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

Mikropoulos C1, Selkirk CGH2,3, Saya S1, Bancroft E1,4, Vertosick E5, Dadaev T1, Brendler C2, Page E1, Dias A1,4, Evans DG6, Rothwell J6, Maehle L7, Axcrona K8, Richardson K9,10, Eccles D11,12, Jensen T13, Osther PJ13, van Asperen CJ14, Vasen H15, Kiemeney LA16, Ringelberg J15, Cybulski C17, Wokolorczyk D17, Hart R18, Glover W18, Lam J19, Taylor L19, Salinas M20, Feliubadaló L20, Oldenburg R21, Cremers R16, Verhaegh G16, van Zelst-Stams WA15, Oosterwijk JC22, Cook J23, Rosario DJ24, Buys SS25, Conner T25, Domchek S26, Powers J26, Ausems MG27, Teixeira MR28,29, Maia S28, Izatt L30, Schmutzler R31, Rhiem K31, Foulkes WD32, Boshari T32, Davidson R33, Ruijs M34, Helderman-van den Enden AT35, Andrews L36, Walker L37, Snape K38, Henderson A39, Jobson I39, Lindeman GJ40,41,42, Liljegren A43, Harris M44, Adank MA45, Kirk J46,47, Taylor A48, Susman R49, Chen-Shtoyerman R50, Pachter N51,52, Spigelman A53,54,55, Side L56, Zgajnar J57, Mora J58, Brewer C59,60, Gadea N61, Brady AF62, Gallagher D63, van Os T64, Donaldson A65, Stefansdottir V66, Barwell J67,68, James PA9,10,69, Murphy D10, Friedman E70,71, Nicolai N72, Greenhalgh L73, Obeid E74, Murthy V75, Copakova L76, McGrath J60, Teo SH77, Strom S78, Kast K79,80,81, Leongamornlert DA1, Chamberlain A1, Pope J1, Newlin AC3, Aaronson N34, Ardern-Jones A4, Bangma C21, Castro E82, Dearnaley D1,4, Eyfjord J83, Falconer A84, Foster CS85, Gronberg H86, Hamdy FC37,87, Johannsson O66, Khoo V4, Lubinski J17, Grindedal EM7, McKinley J9, Shackleton K40, Mitra AV88, Moynihan C1, Rennert G89, Suri M90, Tricker K6; IMPACT study collaborators, Moss S91, Kote-Jarai Z1, Vickers A5, Lilja H87,92, Helfand BT2, Eeles RA1,4.

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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.British Journal of Cancer advance online publication, 4 January 2018; doi:10.1038/bjc.2017.429 www.bjcancer.com.