Postoperative Desmoid Risk in FAP by APC Variant and Family History

Key Takeaways

• Among patients with FAP after prophylactic colonic surgery, postoperative desmoid incidence was 63% with APC variants 3′ of codon 1399 and 12.7% with variants at or 5′; within both groups, incidence was higher with an affected first-degree relative.
• An affected first-degree relative was associated with higher incidence within both APC strata, and the combination with a distal variant marked the highest observed incidence.
• Desmoid incidence did not differ significantly between the reported surgical procedure categories within either APC stratum.

Desmoid disease can complicate risk-reducing colorectal surgery for people with familial adenomatous polyposis (FAP). Adenomatous polyposis coli (APC) variant location and an affected first-degree relative may both be known before surgery, but how they jointly relate to absolute postoperative risk is uncertain.

In a BJS Open postoperative desmoid risk study, investigators retrospectively reviewed a prospectively maintained polyposis registry at St Mark's Hospital in London, UK, including patients operated on elsewhere. The 1,261 eligible patients had constitutional APC pathogenic variants either 3′ of codon 1399 or at or 5′ of that codon. Positive family history meant a first-degree relative with genetically confirmed FAP and a clinical and/or radiological desmoid diagnosis; patients' desmoid diagnoses were likewise clinical and/or radiological. Eligibility required prophylactic colonic surgery and at least 5 years of postoperative follow-up. Patients without surgery, with desmoid diagnosed before or at surgery, or without operative details were excluded. Investigators compared proportions using Pearson's chi-squared or Fisher's exact test.

Postoperative desmoid incidence was 63% in the distal-variant group, compared with 12.7% in the at-or-5′ group. The distal-variant group comprised 48 patients, 35 of whom (73%) had an affected first-degree relative. Desmoids developed in 28 of those 35 (80%), versus 2 of 13 (15%) without a recorded affected relative; the family-history difference was statistically significant. In the at-or-5′ group, 180 of 1,213 patients (14.8%) had an affected first-degree relative. The distal-group estimate without a recorded affected relative rests on only 13 patients.

In the at-or-5′ group, postoperative desmoid incidence was 30% with an affected first-degree relative versus 9.7% without one, a statistically significant difference. Neither total colectomy versus proctocolectomy in the distal group nor proctocolectomy versus total or partial colectomy in the at-or-5′ group showed a statistically significant difference in desmoid incidence.

Retrospective ascertainment, a comparatively small distal-variant subgroup, and possible referral bias from outside operations at this London tertiary center constrain interpretation of absolute incidence. Routine systematic desmoid surveillance was not performed, so asymptomatic disease may have been missed. These associations do not establish effects caused by genotype, family history, or procedure, or show that changing surgery, its timing, or surveillance prevents desmoids.

The authors concluded that an affected first-degree relative was an important discriminator of postoperative desmoid risk in both APC groups. The high overall incidence with distal variants was largely confined to patients with that family history. Without a recorded affected relative, incidence was 15% with a distal variant and 9.7% with a variant at or 5′ of codon 1399; this contrast was not formally tested, and the distal estimate rests on 13 patients. These observational differences do not establish causation.

Clinician Questions

How was an unknown desmoid family history handled in the FAP postoperative risk comparison?

In the St Mark's Hospital analysis of patients with familial adenomatous polyposis (FAP), unknown desmoid family history was classified as no positive family history. The group without a recorded affected first-degree relative therefore could include patients whose history was unknown, not definitively negative.

Did the FAP desmoid risk analysis assess surgical approach or medication and hormonal exposures?

For patients with familial adenomatous polyposis (FAP) undergoing prophylactic colonic surgery, investigators compared broad operation categories but were not specifically powered to evaluate granular operative variables, including surgical approach. They also could not account for medication exposure or hormonal factors.

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