Insights into the 2023 multidisciplinary surgical treatment guidelines for hepatocellular carcinoma: perspectives from Italian Professional Associations

The collaboration among various Italian scientific societies to establish recommendations for the surgical management of hepatocellular carcinoma (HCC), recently published in Digestive and Liver Disease (1), is a worthy effort. This multidisciplinary approach, which includes input from different disciplines such as surgery, hepatology, gastroenterology, oncology, pathology, radiology, and patient associations, underscores the commitment to placing patients at the center of care. Such a holistic and inclusive approach enhances the relevance and applicability of these guidelines in clinical practice. While several scientific associations have previously issued guidelines for managing HCC, the Italian colleagues have adopted a comprehensive methodology. The development of key questions based on the Population, Intervention, Comparison, Outcomes (PICO) framework and the formulation of recommendations using the GRADE approach (2), followed by a voting process, reflects a rigorous and transparent procedure.

One of the significant strengths of these guidelines is the involvement of patient associations in their development. This is a pioneering step, especially in the technically complex field of surgical treatments. Including patients’ perspectives yields several advantages: (I) ensuring that the recommendations align closely with patient needs and preferences; (II) patients are more likely to adhere to guidelines they had a role in shaping, resulting in better treatment outcomes; (III) guidelines that consider patient input may have higher acceptance rates among diverse patient populations.

The guidelines address eight questions, some of which are pertinent, while others are already extensively covered in existing guidelines. For instance, the first question emphasizes the role of a multidisciplinary team (MDT) in optimizing HCC management. While having all recommended specialists in one MDT is ideal, it is often challenging due to resource and budget constraints, particularly in less affluent centers. A practical approach involves ensuring that at least three different specialists (a radiologist, a hepatologist and a surgeon) are present during the MDT, acknowledging the advisory role of MDT and the ultimate decision-making by the referring physician in consultation with the patient.

Holistic patient assessments, including roles for nurse coordinators and advanced practice nurses, are crucial. As highlighted in the work by Devictor et al. (3), nurse coordinators play a central role in managing HCC patients, though the role of advanced practice nurses is underreported. Multidisciplinary evaluations, rather than single-expert assessments, are recommended for diagnostic and therapeutic workups. High-activity centers with more than 75 HCC cases annually demonstrate better expertise, treatment access, and patient outcomes (3). However, geographic disparities in access to quality imaging and adequate treatment must be acknowledged (4) Adequate and adapted imaging is crucial for the accurate diagnosis and staging HCC, high-resolution imaging techniques, including quadriphasic imaging, being the minimum standard (5). When imaging is performed correctly, it can be effectively interpreted during MDT Board, in addition to clinical and biological information about the patient, to ensure comprehensive evaluation and optimal treatment planning.

The second question about the indication of hepatic resection versus thermal ablation for patients with Child-Pugh class A cirrhosis and single HCC aligns with previous guidelines. However, the expertise in radiological thermos-ablation in some centers, and the advancement achieved with this technique, might warrant consideration for thermal ablation even in larger tumors (6). The panel’s low evidence level for this recommendation indirectly reflects this nuance.

Question three addresses the indication of liver resection versus transarterial chemoembolization (TACE) in cirrhotic patients with good liver function and multinodular HCC. The vagueness of the question reflects the broader lack of consensus on defining multifocal HCC. Splitting this into separate questions for oligonodular/unilobar and multinodular/bilobar HCC could provide more precise guidance, particularly with emerging data from studies like the EMERALD 1 study (7). This study offers the possibility of optimal disease control and delaying tumor progression with durvalumab and bevacizumab when combined to TACE (7). It is not guaranteed to provide better results with resection in absence of a comparative trial. Currently, several trials are investigating the role for immune-checkpoint inhibitors combined with TACE, and even comparing them directly to TACE. The landscape of intermediate-stage HCC is likely to evolve soon. Furthermore, the expertise of the center will play a significant role in the outcomes. Here also the panel acknowledged the lack of evidence and graduate the evidence level as low.

The fourth question on liver resection versus sorafenib-based systemic therapy for HCC with intrahepatic macrovascular invasion seems outdated given advancements in systemic therapies, including immune checkpoint inhibitors, and loco-regional approaches such as radioembolization (8). Pre-operative approaches for some selected HCC patients may improve the results of resection in terms of tumor control, tumor downstaging and even survival (5,8). Notably, liver transplantation, that may be proposed of some selected patients (9), was not discussed in this guideline More current and innovative approaches should be considered in future guidelines.

For the fifth question, the panel’s use of a “Good Clinical Practice statement” rather than a formal recommendation is a prudent approach, reinforcing the need for flexibility in clinical judgment. Questions six, seven, and eight align closely with existing recommendations and offer less novelty.

Notably, the guidelines omit innovative topics such as minimally invasive surgery and the role of robotic platforms, which could significantly influence surgical practice in a near future (10-14).

In conclusion, these guidelines represent a substantial step forward in the multidisciplinary management of HCC in Italy. By incorporating diverse professional insights and patient perspectives, they provide a robust framework for optimizing patient outcomes. Future iterations could further enhance their relevance by addressing emerging surgical technologies and more nuanced clinical scenarios. The low to very low evidence of recommendation in these guidelines highlighted the lack of controlled randomized trial comparing surgery to other approaches for HCC patients in some setting.

It is likely the time to ask the right questions, as our Italian colleagues have done, and to support the need for such trials, despite the significant challenges in conducting them in our current era. These challenges include ethical considerations, the complexity of standardizing surgical techniques across multiple centers, the high costs and resource requirements, and the difficulty in recruiting a sufficiently large and diverse patient population to achieve statistically significant results.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, HepatoBiliary Surgery and Nutrition. The article did not undergo external peer review.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-24-373/coif). M.B. reports consulting fees and payment or honoraria from BMS, MSD, Roche, Eisai, AstraZeneca, Bayer, Sirtex Medical and Abbvie. The other 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.

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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