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 OncologyBancroft EK, Page EC, Brook MN, et al. | October 22, 2021

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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.

Read the full article on The Lancet Oncology

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