Efficacy of Acupuncture Combined with the Three-Step Analgesic Protocol in Treating Pain in Liver Cancer Pain: A Bayesian Network Meta-Analysis

This Bayesian meta-analysis represents the first systematic study to compare different acupuncture modalities combined with the WHO three-step analgesic protocol for the treatment of liver cancer pain. The study included 27 randomized clinical trials involving 2,220 patients, covering six different acupuncture modalities: acupoint herbal application, acupoint injection, acupuncture with moxibustion, simple acupuncture, heat-sensitive moxibustion, and floating needling. The clinical context is significant given that 60-80% of patients with advanced liver cancer experience pain of variable intensity, with about 30% suffering moderate to severe pain. Although the WHO three-step protocol has been considered the gold standard since 1986, its limitations have become increasingly evident, including inadequate response in approximately 10% of patients and significant side effects.

The methodology employed Bayesian network analysis using R software, evaluating three primary outcomes: pain relief efficacy, pain intensity measured by the Numeric Rating Scale (NRS), and adverse events. A random-effects model was applied within the Bayesian framework, with low heterogeneity detected (I² = 4%) and no significant inconsistency (P > 0.05). The results revealed important differences among the modalities. For pain relief efficacy, the SUCRA ranking showed that acupuncture combined with moxibustion had the best performance (SUCRA = 0.96), followed by acupuncture combined with herbal application (SUCRA = 0.65) and floating needling with herbal application (SUCRA = 0.64).

For pain intensity reduction (NRS), acupoint herbal application was superior (SUCRA = 0.72), followed by floating needling with herbal application (SUCRA = 0.70) and simple acupuncture (SUCRA = 0.63). Regarding adverse events, herbal application demonstrated the best safety profile (SUCRA = 0.80), followed by simple acupuncture (SUCRA = 0.74) and heat-sensitive moxibustion (SUCRA = 0.72). The clinical implications are promising, suggesting that integrating specific acupuncture modalities into the standard protocol may not only improve pain control but also reduce reliance on opioids and their associated side effects. Proposed mechanisms include the regulation of neurotransmitters such as endorphins, serotonin, and norepinephrine, as well as improvement of local microcirculation through the thermal effect of moxibustion.

Herbal application offers additional advantages through transdermal absorption of active compounds and simultaneous stimulation of acupoints. However, the study has significant limitations that should be considered when interpreting the results. The CINeMA assessment classified the quality of evidence as low, primarily due to within-study bias and incoherence. Most of the included studies presented poorly rigorous methodology, with vague or absent descriptions of randomization and allocation concealment methods.

The nature of acupuncture interventions makes blinding particularly challenging, increasing the risk of performance and detection bias. Additionally, there is substantial clinical heterogeneity among the studies in terms of acupoint selection, stimulation parameters, treatment duration, and frequency. The sparse network structure limits some direct comparisons, forcing reliance on indirect comparisons that may introduce additional uncertainty. The studies focused primarily on short-term outcomes, lacking systematic evaluation of long-term effects on quality of life, functional status, and analgesic dosage.

For clinical application, the results suggest that acupuncture may serve as a valuable adjuvant therapy in cancer pain management, particularly in patients who do not respond adequately to opioids or who experience significant side effects. The selection of the specific modality should consider individual patient characteristics, type of pain, and therapeutic goals. Future research should prioritize high-quality multicenter clinical trials with adequately calculated samples, standardized but flexible intervention protocols allowing for individualization, and long-term follow-up including objective biomarkers and quality-of-life measures.