Episode one of two on the Colorectal Cancer, Polyps, and Diverticular Disease chapter, tracing the neoplastic pathway from average-risk screening through molecular subtyping to stage-based treatment and polyp surveillance. The organizing thread is mechanism: why screening starts at forty-five, why MLH1 loss reflexes to BRAF, and why histology sets the surveillance interval. Topics covered Average-risk CRC screening at 45 Screening modalities and intervals Adenoma-carcinoma vs serrated pathways Universal mismatch-repair reflex testing TNM staging and workup Stage-based and molecular treatment Rectal cancer and total mesorectal excision Post-polypectomy surveillance intervals Key decisions Average-risk screening starts at 45, runs to 75, shared decision 76 to 85; FDR with CRC or advanced adenoma starts at 40 or 10 years before youngest case with 5-year intervals. A positive stool DNA with a high-quality negative colonoscopy needs no further GI workup; any positive noninvasive test is an indication for diagnostic colonoscopy. MLH1 loss reflexes to BRAF or MLH1 methylation testing; MLH1 loss with positive BRAF is sporadic serrated disease with no germline implication, while MSH2, MSH6, or isolated PMS2 loss goes straight to germline testing. At least 12 lymph nodes must be examined for adequate node staging; there is no lower fallback minimum. MSI-high stage II tumors do not benefit from single-agent fluorouracil and are usually observed; stage III gets mandatory oxaliplatin-based adjuvant chemotherapy. Anti-EGFR therapy is used only in RAS-wild-type left-sided primaries; MSI-high metastatic disease gets first-line pembrolizumab; BRAF-mutant disease gets a BRAF inhibitor plus cetuximab. Advanced adenoma is 10 mm or larger, villous or tubulovillous histology, or high-grade dysplasia, any one sufficient, and gets a 3-year surveillance interval; any proximal hyperplastic polyp 10 mm or larger is managed as a sessile serrated lesion. For the full chapter with MCQs, tables, and primary-guideline references, visit www.boardpearls.com. Questions or feedback: [email protected]. (00:00) - Introduction (01:06) - Screening ages and risk tiers (02:01) - Screening modalities and intervals (04:30) - Molecular pathways and subtypes (05:48) - Reflex MMR and Lynch testing (08:34) - Staging and treatment by stage (09:57) - Stage four molecular therapy (12:57) - Polyps and surveillance intervals

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“What did the council decide on item 42?” — answered with the speaker and the moment.

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