategy had similar overall survival to SR, it was inferior in terms of progression-free survival, indicating the need for more standardized follow-up and timely intervention.
3. Precise Patient Selection: The study emphasizes the importance of reasonably selecting suitable patients for the W-W strategy, particularly those with initially negative AFP levels and receiving combination therapy, where the W-W strategy may be more meaningful.
4. Future Research Directions: This study provides valuable experience and data support for future research on MRD management and treatment optimization.

Through detailed and systematic evaluation and analysis, this study provides new perspectives and scientific evidence for formulating HCC treatment strategies, with significant clinical guidance and practical value.