DISCUSSION
platelet decrease, deaths, HCC, BCLC
HEPATITIS B, VIRUS, RECURRENT CANCER, HEPATITIS C
This prospective study demonstrated that RFA combined with anti‐PD‐1 prolonged median RFS by 87.8% or 7.2 months compared to RFA alone in patients with recurrent cancer while showing the same effect in a subgroup analysis. In both univariate and multivariate analyses, the choice of treatment was identified as an independent risk factor for prognosis. Additionally, both the combination of RFA and anti‐PD‐1 and RFA alone showed an acceptable safety profile. Greten et al. reported a surprising response to topical therapy in combination with anti‐PD‐1,Anti‐PD‐1 immunotherapy has exhibited good therapeutic effects in the treatment of advanced HCC. However, the efficiency of anti‐PD‐1 monotherapy is still unsatisfactory, and increasing the proportion of beneficiaries is currently a hot issue.Furthermore, this study was conducted with a short‐term dosing period of only 3 months. Additionally, all patients completed four cycles of anti‐PD‐1 treatment. Studies have shown significant advances in immunotherapy for HCC,Our study similarly found that the combination of RFA and anti‐PD‐1 treatment was more effective in patients with advanced HCC. Among our enrolled patients, there was also a patient with stage C BCLC who chose to be treated with RFA combined with anti‐PD‐1 after relapse of previous treatment. This patient experienced significantly prolonged RFS, maintained grade A liver function, and did not experience any irAEs. The conclusion of our research aligns with previously reported findings, which have shown that anti‐PD‐1 alone or in combination with other therapies demonstrates promising antitumor effects in advanced HCC. Previously treated patients with advanced HCC showed an overall response rate (ORR) of 18.8% with anti‐PD‐1 monotherapy.In our study, the results of the subgroup analysis showed that patients below the age of 60 benefited more from combination therapy compared to patients aged 60 and above. This difference in response may be related to alterations in the immune system, as suggested by Fane and Weeraratna.In addition to its promising efficacy, RFA combined with anti‐PD‐1 has also proven to be safe. No treatment‐related deaths have been reported in this study. All grades of AEs associated with RFA in this study were leukocyte decrease, neutrophil decrease, and platelet decrease, which is consistent with previous findings.While discussing our findings, it is important to consider the limitations of our research. Firstly, the relatively small sample size of this study should be interpreted with caution. Our subgroup analysis found that male patients had a more favorable prognosis than female patients after receiving RFA combined with anti‐PD‐1 therapy, but this observation needs to be further confirmed in larger controlled trials. Secondly, the short follow‐up period did not allow for an assessment of overall survival, and further analysis is needed to evaluate the associated prognosis. Thirdly, this was a non‐randomized observational study, which introduces potential selection and ascertainment bias, despite efforts to balance baseline information. Additionally, the majority of patients enrolled in this study were infected with the hepatitis B virus, so further research is necessary to confirm these findings in other patient groups, including those with the hepatitis C virus.In general, the findings indicate that combining RFA with anti‐PD‐1 therapy is a safe and effective treatment option for individuals experiencing recurrent HCC. It leads to a significant improvement in RFS and has an acceptable safety profile compared to using RFA alone. However, further investigations are necessary to determine the optimal timing and duration of RFA combined with anti‐PD‐1 therapy, as this remains controversial in reported clinical trials. Our results still require large sample, randomized, controlled clinical trials to validate and address relevant issues in the future.