The effectiveness of cancer screening in individuals with POLE and POLD1 pathogenic variants is still unclear. Recommendations have been extrapolated from cancer screening studies in other related hereditary cancer syndromes such as Lynch syndrome, MUTYH associated polyposis (MAP) and attenuated familial adenomatous polyposis (AFAP).
Data suggests polyposis may be more severe in POLE pathogenic variant carriers.rr For individuals with significant polyps (3 polyps before age 30 years or greater than 10 polyps in a lifetime), recommendations are based on MAP and includes colectomy when polyp burden becomes unmanageable.r
There is limited data regarding the appropriate surveillance frequency for individuals with POLE and POLD1 pathogenic variants. The recommendation for 2-yearly surveillance is thought to represent the best balance between risks and benefits of colonoscopy in individuals who have not yet had polyps identified.r
There have been no studies providing beneficial evidence for the use of aspirin in POLE and POLD1 pathogenic variant carriers. However, considerable evidence supports the effectiveness of aspirin as risk-reducing medication for colorectal cancer (CRC) in high-risk patients with Lynch syndrome (greater than 50% reduction in CRC risk).r Revised guidelines from the Cancer Council Australia have also made a strong recommendation to consider universal aspirin chemoprevention except where contraindicated, especially for those with excess cardiovascular risk.r Therefore, these recommendations have been included for individuals with POLE and POLD1 pathogenic variants.
Duodenal adenomas and/or cancer
There are no studies to show the efficacy of gastrointestinal endoscopy in reducing the risk for duodenal cancer. Surveillance recommendations have been based on the risk management guidelines for MUTYH-associated polyposis (MAP) and attenuated familial adenomatous polyposis (AFAP).r
Consider polypectomy in polymerase proofreading-associated polyposis (PPAP) when adenomas are 1cm or greater in size.r
Endometrial cancer risk is increased in POLE and POLD1 pathogenic variant carriers. Surveillance starting at age 40 years has been suggested although there is no evidence to support screening for endometrial cancer in other high risk groups such as individuals with Lynch syndrome.r There is limited evidence that there is an increased risk of ovarian cancer in POLD1 pathogenic variant carriers. The risk of endometrial and ovarian cancer warrants a discussion regarding risk-reducing hysterectomy and bilateral salpingo-oophorectomy.