Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition

Abstract

Background:Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort.Methods:PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV.Results:1634 participants had ⩾3 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml−l, PSAV was not significantly associated with presence of cancer or high-grade disease. PSAV did not add to PSA for predicting time to an elevated PSA. When comparing BRCA1/2 carriers to non-carriers, we found a significant interaction between BRCA status and last PSA before biopsy (P=0.031) and BRCA2 status and PSAV (P=0.024). However, PSAV was not predictive of biopsy outcome in BRCA2 carriers.Conclusions:PSA is more strongly predictive of PrCa in BRCA carriers than non-carriers. We did not find evidence that PSAV aids decision-making for BRCA carriers over absolute PSA value alone.

Screening for prostate cancer: protocol for updating multiple systematic reviews to inform a Canadian Task Force on Preventive Health Care guideline update

“…Using other biomarkers to determine an individual's risk of developing prostate cancer has been a relatively new approach and has not yet been applied in general population screening; however, many RNA, DNA, and proteinbased biomarkers in the urine, blood, and tissue samples have been studied to help predict the risk of prostate cancer [47][48][49][50][51][52][53][54][55][56][57]. Other tools or approaches for screening (coupled with PSA) for identifying adults at elevated risk include multiparametric magnetic resonance imaging (mpMRI), PSA velocity (PSAV), or risk calculators such as the Stockholm-3 model (S3M or STHLM3) [58][59][60][61]. PSA density, the PSA value (in ng/ml) divided by prostate volume (in CC), is another strategy used to predict prostate cancer, but has not been consistent in daily clinical practice over the years [62].…”

Hereditary Prostate Cancer: Genes Related, Target Therapy and Prevention

“…The IMPACT study evaluated PSA screening in men with a known genetic PCa predisposition due to BRCA1/2 mutations and found that a value of PSA >3 ng/mL is more strongly predictive in BRCA carriers than noncarriers [ 16 , 88 ].…”

“…In a multicenter study concerning early diagnosis for men carrying BRCA2 mutations, systematic PSA screening was recommended (Figure 3) [87]. The IMPACT study evaluated PSA screening in men with a kno predisposition due to BRCA1/2 mutations and found that a value of P more strongly predictive in BRCA carriers than noncarriers [16,88].…”

“…Other authors reported that BRCA mutations and MMR deficiency associated with a higher Gleason score [67,76,89]. However, their clinica cluding their utility in screening programs, is as yet undefined and, i have been found sensitive and specific enough to replace the PSA measu The IMPACT study evaluated PSA screening in men with a known genetic PCa predisposition due to BRCA1/2 mutations and found that a value of PSA >3 ng/mL is more strongly predictive in BRCA carriers than noncarriers [16,88].…”

Screening naar prostaatkanker bij mannen met een BRCA2 mutatie: adviezen voor de praktijk gebaseerd op resultaten van internationale studie

“…Hoewel het hier ging om een trend en er nog geen significant verschil kon worden aangetoond met de controlegroep, was de verwachting dat dit met grotere aantallen en een langere follow-upperiode wel significant zou kunnen worden [6]. Daarnaast is ook aangetoond dat PSA-screening meer prostaatcarcinomen vindt bij BRCA1 en BRCA2 dragers dan bij nietdragers [8].…”