Acupuncture as Treatment of Cancer-Therapy Induced Fatigue: A Critical Systematic Review with a Focus on the Methodological Assessment of Blinding

This critical systematic review examined the efficacy of acupuncture in the treatment of cancer-therapy-related fatigue, with a special focus on the methodologic assessment of blinding. The German researchers conducted a comprehensive search across five databases in April 2024, identifying 1,599 initial studies, of which 15 randomized controlled trials enrolling 1,346 patients were included in the final analysis.

The study population included patients with various types of cancer, with 1,207 women and 137 men, aged 18-80 years. Interventions varied significantly, including traditional acupuncture (11 studies), electroacupuncture (2 studies), and other modalities such as ATAS acupuncture and mind-regulating acupuncture. Control arms included sham acupuncture, usual care, or wait list.

Results were heterogeneous and contradictory. While some studies comparing real versus sham acupuncture reported significant effects on cancer-related fatigue, others did not find advantages. Studies comparing acupuncture with usual care frequently reported positive effects. However, the reliability of these findings is severely limited by critical methodologic issues.

Risk-of-bias assessment using the RoB-2 tool revealed that 14 of the 15 studies were classified as "high risk of bias" due to issues such as insufficient blinding, incomplete data analysis, and randomization issues. Only one study (Cheng et al., 2017) was considered low risk of bias and showed a significant reduction in fatigue with acupuncture compared with sham acupuncture (p < 0.001) in patients with lung cancer.

One of the main challenges identified was the difficulty of achieving adequate blinding in acupuncture studies. The "deqi" sensation — a mixture of numbness, tingling, or dull pain considered an indicator of effective needle placement — complicates the blinding process because it is difficult to reproduce or is completely overlooked in placebo-controlled studies. This sensation was actively sought in six studies in the real acupuncture arm while being avoided in the sham arms, creating potential bias.

GRADE assessment also showed very low certainty of evidence, consistent with RoB-2 results. Significant clinical and methodologic heterogeneity, together with high risk of bias and low GRADE scores, were strong arguments against performing a meta-analysis, since combining data from such heterogeneous and low-certainty studies would not lead to meaningful conclusions.

Reported adverse events were minimal, including mild pain, dizziness, localized bleeding, and bruising. Many studies did not report adverse events or did not provide information on side effects.

Methodologic limitations included small sample sizes, high dropout rates, inadequate analysis (many studies used per-protocol rather than intention-to-treat analysis), and lack of effective blinding. In addition, patient-acupuncturist interaction may have influenced results through attention and expectation effects.

The authors conclude that the heterogeneous results and methodologic limitations of existing studies prevent definitive conclusions about the efficacy of acupuncture in the treatment of cancer-related fatigue. The analysis highlights the need to use more rigorous designs and more comprehensive assessment tools in future studies to better understand the role of acupuncture in managing post-treatment fatigue in oncology.