What is the best screening approach for cancer in patients with Familial Adenomatous Polyposis (FAP) and Peutz-Jegher's syndrome?

Screening Recommendations for FAP and Peutz-Jeghers Syndrome

For FAP mutation carriers, begin flexible sigmoidoscopy or colonoscopy annually starting at age 10-12 years and continue lifelong until colectomy is performed; for Peutz-Jeghers syndrome mutation carriers, begin colonoscopy at age 8 years and repeat every 3 years thereafter. 1, 2

Familial Adenomatous Polyposis (FAP) Screening Protocol

Initial Screening Timeline

• Start flexible sigmoidoscopy at age 10-12 years for at-risk family members or confirmed APC mutation carriers 2, 1, 3
• The early teens (age 13-15 years) is also acceptable as a starting point, though age 10-12 is increasingly preferred 2
• Annual screening intervals are mandatory once initiated 1, 3

Surveillance Intensity Based on Findings

• Once adenomas are detected, escalate to annual colonoscopy (not just sigmoidoscopy) until colectomy is planned 1, 3
• Continue annual surveillance lifelong if surgery is deferred for personal reasons, though this is strongly discouraged beyond age 25 2
• After colectomy with ileorectal anastomosis, the retained rectum requires annual surveillance for life due to 12-29% cancer risk 2, 4

Critical Age Considerations

• No cases of colorectal cancer occur before age 10 in classical FAP, with only incidental cases between ages 11-15 2
• Prophylactic colectomy is recommended between ages 16-25 years to prevent inevitable cancer development 2, 4
• Patients with codon 1309 mutations develop severe polyposis earlier and require more aggressive surveillance 1

Attenuated FAP Variant

• For attenuated FAP (AFAP), begin total colonoscopy every 2 years starting at age 18-20 years due to right-sided colonic adenoma predominance 2, 1
• This differs from classical FAP because polyps appear later and are fewer in number 1

Peutz-Jeghers Syndrome Screening Protocol

Colonoscopy Schedule

• Begin colonoscopy at age 8 years for confirmed mutation carriers or those with characteristic mucocutaneous pigmentation 2
• Repeat colonoscopy every 3 years thereafter 2, 4
• This interval is based on the slower growth rate of hamartomatous polyps compared to adenomatous polyps in FAP

Additional Surveillance Requirements

• Small bowel surveillance is equally critical, as polyps >1.5-2 cm risk intussusception and require elective resection 4
• Upper gastrointestinal endoscopy should be performed concurrently with colonoscopy 4
• Annual gynecological examination and pelvic ultrasound starting at age 30-35 years for females due to elevated gynecologic cancer risk 4

Key Distinctions Between the Two Syndromes

Polyp Characteristics

• FAP produces hundreds to thousands of adenomatous polyps with 100% malignant transformation risk if untreated 5, 6
• Peutz-Jeghers produces hamartomatous polyps with lower but still significantly elevated cancer risk 4

Screening Rationale Differences

• FAP screening starts earlier (age 10-12) because adenomas appear in early teens and progress rapidly to cancer 2, 1
• Peutz-Jeghers screening starts at age 8 but uses 3-year intervals because hamartomatous polyps grow more slowly 2, 4

Genetic Testing Priority

• Genetic testing should be performed in both syndromes to identify mutation carriers and spare non-carriers from unnecessary surveillance 2
• For FAP, APC gene testing includes DNA sequencing and large rearrangement analysis 2, 1
• Negative genetic testing in FAP family members allows transition to average-risk screening protocols 2

Common Pitfalls to Avoid

• Do not delay FAP screening beyond age 15, as polyps typically appear by mean age 13.4 years and 60% have >50 polyps at diagnosis 6
• Do not use sigmoidoscopy alone for attenuated FAP, as right-sided adenomas will be missed 2, 1
• Do not assume negative family history excludes FAP, as 30-40% of cases represent de novo mutations 1, 7
• Do not stop surveillance after colectomy in FAP, as the retained rectum or pouch requires lifelong annual examination 2, 4