Level of evidence underlying recommendations in the National Comprehensive Cancer Network (NCCN) Supportive Care guidelines.

606 Background: NCCN guidelines are among the most comprehensive and widely adopted clinical practice standards in oncology, frequently used by both clinicians and payors across the United States. Theys encompass three main categories: treatment, detection/prevention/risk reduction, and supportive care. While the evidence base for treatment recommendations has been examined in prior studies—and early detection guidelines largely align with those from other major medical societies—the strength of evidence supporting recommendations in supportive care guidelines remains poorly characterized. Methods: We conducted a systematic analysis of the categories of evidence and consensus (EC) supporting recommendations in 5 widely utilized NCCN supportive care guidelines (versions 2025): antiemesis, cancer-related fatigue, distress management, hematopoietic growth factors, and smoking cessation. Recommendations were classified into the following EC levels: category 1 (high-level evidence with uniform consensus [>85%]), category 2A (lower-level evidence with uniform consensus), category 2B (lower-level evidence with moderate consensus [50–84%]), and category 3 (any level of evidence with major disagreement). Results: Of the 120 recommendations found in the 5 guidelines of supportive care, the proportions of category I, IIA, IIB, and III EC were 18%, 82%, and 0%, and 0%, respectively. Recommendations with category I EC were found in antiemesis supportive care (30%), cancer-related fatigue (21%), distress management (12%), hematopoietic growth factors (20%), and smoking cessation (13%) guidelines. Conclusions: A substantial proportion of recommendations in the NCCN supportive care guidelines are derived from lower levels of evidence. While these guidelines are invaluable in standardizing care and guiding clinical decision-making, their reliance on expert opinion underscores a critical gap in the oncology evidence base. This situation presents both a challenge and a compelling opportunity to design and conduct rigorous clinical research that can validate current practices, inform future recommendations, and further improve patient outcomes. Level of recommendation by guideline. Guideline Recommendations I IIA IIB III Antiemesis 23 30% 70% 0% 0% Cancer-related fatigue 19 21% 79% 0% 0% Distress management 43 12% 88% 0% 0% Growth factors 19 20% 80% 0% 0% Smoking cessation 16 13% 87% 0% 0%