Select updates outlined below. Check out the full guidelines by creating a FREE account at https://www.nccn.org/guidelines/category_2
Colorectal, Endometrial, & Gastric Cancer
V1.2025 – Released June 13th, 2025
- MSH2 & EPCAM (LS-C 1 of 5 – Page 50): Added row for sarcoma risk, primarily for MSH2, but indicated there is no clear evidence to support surveillance at this time.
- PMS2 (LS-E 1 of 5 – Page 60): Removed cancer risks for ovarian, renal pelvis and ureter, bladder, gastric, small bowel, pancreas, biliary tract, prostate, breast (female), brain, and skin to reflect that association with these cancers is unclear.
- Replaced with: While other LS-associated cancers have been observed in individuals with PMS2 LS, it is unclear whether PMS2 LS carriers have increased risk for these cancers (thus, should be individualized based on personal and family cancer history and clinical judgment)
- CDH1 (HGAST-A – Page 97):
- Stomach cancer – now limited to diffuse in table (signet ring removed)
- HGAST-B 4 of 5: Footnote c added: if there are mucosal abnormalities, recommend a referral to an expert center for discussion of surgery.
- TP53 (GENE-15 – Page 117):
- Risks: Colon cancer absolute risk: 5-20% (changed from >20%)
- Management: Colonoscopy and upper endoscopy every 2-5 years starting at age 20-25 (changed from age 25) or 5 years before earliest colorectal cancer in the family.
Breast, Ovarian, Pancreatic, & Prostate Cancer
V1.2026 – Released July 10th, 2025
- Testing: Ovarian Cancer Susceptibility (CRIT-4): expanded to include testing of non-epithelial ovarian tumors – sex-cord tumors with annular tubules (SCTAT) and small cell carcinoma of the ovary (hypercalcemic type) (SCCOHT) at any age. Consider testing for those with serous tubal intraepithelial carcinoma (STIC).
- CHEK2: Revised comment to reflect that risks in the table are for frameshift and missense pathogenic/likely pathogenic (P/LP) variants (other than missense IIe157Thr, Ser428Phe, and Thr476Met). Specifically, indicated that there is emerging evidence that not all missense P/LP variants are low penetrance.
- PALB2 & TP53: Added prostate cancer risks and screening (starting at age 40).
- BRCA Management: BRCA-A (1 of 5): Sub-bullet added: Screening with clinical breast exam should continue after risk-reducing mastectomy. Routing screening with mammogram and breast MRI are not indicated.