A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): Initial results from an international prospective study
The Lancet Oncology — Bancroft EK, Page EC, Brook MN, et al. | October 22, 2021
Men with MSH2 and MSH6 (mismatch repair genes) pathogenic variants showed a higher incidence of prostate cancer than age-matched non-carrier controls, post first prostate-specific antigen (PSA) screening round. Overall, targeted PSA screening should be performed in these men to find out those with clinically significant prostate cancer.
According to emerging data, pathogenic variants in mismatch repair genes raise the risk of early-onset aggressive prostate cancer.
In the IMPACT study, PSA screening was prospectively evaluated in men with germline mismatch repair pathogenic variants.
Men with germline mismatch repair pathogenic variants (MLH1, MSH2, MSH6) and 184 non-carrier controls were included.
For prostate cancer, the overall incidence was 1·9%.
Incidence of prostate cancer in MSH2 carriers was 4·3%, in MSH2 non-carrier controls was 0·5%, it was 3·0% in MSH6 carriers and none were identified among the MLH1 carriers, MLH1 non-carrier controls, and MSH6 non-carrier controls.
When a PSA threshold of higher than 3·0 ng/mL was applied, there was a higher incidence of prostate cancer in MSH2 carriers than in MSH2 non-carrier controls (4·3% vs 0·5%) and MSH6 carriers than MSH6 non-carrier controls (3·0% vs 0%).
Overall positive predictive value of 51·4% was reported for biopsy using a PSA threshold of 3·0 ng/mL, and this value was 32·1% (20·3–46·0) for a PSA threshold of 3·0 ng/mL.