Most radiotherapy recommendations in recent National Comprehensive Cancer Network (NCCN) guidelines are based on expert opinion rather than high-level evidence, according to a study published in Advances in Radiation Oncology

The study showed that less than 10% of radiotherapy recommendations in 2020 NCCN guidelines were supported by category 1 consensus and levels of evidence (CE).

“The NCCN clinical guidelines influence medical practice, payor coverage, and standards of care,” the researchers wrote. “To our knowledge, no prior study has sought to describe the CE concerning radiation therapy recommendations in the NCCN guidelines.”

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The researchers evaluated the distribution of CE underlying treatment recommendations for the 20 most common cancers in the United States that have at least 10 radiotherapy recommendations in 2020 NCCN guidelines. 

In total, the researchers reviewed 761 radiotherapy recommendations. The category distributions were as follows:

  • 9.7% of recommendations were category 1 (based on high-level evidence, with uniform NCCN consensus that the intervention is appropriate)
  • 80.5% were category 2A (based on lower-level evidence, with uniform NCCN consensus)
  • 8.4% were category 2B (based on lower-level evidence, with NCCN consensus)
  • 1.3% were category 3 (based on any level of evidence, with major NCCN disagreement). 

The researchers also analyzed the recommendations by disease site and found that cervical and breast cancers had the highest proportion of category 1 CE — 33% and 31%, respectively. In contrast, hepatobiliary, bone, pancreatic, and uterine cancers, as well as melanoma, had no category 1 CE. 

Systemic therapy recommendations had a higher proportion of category 1 CE than did radiotherapy recommendations. For systemic therapy, 12.3% of recommendations were category 1, 66.5% were category 2A, 19.0% were category 2B, and 1.9% were category 3. 

“This analysis … highlights the need for more investment in high-quality randomized trials in radiation oncology to address clinical benefit and also the added benefit of alternative technologies (ie, proton therapy vs photons),” the researchers wrote. “Well-conducted randomized controlled trials are the only method to reliably test new treatment interventions, and this painstaking process should not be replaced by other strategies, like population-based observational studies.”

Disclosures: One study author declared an affiliation with Varian Medical Systems, Inc. Please see the original reference for a full list of disclosures.


Noy M, Rich BJ, Llorente R, et al. Levels of evidence for radiation therapy recommendations in the National Comprehensive Cancer Network (NCCN) clinical guidelines. Adv Radiat Oncol. Published online October 29, 2021. doi:10.1016/j.adro.2021.100832