William J. Gradishar, MD, Director of the Maggie Daley Center for Women’s Cancer Care at Robert H. Lurie Comprehensive Cancer Center, opened day 3 of this year’s Miami Breast Cancer Conference with an enlightening discussion on the impact of clinical guidelines—and their necessary evolution over time.

The NCCN’s impact

Nodding to the more than 20 years he spent on the National Comprehensive Cancer Network (NCCN) guidelines committee, Dr. Gradishar explained that the NCCN guidelines are the most thorough and most commonly used clinical practice guidelines available in all areas of medicine. In fact, 88 NCCN guidelines feature 228 algorithms that apply to 97% of cancer cases.

There are over 63 guidelines panels comprising nearly 2,000 panel members—all of whom completed about 49,000 hours of volunteer work in 2024 alone—and include everyone from oncologists, pathologists, and radiologists, to even patient-advocates. “We want their voice,” Dr. Gradishar said.

Guidelines aren’t perfect—and they’re not meant to be

Dr. Gradishar then underscored a few key details: “We also need to acknowledge guidelines aren’t perfect. We know that. They do not capture every clinical scenario. And they are not static, but rather dynamic and subject to change as data rapidly emerges, challenging the status quo.” 

Guidelines are dynamic. They’re not meant to remain the same over time, but change, to reflect what's going on in our specialty.

He referenced the four categories of clinical evidence: Category 1 is based on high-level evidence, whereas 2A is based on lower-level evidence that 85% of the panel supports. He said that nothing “below a 2A” will be considered in current guidelines. From there, the NCCN assigns interventions into three categories: Preferred Intervention, Other Recommended Intervention, and Useful in Certain Circumstances. “We try to assign a level of evidence, but when you get into small phase trials and case reports and anecdotes… the enthusiasm for highlighting these diminishes,” Dr. Gradishar said.

In the context of the clinic

When working with patients, physicians must strike a delicate balance—guidelines exist for a reason, of course, but some patients fall outside of the box. “You don’t want to rigidly shove [every patient] into a guideline,” Dr. Gradishar said, noting that some patients may need care that falls below a level 1 evidence level. “You have to use your clinical judgement. Perfect is the enemy of good.”

In breast cancer, specifically, data from SEER-Medicare showed that guidelines improved both cost and patient outcomes.

Williams CP, Azuero A, Kenzik KM, et al. Guideline Discordance and Patient Cost Responsibility in Medicare Beneficiaries With Metastatic Breast Cancer. J Natl Compr Canc Netw. 2019 Oct 1;17(10):1221-1228. doi: 10.6004/jnccn.2019.7316. 

“Denials go down when you follow guidelines because insurance companies look to guidelines,” Dr. Gradishar said. “You can reduce disparities by applying guidelines broadly.”