There are limited data on the effectiveness of cancer screening in biallelic MMR-gene pathogenic variant carriers. Published recommendations represent expert opinion and are mostly extrapolated from cancer screening studies in other groups at increased risk of specific cancers.rr
The International Replication Repair Deficiency Consortium (IRRDC) (formerly the BMMRD Consortium) recently reported tumour and survival data for a cohort of patients (N=110), some of whom had surveillance and the majority of whom were followed prospectively (81%).rr The 4-year overall survival was 79% in patients undergoing the full surveillance schedule, versus 15% for patients not undergoing surveillance. On the basis of this evidence surveillance for GI, solid and CNS tumours is now recommended for unaffected individuals with CMMRD.
Colorectal adenoma
Colorectal adenomas are common (estimated lifetime penetrance >90%) with more than 50% of reported CMMRD cases having adenoma detected before age 10 years.r Multiple colorectal adenomas have been diagnosed in a child aged 6 years.r There is in vitro evidence that CMMRD-related adenoma show faster progression from benign to malignant than equivalent lesions in heterozygotes (i.e. Lynch syndrome). Consider increasing colonoscopy to 6 monthly if adenoma are detected.
Colorectal cancer
One of the most commonly reported cancers is colorectal carcinoma (CRC), with approximately 50% of reported CRC diagnosed under age 16 years.rr Colonoscopy is of proven benefit in a number of inherited colorectal polyposis syndromes and it is reasonable to assume at least some benefit in CMMRD. In the presymptomatically screened cohort all GI tumours were detected prior to symptom onset.r There is no published data on the long term benefits of preventative colectomy in CMMRD.
Small bowel cancer
A recent report from the IRRDC detailed the outcome of video capsule endoscopy (VCE) for small bowel surveillance in 17 patients with CMMRD (total of 38 procedures).r Three patients had small bowel neoplasia detected by VCE (2 with adenoma with high grade dysplasia at 16 and 13 years, 1 with jejunal adenocarcinoma at 15 years). However 4 patients with negative VCE were subsequently diagnosed with duodenal neoplasia (false negatives).
Haematological malignancy
The IRRDC reported haematological malignancies in 19% of 105 patients undergoing surveillance with the protocol published in 2017. There is no evidence that routine full blood count in asymptomatic individuals leads to earlier detection of haematological malignancy, reduced mortality or improved survival and this is not recommended.rr
Urinary tract malignancy
The IRRDC reported urinary tract malignancies in 3-4% of 105 patients undergoing surveillance with the protocol published in 2017. They recommend annual urinalysis from age 10 years. There is no evidence that this leads to reduced mortality or improved survival.rr
Brain tumours
Brain tumours have similar penetrance to CRC, but with a younger median age at diagnosis (9 years). There are multiple reports of brain tumours in children under age 5 years.rrrr
General
- Clinicians should be aware of the increased risk for malignancies that are usually diagnosed in adulthood.
- Clinicians should be aware of the increased risk of a second malignancy after a first diagnosis.
- Education to patients and families should be tailored to the specific situation.