Published guidelines do not recommend radiotherapy as the standard treatment for any stage HCC, which limited its usage for this type of tumor1. Several decades ago, external radiotherapy was not recommended to treat patients with HCC because the radiation could not be precisely positioned according to tumor location, size, and shape, which might lead to the damage of normal liver tissue and surrounding vital organs, and liver failure. However, modern imaging techniques, including the emergent internal radiotherapy and stereotactic body radiotherapy (SBRT), as well as the progress in understanding the tolerance of liver parenchyma to radiation, led to the wide use of radiotherapy in the treatment of HCC as an adjuvant therapy[17, 18].
Several recent studies documented that HCC patients receiving radiotherapy combined with other treatments had longer survival than those treated with radiotherapy alone[19–21]. A meta-analysis that compared the efficacy of TACE combined with radiotherapy with TACE alone treatment in patients with portal vein tumor thrombus (PVTT) demonstrated that the combined treatment yielded a higher objective response rate (ORR) and better survival benefits than the TACE alone treatment. Wei and coworkers conducted a randomized clinical trial to compare the efficacy of hepatectomy combined with neoadjuvant radiotherapy with that of hepatectomy alone in patients with resectable HCC and portal vein tumor thrombus. The trial demonstrated that the 6, 12, 18, and 24 months OS and disease-free survival was significantly higher in the combined treatment group (P < 0.001). The present investigation compared the efficacy of the combination of liver resection and radiotherapy as the treatment for HCC with liver resection alone. Before PSM, the mOS and mCSS in the liver resection alone group were longer than in the combined treatment group (P < 0.05). However, the results documented that patients subjected to the combined treatment did not have better OS and CSS than patients treated with liver resection alone, after PSM.
Liver resection is recommended as the first-line treatment for early HCC by the EASL guideline, and it can increase the 1-, 3-, and 5-years survival1. However, liver resection can result in significant damage. Patients with HCC often present poor liver function and physical condition due to cirrhosis, which is one of the main reasons why liver resection is not widely used in HCC treatment. Although liver damage induced by radiotherapy has been markedly reduced, radiation-induced hepatotoxicity might trigger more extensive liver injury when combined with liver resection, leading to the death of patients due to liver failure.
A recent study by Lewandowski and collaborators concluded that radiotherapy could extend the survival of patients with early HCC. The results indicated that 90% of patients showed tumor response according to the EASL criteria, of which 59% showed a complete response with a median time to progression of 2.4 years and mOS of 6.7 years. Another analysis utilizing PSM compared the efficacy of radiotherapy and RFA in HCC patients with no more than three tumors, 3 cm or smaller in size. The results showed that the 3-year local recurrence rate in the radiotherapy group was lower than in the RFA group (P < 0.01), and the 3-year survival rate in the radiotherapy group was similar as in the with RFA group (P = 0.86). These findings indicate that in comparison with RFA, radiotherapy ensures superior local control and comparable OS. However, in the current study, mOS and mCSS of patients with AJCC stage I and II and with single tumor not larger than 5 cm, was comparable between the liver resection alone group and the combined treatment group. These results support the conclusion that radiotherapy may not provide additional survival benefits in HCC patients who received liver resection.
Although the mOS and mCSS in the liver resection alone group were longer than in the combined treatment group, in multivariate logistic regression analysis, the combination of liver resection and radiotherapy was an independent factor negatively affecting OS (P = 0.033), but not CSS (P = 0.216) before PSM. After PSM, the combined treatment did not predict the outcomes of patients.
Some limitations of the current study should be acknowledged. First, this research was designed as a retrospective analysis, and the selection bias was inevitable. However, the bias was reduced by employing the PSM model. Second, this study was population-based, liver function and physical condition of the patients were not consistently from the SEER data, and these factors might affect the patient outcomes. However, in contrast to previously published research, the present study included a large number of subjects, which strengthens the reliability of the results. Future randomized clinical trials are needed to confirm the results reported here.