Conversion therapy, which aims to downstage initially unresectable hepatocellular carcinoma (uHCC) to enable curative resection, is gaining traction as a treatment strategy. A recent study published in BMC Gastroenterology investigates the outcomes of conversion therapy in a real-world setting, highlighting both its potential and limitations.
The study, conducted at a single center, retrospectively analyzed data from patients with uHCC who underwent conversion therapy. The results showed that approximately 1-2% of uHCC patients achieved successful conversion and subsequent R0 resection. This rate increased to 2.59% when patients received combination therapy involving both systemic and loco-regional approaches.
Efficacy of Conversion Therapy
The study found that among the 38 uHCC patients who underwent conversion therapy, a significant proportion experienced tumor reduction. Objective response rates (ORR) were 52.6% and 78.9% based on RECISTv1.1 and mRECIST criteria, respectively. Notably, 39.5% of patients achieved pathological complete response (pCR) following conversion surgery.
"The tumors of 38 uHCC patients included in this study responded well to conversion therapy, and 36 patients (94.7%) had tumor reduced," the authors stated. However, they also noted discrepancies between radiological and pathological responses, advocating for the development of more precise criteria for defining clinical complete response (cCR) in HCC.
Safety and Surgical Outcomes
While conversion therapy showed promising efficacy, it was also associated with increased surgical complexity. Patients undergoing conversion surgery experienced longer operation times and greater blood loss compared to those undergoing direct R0 resection. Postoperative hospital stays were also extended in the conversion surgery group.
However, the study also indicated that perioperative clinical practice for successful conversion patients is becoming more mature. Data from the most recent year showed shorter operative times and postoperative hospital stays compared to previous years, suggesting improved patient selection and treatment strategies.
Survival Prognosis
At a median follow-up of 19.3 months, the 1-year disease-free survival (DFS) rates for patients undergoing direct surgery and successful conversion surgery were 91.4% and 86.8%, respectively. These preliminary results suggest that the survival prognosis of patients undergoing successful conversion surgery is comparable to that of patients undergoing direct surgery.
Limitations and Future Directions
The authors acknowledged several limitations of the study, including its retrospective design, single-center experience, and relatively short follow-up duration. They also emphasized the inherent selection bias in conversion therapy, as it typically involves patients who respond best to anti-HCC treatments.
"Convertible uHCC patients are generally the minority segment that responds best to anti-HCC treatments," the authors noted. "Consequently, conversion therapy chooses tumors with advantageous biological characteristics, making it challenging to determine whether patients gain anything from surgery in the long run."
Despite these limitations, the study provides valuable insights into the real-world application of conversion therapy for uHCC. The findings underscore the potential of combination therapies to downstage tumors and enable curative resection in select patients. Further research, including prospective studies with longer follow-up periods, is needed to fully evaluate the long-term benefits of this approach.
