转化治疗时代的肝脏外科治疗模式

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

手术切除仍然是肝细胞癌(以下简称肝癌)患者获得长期生存的最佳方式。然而,我国肝癌患者由于早诊率低,初诊时仅有15%~20%的患者具备手术切除机会。即使是手术切除的患者,术后5年复发率高达50%~70%,预后不能令人满意。近年来以靶向联合免疫治疗为代表的系统治疗不断进步,不但使晚期肝癌患者的生存时间不断延长,系统治疗更在不断前移,应用于早中期肝癌的治疗。一方面,系统治疗的进步使得肝癌转化治疗成为可能,相当一部分初诊不可切除的患者经过转化降期后可以获得手术切除机会,并达到与初诊可切除早期肝癌患者类似的生存。另一方面,有效的系统治疗正在应用于可切除肝癌患者的新辅助治疗和辅助治疗,以期提高R0切除率,降低术后复发,改善总生存期。但也应该清醒地认识到,虽然系统治疗的进步已经深刻地改变了传统的外科治疗模式,但有关转化治疗、新辅助治疗和辅助治疗的临床研究大多为小样本Ⅱ期临床研究,高级别循证医学证据尚少。如何根据患者的肿瘤特点选择合理的治疗目标,从而确定个体化治疗方案,并寻找新的生物学标志物预测转化治疗及围手术治疗疗效,筛选真正获益人群,仍然需要进一步的探索。

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.