Editor's Note: On August 22, 2026, the phase III TALENTOP study, led by Academician Jia Fan and conducted across 24 centers nationwide, was published in The Lancet, a leading international medical journal. The study provides high-level Chinese clinical evidence for conversion therapy in advanced hepatocellular carcinoma (HCC) and redefines the boundaries of surgical treatment for advanced HCC. These findings have attracted widespread academic attention in China and internationally.To explore the TALENTOP study’s design rationale, efficacy benefits, surgical implementation, safety management, and real-world clinical value in depth, Oncology Frontier has launched the special series “Transformation Breakthroughs.” We have invited principal investigators (PIs) involved in the multicenter TALENTOP study to share their frontline research experience and translate high-level clinical evidence into practical insights for clinicians in China. The series aims to help colleagues understand both the opportunities and limitations of conversion therapy for advanced HCC and jointly advance its standardized implementation nationwide.
When systemic therapy is combined with hepatectomy, clinicians are understandably concerned about the cumulative toxicity burden. TALENTOP provides one of the most comprehensive safety datasets available to date for conversion therapy, systematically characterizing the adverse-event profile, perioperative complications, and immune-related toxicities associated with combining targeted therapy and immunotherapy with surgery. A detailed interpretation of these data is clinically important for developing toxicity-management strategies spanning induction treatment, the perioperative period, and postoperative maintenance, thereby maximizing the benefits of conversion therapy while safeguarding patient safety.
For the fourth installment of this series, we invited Professor Jie Gao of Peking University People’s Hospital, Professor Deyu Li of Henan Provincial People’s Hospital, and Professor Xinyu Bi of the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, to discuss toxicity and comprehensive management of immunotherapy combined with surgery from the perspective of TALENTOP, highlighting the key principles of safety in conversion therapy.
The Overall Safety Profile
TALENTOP Confirms That Adverse Events Were Generally Manageable in Both Groups
Oncology Frontier: Surgical intervention increases overall treatment exposure and intensity. It is therefore important to compare adverse-event profiles between patients receiving surgery plus systemic therapy and those receiving systemic therapy alone. Based on the TALENTOP data, could you describe the overall adverse-event profiles in the two groups? What similarities and differences were observed between the surgery-plus-maintenance group and the systemic-therapy-only group?
Professor Jie Gao: According to TALENTOP, adverse events (AEs) of any grade occurred in 88% of patients in the surgery group and 93% in the systemic-therapy-only group. The overall incidence of AEs of any grade was therefore similar between the two groups. This suggests that adding surgery did not substantially increase the burden of lower-grade adverse events.
However, the difference was more pronounced for high-grade events. Grade 3–5 treatment-related adverse events (TRAEs), including two treatment-related deaths, occurred in 41% of patients in Group A and 21% in Group B. When restricted to grade 3–4 events, the incidence in Group A was 39%. Serious TRAEs occurred in 23% of patients in Group A, compared with 7% in Group B.
These findings indicate that adding surgery increased the incidence of high-grade and serious TRAEs. This reminds us that treatment intensity and the risk of serious toxicity rise when surgery is incorporated into the treatment strategy, although the overall safety profile remains manageable.
In clinical practice, we must acknowledge the toxicity challenges associated with adding surgery while also recognizing that the overall risks can be managed. With enhanced monitoring throughout the treatment course, individualized risk assessments, and emergency management plans established and implemented in advance, we can identify and intervene in adverse events early and help patients navigate the perioperative period safely. This is essential to realizing the long-term survival benefits of conversion therapy.
Perioperative Management
The Study Confirms the Safety and Feasibility of Conversion Hepatectomy at Experienced Centers
Oncology Frontier: Perioperative complications are a major concern when implementing conversion therapy. Clinicians are particularly concerned about bleeding, impaired wound healing, and serious surgical complications. Could you describe the incidence of surgery-related adverse events and high-grade surgical complications during the perioperative period in TALENTOP?
Professor Deyu Li: The surgery-related safety data from TALENTOP further support the conclusion that perioperative risks associated with conversion hepatectomy are generally manageable when the procedure is performed at experienced centers.
Specifically, the incidence of serious surgery-related TRAEs was 12%, with postoperative wound infection being the most common event, occurring in 2% of patients. Regarding high-grade complications, the incidence of severe surgical complications of Clavien–Dindo grade III or higher was 16% (13/83). These included common serious postoperative complications such as bleeding, bile leakage, and intra-abdominal infection. Such events can be managed promptly through standardized perioperative care.
Importantly, the study did not identify any unexpected surgery-related safety signals beyond those anticipated. This suggests that adding hepatectomy to targeted therapy plus immunotherapy does not necessarily introduce uncontrollable additional risks.
A key reason is the treatment strategy used in the study: patients received three cycles of atezolizumab plus bevacizumab (T+A), followed by atezolizumab alone in cycle four. This allowed time for the antiangiogenic agent to wash out, creating a safer window for surgery. Strict patient selection and standardized procedures across participating centers also helped ensure surgical safety.
Reversible Toxicity
Treatment Interruption and Resumption Data Highlight the Clinical Manageability of Toxicity
Oncology Frontier: Whether toxicity leads to treatment interruption or permanent discontinuation directly affects the clinical practicality of a treatment strategy and is an important indicator of whether toxicity is manageable. Could you discuss the rates of treatment discontinuation due to AEs and treatment resumption after temporary interruption in the two TALENTOP groups? What do these findings tell us about the reversibility of toxicity with this approach?
Professor Xinyu Bi: From a surgeon’s perspective, our concerns about the safety of conversion therapy center on two main issues. First, will toxicity force treatment discontinuation? Once treatment is stopped, conversion therapy cannot continue as planned, potentially substantially reducing the likelihood of successful conversion. Second, will treatment-related toxicity increase surgical risks and the incidence of postoperative complications?
TALENTOP showed that 25% of patients in both the surgery group and the control group permanently discontinued treatment because of AEs. This suggests that adding surgery did not increase the risk of permanent discontinuation of systemic therapy.
In addition, treatment was resumed after a temporary interruption in 25% of patients in the surgery group and 22% in the control group. These findings indicate that treatment can be resumed in many cases after a temporary interruption and appropriate symptomatic management of treatment-related toxicities. This is particularly important for enabling patients to continue receiving conversion therapy.
Nevertheless, we must remain vigilant. During conversion therapy, especially in patients who respond sufficiently to become eligible for surgical resection, close monitoring for treatment-related liver injury is essential. Preoperative hepatic functional reserve must be rigorously assessed, and the risk of postoperative hepatic insufficiency must be carefully evaluated. These measures help optimize patient selection and ensure the safety of surgery following conversion therapy.
Comprehensive Management Throughout the Treatment Course
Establishing an Integrated irAE Management Strategy to Support Long-Term Survival
Oncology Frontier: Immune-related adverse events (irAEs) can be subtle in presentation and delayed in onset. In conversion therapy, a management strategy covering induction treatment, the perioperative period, and postoperative maintenance is therefore essential. Across the full conversion-treatment pathway represented by TALENTOP, how should irAEs be identified, graded, and managed? What key monitoring measures should be implemented during postoperative maintenance?
Professor Xinyu Bi: Our center participated extensively in the TALENTOP study. In clinical practice, atezolizumab plus bevacizumab (T+A) is also one of our frequently used treatment options and is widely applied in both first-line treatment of advanced disease and conversion therapy. We are currently conducting clinical studies of T+A in the neoadjuvant setting as well. Overall, the safety profile of T+A is manageable, and we have accumulated substantial experience in managing irAEs.
Our guiding principle in irAE management is always early recognition and early intervention. Whenever immune-mediated injury is suspected, appropriate treatment, including corticosteroids, should be initiated promptly. Complex cases require multidisciplinary collaboration. We typically invite specialists from medical oncology and hepatology to participate in discussions and develop the optimal management strategy. Our key lesson is that when early signs of an irAE emerge, clinicians should not hesitate to initiate corticosteroids or other appropriate interventions promptly.
During the perioperative period, we focus on monitoring liver function, coagulation parameters, and surgical wound healing, while also assessing the risk of bleeding associated with antiangiogenic therapy.
TALENTOP showed that postoperative maintenance therapy can provide significant survival benefits in patients who successfully undergo conversion therapy. Therefore, maintenance treatment is crucial to prolonging survival. During this phase, continued monitoring of liver function, proteinuria, thyroid function, and other relevant parameters is necessary to address the toxicities associated with both immunotherapy and bevacizumab.
It is equally important to establish a routine follow-up mechanism involving both surgical and medical oncology teams. These teams must dynamically assess when to continue maintenance therapy, temporarily suspend it, or discontinue systemic treatment altogether. The ultimate goal is to prolong survival while preserving patients’ quality of life.
Conclusion
The safety data from TALENTOP provide a robust evidence base for the safe implementation of conversion therapy. From the overall comparison of adverse-event profiles between the two groups, to the manageability of perioperative complications, the evidence of toxicity reversibility, and the establishment of comprehensive management strategies, the study sets an important benchmark for the safety management of immunotherapy combined with surgery in advanced HCC.
Maintaining the safety threshold is essential for sustainable progress. These findings translate into practical clinical guidance: strengthen monitoring, prepare management plans in advance, and ensure early recognition and intervention. With appropriate safety measures in place, conversion therapy can deliver meaningful benefits to patients.
Coming Next: In the fifth installment of this series, we will continue to explore the real-world value of the TALENTOP study and pathways for translating its findings into clinical practice. Stay tuned.
Professor Xinyu Bi
Professor Deyu Li
Professor Jie Gao
