**Background:** Familial adenomatous polyposis (FAP) is an autosomal dominant disorder caused by germline mutations in the APC gene, leading to hundreds to thousands of colorectal adenomas from early adolescence. Without prophylactic surgery, colorectal cancer (CRC) develops almost inevitably by age 50. FAP accounts for 0.5–1% of all CRC cases, with a prevalence of 2.29–3.2 per 100,000. Extracolonic manifestations include duodenal cancer (cumulative risk 4.5% at age 57, rising to 18% at 75), desmoid tumors (20%), congenital hypertrophy of the retinal pigment epithelium (60%), and others. Attenuated FAP (aFAP) presents with fewer than 100 adenomas and later onset. This review aims to present updated perspectives on diagnosis, surveillance, surgical management, and chemoprevention.
**Methods:** This is a narrative review synthesizing current literature on FAP diagnosis, surveillance, surgical options, and chemopreventive agents. The authors discuss genetic testing guidelines (e.g., NCCN), endoscopic techniques (conventional, fluorescence, chromoendoscopy), surveillance protocols for colorectal and extracolonic manifestations, and surgical procedures (total colectomy with ileorectal anastomosis [IRA], proctocolectomy with ileal pouch-anal anastomosis [IPAA], and proctocolectomy with end ileostomy). Chemoprevention trials reviewed include those on aspirin, celecoxib, rofecoxib, sulindac, combination therapies (sulindac/erlotinib, sulindac/DFMO, celecoxib/DFMO), fish oil, turmeric, ascorbic acid, rapamycin, mesalazine, and metformin.
**Key Results:** Genetic testing detects APC mutations in 85% of FAP patients. Fluorescence endoscopy showed higher diagnostic accuracy for depth of cancerous invasion compared to chromoendoscopy (89% vs 68%). Surveillance guidelines recommend colonoscopy/sigmoidoscopy every 1–3 years starting at age 10–14, and upper GI endoscopy at age 20–25. Surgical options: IRA has a 6.1–11.2% risk of rectal cancer; IPAA has a 1.1–1.9% risk of cancer (mostly in the rectal cuff). Prophylactic surgery is recommended before age 27 for classic FAP and before 31 for aFAP. Chemoprevention: The CAPP1 trial (n=227) found no benefit of aspirin 600 mg on polyp burden, only a reduction in size of the largest polyp (p=0.02). Celecoxib 400 mg twice daily for 6 months significantly reduced polyp number in a tattooed area (p<0.05). Rofecoxib was withdrawn due to increased thrombotic events. Sulindac showed initial polyp reduction but later studies failed to show statistical significance. Combination sulindac/erlotinib reduced duodenal polyp burden in the FAPEST trial but had adverse events. Sulindac/DFMO combination showed an 80% risk reduction for disease progression in a post-hoc analysis. Fish oil (EPA) significantly reduced polyp number and burden in a target area over 6 months. Curcumin/quercetin reduced polyp size and number in a pilot study (n=5), but a larger trial (n=44) found no significant difference. Ascorbic acid showed no benefit in two trials. Rapamycin reduced polyp size and dysplasia in a pediatric study (n=2) but had adverse events in a pilot study (n=4). Metformin had no effect on polyp number or size but reduced mTOR signaling (p-S6 expression). Mesalazine reduced polyp diameter in 4 FAP patients with ulcerative colitis and, in the J-FAPP IV trial, reduced recurrence of polyps >5 mm when combined with aspirin.
**Clinical Implications:** Early diagnosis through genetic testing and endoscopic surveillance is critical to prevent CRC. Surgical choice must be individualized based on polyp burden, genotype, and patient factors. Chemoprevention remains experimental; no agent has proven sufficiently effective and safe for routine use. Ongoing trials targeting novel pathways (e.g., mTOR, MAP kinase, bile acid signaling) may offer future options. The review underscores the need for larger, well-designed studies to establish evidence-based chemopreventive strategies.