PD-1 inhibitors combined with tyrosine kinase inhibitors for conversion therapy in patients with unresectable hepatocellular carcinoma: a retrospective cohort study

Introduction

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and a major cause of cancer-related mortality worldwide, particularly in regions such as Asia and China (1-3). In 2020, out of approximately 906,000 new liver cancer cases globally, East Asia had the highest proportion (26.9 per 100,000), with China accounting for 45.3% of global cases and 47.1% of global mortality (4,5). Although considerable progress has been made in the early diagnosis and treatment of this disease, most patients with HCC are diagnosed at an advanced or intermediate stage, at which point surgical resection is no longer a treatment option (6,7). As such, systemic therapy remains the primary treatment for managing advanced or unresectable HCC, although the prognosis of these patients remains extremely poor.

Conversion therapy, which involves the use of systemic or locoregional treatments to convert initially unresectable tumors into resectable ones, offers a potential option for improving patient survival (8,9). In recent years, there have been significant advances made in systemic therapies for patients with advanced HCC, particularly with the development of targeted therapies and immune checkpoint inhibitors. Tyrosine kinase inhibitors (TKIs) such as sorafenib and lenvatinib have become standard first-line treatments for unresectable HCC (10). TKIs primarily act by inhibiting tumor angiogenesis and cancer cell proliferation. Although they have shown efficacy in clinical trials, their objective response rates (ORRs) are still relatively modest, with lenvatinib yielding an ORR of 24.1% [95% confidence interval (CI): 19.5–29.1%] and sorafenib yielding an ORR of just 9.2% (95% CI: 6.2–13.0%) (11). Meanwhile, immune checkpoint inhibitors, particularly those targeting programmed cell death protein 1 (PD-1) and its ligand PD-L1, have revolutionized the treatment of several cancers, including HCC (12,13). PD-1 inhibitors work by restoring immune system function, allowing T cells to target and destroy cancer cells (14). When combined with other treatment modalities, PD-1 inhibitors have demonstrated enhanced efficacy in HCC (15,16). In the CARES-310 trial, compared to sorafenib in previously untreated patients with advanced HCC, a regimen consisting of camrelizumab plus apatinib significantly improved the ORR (25.4% vs. 6.7%), prolonged the median progression-free survival [PFS; 5.6 vs. 3.7 months; hazard ratio (HR): 0.56], and extended the median overall survival (OS; 22.1 vs. 15.2 months; HR: 0.62) (17).

Our study aimed to evaluate the real-world efficacy and safety of TKIs combined with PD-1 inhibitors as conversion therapy for patients with unresectable HCC. The primary outcome was the rate of successful conversion to resectability, and the secondary outcomes included the ORR, PFS, OS, and the safety profile of the treatment regimen. The results of this study can aid in the development of more refined patient selection criteria to identify individuals that benefit most from conversion therapy and optimize future treatment protocols. By assessing real-world data, our findings can provide a basis for clinical decision-making in the treatment of patients with HCC. We present this article in accordance with the STROBE reporting checklist (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-1-0023/rc) (18).

Methods

Study design and participants

A single-center, retrospective cohort study was conducted at a tertiary academic medical center. None of the included patients had previously participated in industry-sponsored clinical trials. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Xiangya Hospital, Central South University (No. 2026030594), and individual consent for this retrospective analysis was waived due to the retrospective nature of the study. Data were collected from patients treated at the Hepatobiliary and Pancreatic Surgery Department of Xiangya Hospital in Changsha, China between August 2018 and December 2023. Data collection and follow-up for all enrolled patients were conducted until the study cutoff date of July 30, 2024. A total of 63 patients with HCC were included in the study, all of whom received treatment with TKIs and PD-1 inhibitors, with some patients also receiving locoregional treatments.

The inclusion criteria were as follows:

• An age between 18 and 80 years.
• A clinical diagnosis of HCC [according to the 2022 Edition of Primary Liver Cancer Diagnosis and Treatment Guidelines ()] or histological confirmation of HCC.
• The presence of at least one indicator of unresectability, including a large tumor volume with an insufficient surgical margin (margin <1 cm) after evaluation or an inadequate volume of remaining liver after hepatectomy (in patients without cirrhosis and Child-Pugh A liver function: indocyanine green retention rate at 15 minutes (ICG-R15) <10% and ratio of future liver remnant volume to standard liver volume (FLR/SLV) <30%; in patients with chronic liver disease or liver parenchymal damage: FLR/SLV <40%; in patients with chronic liver disease and cirrhosis: ICG-R15 =10–20% and FLR/SLV <50%), the presence of large vessel invasion (portal vein, hepatic vein, and inferior vena cava) and the inability to undergo surgical reconstruction of vascular structures, the presence of extrahepatic metastasis, and unsuitability for surgical resection according to the multidisciplinary team (MDT) discussion;
• Eligibility for conversion therapy according to the China Liver Cancer criteria or presence of extrahepatic lymph node metastasis:
  • China Liver Cancer staging (CNLC) stage Ib–IIa: patients who cannot achieve R0 resection or cannot ensure a surgical margin (≥1 cm);
  • CNLC stage IIb–IIIa: patients whose tumors are confined to one hemiliver, or who have residual intrahepatic lesions ≤3 cm in diameter with potential curative intent; or patients deemed unsuitable for upfront surgery based on oncological considerations. This specifically includes patients with portal vein tumor thrombus (PVTT) type II–III as defined in the Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus (2021 edition) , or patients with hepatic vein or inferior vena cava tumor thrombus (HVTT/IVCTT) type I–II as defined in the Multidisciplinary Expert Consensus on the Diagnosis and Treatment of Hepatocellular Carcinoma with Hepatic Vein or Inferior Vena Cava Tumor Thrombus (2019 edition);
  • CNLC stage IIIb: patients with pulmonary oligometastasis (total metastasis ≤5 lesions, with a maximum diameter of each lesion ≤3 cm).
• Child-Pugh liver function classification A or B and Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2.
• At least one measurable target lesion [according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST)].
• No previous anticancer treatments.
• Informed consent and complete follow-up information.

Meanwhile, the exclusion criteria were as follows: (I) other malignant tumors; (II) other previous anticancer treatments; (III) severe organ dysfunction; (IV) uncontrolled severe comorbidities, including but not limited to poorly controlled severe infections, HIV-positive patients (HIV antibody positive), systemic diseases (such as neurological diseases, severe mental illness, epilepsy, or dementia, unstable or uncompensated respiratory, cardiovascular, renal diseases), active bleeding, or newly diagnosed thrombotic diseases while on therapeutic anticoagulation or with a bleeding tendency; (V) pregnant or breastfeeding women; (VI) Child-Pugh C liver function classification or ECOG PS >2; (VII) incomplete follow-up information; and (VIII) allergy to the treatment drugs or poor treatment adherence.

Procedure

The treatment regimen for enrolled patients included TKIs (apatinib or lenvatinib) combined with PD-1 inhibitors (such as camrelizumab, sintilimab, toripalimab, pembrolizumab, and envafolimab). A portion of the patients also received sequential locoregional treatments [such as transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), and stereotactic body radiotherapy (SBRT)]. In cases of treatment-related adverse events, symptomatic supportive therapy or appropriate management according to the drug’s instructions was provided.

The administration of targeted drugs was as follows: lenvatinib was administered at 8 mg for body weight <60 kg taken orally once daily or at 12 mg for body weight ≥60 kg taken orally once daily. Apatinib was administered at 250 mg taken orally once daily. Immunotherapy drugs included camrelizumab (200 mg), sintilimab (200 mg), toripalimab (200 mg), and pembrolizumab (200 mg), all administered intravenously every 3 weeks. Envafolimab (200 mg/vial) was injected subcutaneously in each arm (one vial per arm) every 3 weeks.

TACE and HAIC treatments were performed by the Department of Interventional Radiology. For TACE treatment, a catheter was selectively inserted into the hepatic artery for digital subtraction angiography imaging to identify the tumor’s location and size. A microcatheter was then superselectively inserted into the tumor’s blood supply artery. Based on the tumor staining results, the decision was made whether to use iodine oil injection, drug-loaded microspheres, or doxorubicin hydrochloride to embolize the tumor’s feeding artery.

For HAIC treatment, the FOLFOX [folinic acid (leucovorin), 5-fluorouracil, and oxaliplatin] regimen was typically used. The treatment was administered through a femoral artery puncture, with the microcatheter superselectively inserted into the tumor’s blood supply artery and left in place. The FOLFOX regimen included oxaliplatin (85 mg/m²), leucovorin (400 mg/m²), and 5-fluorouracil (400 mg/m² bolus and 2,400 mg/m² continuous infusion for 46 hours). SBRT was carried out by the Department of Radiation Oncology at our hospital. Based on the patient’s condition, lesion location, number, size, and other factors, an optimal radiotherapy plan was developed in collaboration with medical specialists.

Follow‑up and assessments

Standardized patient evaluations were performed prior to each treatment session or during routine follow-up visits at intervals of at least 3–4 weeks. Tumor response was assessed on all follow-up cross-sectional computed tomography or magnetic resonance imaging scans, according to the mRECIST. Two independent radiologists with over 5 years of experience conducted the evaluations. In the event of discrepancies, the final decision was made by the senior radiologist. All radiologists involved in this study received both lecture-based and online training to ensure consistency in tumor response assessment.

Safety monitoring was carried out continuously through routine laboratory tests and the monitoring of vital signs. Adverse events were classified as treatment-emergent and graded at the time of occurrence. This approach was uniformly applied across all participating centers. The severity of adverse events was evaluated in accordance with the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. All patients were followed up regularly until death or the conclusion of the study in December 2024.

Outcomes

The primary outcome measure was the rate of successful conversion as evaluated by the investigators. Secondary outcome measures included OS, PFS, ORR, and safety. PFS was defined as the time from the date of enrollment in both groups to the date of disease progression or death from any cause. ORR was defined as the proportion of patients who achieved a partial (PR) or complete response (CR) to treatment, as per the mRECIST. The enrollment time was defined as the date when PD-1 inhibitor therapy was initiated.

Bias

To minimize selection bias, we included all consecutive patients who met the eligibility criteria within the defined study period. To address potential information bias from subjective tumor assessment, two independent radiologists, blinded to clinical outcomes, evaluated all imaging scans according to the mRECIST. Any discrepancies in the assessment were resolved by a third, senior radiologist.

Study size

The study size was determined according to the number of eligible patients who received the specified conversion therapy regimen at our center during the defined study period. A formal a priori sample size calculation was not performed, as this was a retrospective, exploratory analysis of all available cases.

Statistical analysis

Data are presented as the median value with the interquartile range (IQR) or 95% CI or as the frequency (%). Continuous variables were compared via the Student’s t-test or the nonparametric Wilcoxon signed-rank test, as appropriate. Categorical variables were analyzed with the χ² test or the Fisher exact test. Univariate Cox regression analyses were employed to assess the associations between risk factors and survival. Kaplan-Meier survival curves were generated to visualize survival outcomes, with differences between the curves compared with the log-rank test. All statistical analyses were performed with R software version 4.4.1 (The R Foundation for Statistical Computing, Vienna, Austria).

Results

Patient selection

A total of 155 patients diagnosed with unresectable liver cancer were initially enrolled in this study. The patient selection process is detailed in Figure 1. Patients were excluded based on the following criteria: receipt of other antitumor therapies prior to treatment (n=14), poor treatment compliance or incomplete follow-up information (n=41), diagnosis with other concurrent malignant tumors (n=2), and extremely poor general condition (n=1). Furthermore, 34 patients were excluded as they were deemed not eligible for conversion therapy. Consequently, 63 patients who were suitable for conversion therapy were ultimately included in the final analysis (Figure 1).

Figure 1 Flowchart of patient inclusion.

Patient characteristics

The study included 63 patients with HCC who were treated with a combination of PD-1 inhibitors and TKIs (Table 1). The majority of patients were younger than 60 years (n=44, 69.8%), with 30.2% (n=19) being 60 years or older, and most were male (n=56, 88.9%). In terms of performance status, 92.1% (n=58) had an ECOG score of 0, while 7.9% (n=5) had a score of 1. The Child-Pugh classification was A in 85.7% (n=54) of patients and B in 14.3% (n=9). According to the Barcelona Clinic Liver Cancer (BCLC) staging system, 25.4% (n=16) were classified as stage A, 23.8% (n=15) as stage B, and 50.8% (n=32) as stage C. Based on the CNLC staging system, patients were distributed across stages Ib (n=9, 14.3%), IIa (n=9, 14.3%), IIb (n=13, 20.6%), IIIa (n=26, 41.3%), and IIIb (n=6, 9.5%). Extrahepatic spread was present in 9.5% (n=6) of patients, while 90.5% (n=57) showed no evidence of extrahepatic spread. Alpha-fetoprotein (AFP) levels were below 400 ng/mL in 55.6% (n=35) of patients and 400 ng/mL or higher in 44.4% (n=28). Hepatitis B virus (HBV) infection was present in 84.1% (n=53) of patients, with 15.9% (n=10) being HBV negative. Local therapy for HCC had been administered to 41.3% (n=26) of patients, while 58.7% (n=37) had not received local therapy (Table 1).

Treatment

In this study, the PD-1 inhibitors used included envafolimab, camrelizumab, pembrolizumab, tislelizumab, and sintilimab. The median duration of immunotherapy maintenance was 12 months (IQR 6–19). The TKIs employed were apatinib and lenvatinib, with a median duration of targeted therapy maintenance of 9 months (IQR 4.5–14). Local treatment was combined in 26 patients (41.3%), including 14 (22.2%) cases of TACE, 3 (4.8%) cases of HAIC, 5 (7.9%) cases of SBRT, and 4 (6.3%) cases of combined TACE and HAIC.

Tumor response

According to mRECIST, 7 (11.1%) patients achieved a CR, 45 (71.4%) had a PR, 9 (14.3%) showed stable disease (SD), and 2 (3.2%) experienced progressive disease (PD). According to RECIST 1.1, no patients achieved CR, 40 (63.5%) had PR, 19 (30.2%) showed SD, and 4 (6.3%) had PD. The mRECIST identified more patients with CR and PR than did RECIST 1.1, while RECIST 1.1 indicated more cases of SD and PD (Table 2). Waterfall plots of the greatest percentage change in target-lesion size from baseline according to mRECIST and RECIST 1.1 are presented in Figure 2 and Figure 3, respectively.

Figure 2 Waterfall plot of the greatest percentage change in target-lesion size from baseline according to mRECIST. PD, progressive disease; PR, partial response; mRECIST, modified Response Evaluation Criteria in Solid Tumors; SD, stable disease.

Figure 3 Waterfall plot of the greatest percentage change in target-lesion size from baseline according to RECIST 1.1. PD, progressive disease; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease.

Surgical resection of tumors

Among the 63 patients analyzed, the overall conversion success rate was 60.3% (38/63). When stratified by CNLC stage, the conversion success rates were 66.7% (6/9) for Stage Ib, 88.9% (8/9) for Stage IIa, 30.8% (4/13) for Stage IIb, 65.4% (17/26) for Stage IIIa, and 50.0% (3/6) for Stage IIIb. Among these patients, 11 refused surgery and continued with the original treatment plan. Of the 27 patients who underwent conversion surgery, 21 received liver resection, while 6 underwent curative microwave ablation surgery. Postoperative pathological evaluation revealed that 7 (33.3% of the 21 patients who underwent liver resection) patients achieved pathological complete response (pCR), and 3 (14.3%) patients achieved major pathological response.

Survival

As of December 2024, the median follow-up time was 20.9 months (95% CI: 20.7–28.2). The median PFS for the overall cohort was 20.7 months (95% CI: 15.6–not reached) (Figure 4), and the median OS was not reached (Figure 5). Among patients who achieved successful conversion therapy, the median PFS was significantly prolonged at 41.23 months (95% CI: 40.6–not reached), while the median OS was not reached. In contrast, patients who failed conversion therapy had a median PFS of 12.8 months (95% CI: 9.13–15.87) and a median OS of 20.3 months (95% CI: 19.13–not reached). Successful conversion therapy was identified as an independent favorable prognostic factor for both PFS and OS (Table 3). Compared to conversion failure, successful conversion was associated with a significantly reduced risk of disease progression (HR: 0.11, 95% CI: 0.04–0.33; P<0.001) (Figure 6) and death (HR: 0.10, 95% CI: 0.03–0.31; P<0.001) (Figure 7).

Figure 4 Kaplan-Meier analysis of progression-free survival in the overall population.

Figure 5 Kaplan-Meier analysis of overall survival in the overall population.

Figure 6 Kaplan-Meier analysis of progression-free survival among patients with conversion success and those with conversion failure.

Figure 7 Kaplan-Meier analysis of overall survival among patients with conversion success and those with conversion failure.

Safety

In the study, 30.2% (n=19) of patients experienced grade 3 or 4 adverse events. The most common adverse events included increased transaminase levels (n=19, 30.2%), leukopenia (n=11, 17.5%), reactive cutaneous capillary endothelial proliferation (n=9, 14.3%), elevated total bilirubin (n=9, 14.3%), skin lesions (n=9, 14.3%), fatigue (n=8, 12.7%), hand-foot syndrome (n=7, 11.1%), hypothyroidism (n=6, 9.5%), diarrhea (n=6, 9.5%), nausea and vomiting (n=6, 9.5%), hypertension (n=5, 7.9%), and abdominal pain (n=5, 7.9%). Other adverse events, each occurring in fewer than 5% of patients, included proteinuria, thrombocytopenia, gastrointestinal bleeding, headache, arthralgia, fever, stomatitis and nasal mucositis, gingival bleeding, alopecia, diabetes, myalgia, and encephalitis (Table 4).

Discussion

This retrospective study demonstrated that while the combination of TKIs and PD-1 inhibitors provides a tolerable and effective backbone for conversion therapy in unresectable intermediate and advanced HCC, the primary driver of prolonged OS and potential PFS is the successful transition to surgical resection. Conversion therapy offers the possibility of tumor-free survival and prolonged OS for patients with advanced cancer. However, this field is relatively new, and controversies regarding its target population, treatment regimens, and postoperative management persist (19-21). Although preliminary studies on HCC conversion therapy have been conducted, its widespread application is limited due to the lack of high-quality evidence and universally accepted standard treatment protocols (22). The core of conversion therapy consists of transforming unresectable HCC into a resectable state through systemic therapy. Our treatment philosophy emphasizes targeted therapy first and local therapy as a follow-up, prioritizing systemic treatment with targeted therapies (e.g., lenvatinib) combined with immune checkpoint inhibitors (e.g., PD-1 inhibitors), followed by local therapies (e.g., interventional therapy) as needed (23). However, not all patients require a “triple” regimen (targeted + immune + local therapy) from the outset. Repeated local interventional treatments may significantly reduce liver function and increase the difficulty of subsequent surgeries. Therefore, treatment plans should be individualized, with liver function, tumor burden, and treatment response being taken into account.

In this study, according to the mRECIST, the ORR for TKIs combined with anti-PD-1 therapy was 82.5% (52/63), while according to RECIST 1.1, it was 63.5% (40/63); these were higher than the 40.8% (mRECIST) and 26.1% (RECIST 1.1) reported in the LEAP-002 trial, respectively (24). This discrepancy may be due to the application of local therapies and the proportion of HBV-related HCC. The majority of patients in our study had HBV-related HCC (84.1%), while only 48.6% of patients in the LEAP-002 trial had HBV-related HCC (24). Lenvatinib, the TKI used in our study, has shown stronger activity in HBV-related HCC. Additionally, a recent meta-analysis indicated that patients with HBV- or HCV-related HCC benefit more from immune checkpoint inhibitors (25).

In this study, the conversion success rate was 60.3% (38/63), the conversion resection rate was 33.3% (21/63), and the pCR rate was 11.1% (7/63). These results are superior to those reported in a retrospective study on TKI combined with anti-PD-1 therapy in a similar population (conversion success rate, 19.1%; actual surgery rate, 15.9%; and pCR rate, 9.5%) (26). This discrepancy may be attributed to our meticulous patient selection strategy. Unlike the BCLC and NCCN guidelines, which generally regard extrahepatic spread or major vascular invasion as non-curable disease, the CNLC staging system emphasizes a more proactive, conversion-oriented treatment strategy. It recognizes that selected patients who are technically unresectable, with limited vascular invasion or oligometastatic disease, may still achieve curative-intent resection after effective systemic downstaging. In contrast to broader inclusion approaches, we established more precise inclusion criteria in real-world clinical practice based on the CNLC staging system. For instance, for patients with CNLC stage Ib–IIa, we included only those unable to achieve R0 resection or those for whom a surgical margin of ≥1 cm could not be guaranteed, ensuring that conversion therapy targeted a subgroup with potential for downstaging. Similarly, for patients with CNLC stage IIb–IIIb, we selected patients with tumors confined to half the liver or residual lesions ≤3 cm amenable to ablation, optimizing the likelihood of achieving a curative outcome. For patients with CNLC stage IIb–IIIa, our focus on patients with specific vascular involvement—such as those with PVTT type II–III or HVTT/IVCTT type I–II, as defined by established guidelines—allowed us to identify those who, despite being initially unresectable, could benefit from aggressive systemic therapy to enable surgery. Additionally, for patients with CNLC stage IIIb, the inclusion of patients with limited extrahepatic disease (e.g., pulmonary oligometastasis with ≤5 lesions, each ≤3 cm, or lymph node metastasis) ensured that metastatic burden remained manageable, potentially enhancing conversion feasibility. These carefully delineated criteria likely contributed to our cohort containing patients more responsive to PD-1 inhibitors and TKIs, thereby improving conversion and resection rates. Furthermore, differences in surgical resection criteria—such as our emphasis on achieving oncologically meaningful outcomes rather than solely technical resectability—may have contributed to the higher pCR rate observed. Collectively, this precision in patient selection and surgical decision-making underscores the importance of individualized treatment strategies in optimizing outcomes for unresectable HCC. Identifying the target population for conversion therapy is of considerable clinical significance. Patients with indicators of good therapeutic response (e.g., relatively limited tumor burden, good liver function, and suitable systemic condition) are more likely to achieve surgical opportunities and long-term survival after conversion therapy (27). Therefore, screening suitable patients for conversion therapy and encouraging active treatment is key to improving efficacy. Through precise patient stratification, resource allocation can be optimized, and overtreatment of patients unsuited to this type of therapy can be avoided. It is worth noting that the addition of local therapy inevitably increases costs, trauma, side effects, and complicates the assessment of drug efficacy. Compared to that in previous studies, the survival benefit of the conversion therapy regimen in our study was satisfactory. The median PFS was 20.7 months for the overall cohort, which was significantly extended to 41.23 months for patients with successful conversion, and the median OS exceeded 5 years. In contrast, patients with failed conversion had a median PFS of 12.8 months and a median OS of 20.3 months. These data collectively demonstrate the efficacy of this conversion therapy regimen and the critical role of successful conversion in achieving surgical benefit. This phenomenon is best understood when viewed alongside the landmark results of recent Phase III trials. The divergent outcomes of COSMIC-312 and CARES-310 underscore the critical roles of etiology and drug synergy in HCC (17,28). The success of CARES-310, which achieved a record-breaking median OS of 23.8 months, is largely attributed to its HBV-dominant Asian cohort, which is highly responsive to PD-1/VEGFR inhibition. Conversely, COSMIC-312 failed to show OS benefit, likely due to a higher proportion of non-viral HCC and the prohibitive toxicity of cabozantinib (28). While CARES-310 trials define the upper limits of systemic therapy alone, our findings suggest that utilizing such high-response regimens as a “bridge” to surgery can transcend the existing survival ceiling. The conversion therapy regimen used in this study was generally well-tolerated, with manageable adverse events and no new or unexpected toxicities. The incidence of any grade of adverse events was lower than that reported in similar studies (26), possibly due to the retrospective nature of the design, and some adverse events might not have been promptly followed up on.

A key limitation of this study is that the survival benefits are driven by surgical intervention following successful downstaging, meaning the results reflect the efficacy of the entire conversion-to-surgery pathway rather than the isolated impact of the TKI plus PD-1 combination. Additionally, the lack of a concurrent control group makes it difficult to definitively attribute the observed outcomes solely to the intervention. Furthermore, as the study was conducted at a single center in China with a predominantly HBV-related HCC population, the generalizability of these findings to other populations with different HCC etiologies or in different healthcare settings may be limited. Future multicenter, large-sample, randomized controlled studies are needed to further validate the efficacy of conversion therapy and identify optimal treatment strategies.

Conclusions

TKIs combined with PD-1 inhibitors demonstrated good efficacy and safety in conversion therapy for unresectable patients with intermediate-to-advanced HCC. Radical surgery after successful conversion significantly prolonged PFS and should be recommended as a standard treatment strategy. Future research should further optimize the patient selection criteria, treatment strategies, and postoperative management to enhance the overall efficacy of conversion therapy.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-1-0023/rc

Data Sharing Statement: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-1-0023/dss

Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-1-0023/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2026-1-0023/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Xiangya Hospital, Central South University (No. 2026030594), and individual consent for this retrospective analysis was waived due to the retrospective nature of the study.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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(English Language Editor: J. Gray)