Gaps and challenges of available clinical guidelines on treatment options for early hepatocellular carcinoma

Dear Editor, Hepatocellular carcinoma is one of the cancers with a rising prevalence and incidence globally, making it a priority for research and public health intervention according to global cancer agendas[1]. Early detection of this cancer is essential to improve disease-free survival rates and healthy lifespan[1]. To establish an evidence-based, comprehensive care pathway, available clinical practice guidelines provide valuable recommendations. However, these guidelines must consider a broad range of factors to ensure that their recommendations have adequate external validity in real-world settings. Wu et al.[2] recently published a bibliometric evaluation and analysis of clinical practice guidelines for the treatment of hepatocellular carcinoma (HCC). The authors have undertaken a valuable and novel task by examining the evolution and methodological quality of the published guidelines, highlighting the increasing role of radiofrequency ablation (RFA) and surgical resection in the management of early-stage HCC[2]. However, we believe there are important aspects that warrant further reflection, as well as the identification of gaps and opportunities for improving the development of future guidelines. Despite the robust evaluation using the AGREE-II tool (Appraisal of Guidelines for Research & Evaluation II), it is notable that many guidelines suffer from limited stakeholder engagement. This is reflected in the relatively low scores in the domain of stakeholder involvement, which could affect the applicability and relevance of the recommendations[3]. For guidelines to be truly patient-centered, it is essential to involve not only clinical experts but also patients, caregivers, and professionals from various disciplines related to the care of HCC. Along these lines, future guidelines should incorporate structured consensus methods that integrate multiple perspectives, thereby optimizing clinical applicability[4]. These concepts align with the innovative approach of evidence-based research, which seeks to enhance the quality, relevance, and significance of medical research[5]. Furthermore, the variability observed in recommendations across different regions raises questions about the consistency in assessing the level of evidence. While the inclusion of guidelines from diverse regions is a commendable effort, differences in the interpretation of the level of evidence (such as the use of GRADE [Grading of Recommendations Assessment, Development and Evaluation] versus other systems) suggest the need for clearer, universal standards for evaluating the quality of underlying studies[6]. Additionally, it was notable that there were no guideline-developing groups in Africa or Latin America, highlighting a significant gap in the availability of evidence in these regions. This lack hinders evidence-based decision-making adapted to specific contexts, particularly in resource-limited settings[7]. A key recommendation emerging from the authors’ conclusions was the need to develop high-quality comparative studies that directly assess the effectiveness of RFA versus surgical resection. However, the methodological and ethical challenges of conducting randomized clinical trials in this area have limited the availability of robust data. To address this issue, we propose exploring innovative approaches, such as pragmatic implementation studies and the use of electronic health records[8], to generate real-world evidence that complements traditional clinical trials. This approach would capture the variability of daily clinical practices and, in turn, facilitate the generalization of results[8]. Another area that warrants attention is the incorporation of emerging technologies, such as navigation-assisted ablation and minimally invasive surgical techniques, which could redefine the treatment paradigm for patients with early-stage HCC[9]. However, the adoption of these technological innovations requires guidelines that not only evaluate their efficacy but also consider cost-effectiveness, accessibility, and learning curve, particularly in resource-limited regions. Finally, one of the most significant findings of this analysis was the heterogeneity in the implementation of recommendations, influenced by differences in healthcare infrastructure and regional resources. This highlights the need to develop guidelines that, while based on the best scientific evidence, are also adaptable to local contexts, enabling healthcare professionals to make informed decisions that are realistic for their practice environments[10]. This is where approaches such as “living guidelines,” which allow for continuous updates and regional adaptations, could provide a viable solution to maintaining the relevance and applicability of the guidelines[11]. In conclusion, there is an urgent need to move towards more comprehensive and adaptable recommendations that reflect both the best scientific evidence and the realities of clinical practice across diverse regions. We propose that future efforts focus on increasing stakeholder engagement, improving methodological standardization, and exploring new ways to generate and implement evidence, thereby offering more precise and patient-centered management.