The therapeutic paradigm of liver surgery in the era of conversion therapy

Surgical resection remains the best approach for achieving long-term survival in patients with hepatocellular carcinoma （HCC）； however， due to the low early diagnosis rate of HCC patients in China， only 15%-20% of the patients are eligible for surgical resection at the time of initial diagnosis. Even for the patients undergoing surgery， the 5-year recurrence rate after surgery is as high as 50%-70%， resulting in an unsatisfactory prognosis. In recent years， the advances in systemic therapies， especially targeted therapy combined with immunotherapy， have not only extended the survival of patients with advanced liver cancer， but also promoted the application of systemic therapy in the earlier stages of HCC. On the one hand， the progress in systemic therapy has made conversion therapy a possible option for HCC， allowing a substantial number of patients with unresectable HCC at initial diagnosis to get the opportunity for surgical resection after downstaging and achieve a survival rate similar to those with resectable early-stage HCC at initial diagnosis； on the other hand， effective systemic therapy is being applied as neoadjuvant and adjuvant therapies for patients with resectable HCC， aiming to increase the R0 resection rate， reduce postoperative recurrence， and improve overall survival. Meanwhile， it should be clearly noted that although the advances in systemic therapy have significantly altered conventional surgical treatment paradigms， most clinical studies on conversion therapy， neoadjuvant therapy， and adjuvant therapy are small-scale phase II trials， with limited high-grade evidence from evidence-based medicine. It is important to select a reasonable therapeutic goal and develop an individualized treatment regimen based on the characteristics of tumor， and further explorations are needed to search for new biomarkers for predicting the efficacy of conversion therapy and perioperative treatment and identify the population with true benefits.