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

Christos Mikropoulos, Christina G Hutten Selkirk, Sibel Saya, Elizabeth Bancroft, Emily Vertosick, Tokhir Dadaev, Charles Brendler, Elizabeth Page, Alexander Dias, D Gareth Evans, Jeanette Rothwell, Lovise Maehle, Karol Axcrona, Kate Richardson, Diana Eccles, Thomas Jensen, Palle J Osther, Christi J van Asperen, Hans Vasen, Lambertus A Kiemeney, Janneke Ringelberg, Cezary Cybulski, Dominika Wokolorczyk, Rachel Hart, Wayne Glover, Jimmy Lam, Louise Taylor, Monica Salinas, Lidia Feliubadaló, Rogier Oldenburg, Ruben Cremers, Gerald Verhaegh, Wendy A van Zelst-Stams, Jan C Oosterwijk, Jackie Cook, Derek J Rosario, Saundra S Buys, Tom Conner, Susan Domchek, Jacquelyn Powers, Margreet Gem Ausems, Manuel R Teixeira, Sofia Maia, Louise Izatt, Rita Schmutzler, Kerstin Rhiem, William D Foulkes, Talia Boshari, Rosemarie Davidson, Marielle Ruijs, Apollonia Tjm Helderman-van den Enden, Lesley Andrews, Lisa Walker, Katie Snape, Alex Henderson, Irene Jobson, Geoffrey J Lindeman, Annelie Liljegren, Marion Harris, Muriel A Adank, Judy Kirk, Amy Taylor, Rachel Susman, Rakefet Chen-Shtoyerman, Nicholas Pachter, Allan Spigelman, Lucy Side, Janez Zgajnar, Josefina Mora, Carole Brewer, Neus Gadea, Angela F Brady, David Gallagher, Theo van Os, Alan Donaldson, Vigdis Stefansdottir, Julian Barwell, Paul A James, Declan Murphy, Eitan Friedman, Nicola Nicolai, Lynn Greenhalgh, Elias Obeid, Vedang Murthy, Lucia Copakova, John McGrath, Soo-Hwang Teo, Sara Strom, Karin Kast, Daniel A Leongamornlert, Anthony Chamberlain, Jenny Pope, Anna C Newlin, Neil Aaronson, Audrey Ardern-Jones, Chris Bangma, Elena Castro, David Dearnaley, Jorunn Eyfjord, Alison Falconer, Christopher S Foster, Henrik Gronberg, Freddie C Hamdy, Oskar Johannsson, Vincent Khoo, Jan Lubinski, Eli Marie Grindedal, Joanne McKinley, Kylie Shackleton, Anita V Mitra, Clare Moynihan, Gad Rennert, Mohnish Suri, Karen Tricker, IMPACT study collaborators, Sue Moss, Zsofia Kote-Jarai, Andrew Vickers, Hans Lilja, Brian T Helfand, Rosalind A Eeles, Christos Mikropoulos, Christina G Hutten Selkirk, Sibel Saya, Elizabeth Bancroft, Emily Vertosick, Tokhir Dadaev, Charles Brendler, Elizabeth Page, Alexander Dias, D Gareth Evans, Jeanette Rothwell, Lovise Maehle, Karol Axcrona, Kate Richardson, Diana Eccles, Thomas Jensen, Palle J Osther, Christi J van Asperen, Hans Vasen, Lambertus A Kiemeney, Janneke Ringelberg, Cezary Cybulski, Dominika Wokolorczyk, Rachel Hart, Wayne Glover, Jimmy Lam, Louise Taylor, Monica Salinas, Lidia Feliubadaló, Rogier Oldenburg, Ruben Cremers, Gerald Verhaegh, Wendy A van Zelst-Stams, Jan C Oosterwijk, Jackie Cook, Derek J Rosario, Saundra S Buys, Tom Conner, Susan Domchek, Jacquelyn Powers, Margreet Gem Ausems, Manuel R Teixeira, Sofia Maia, Louise Izatt, Rita Schmutzler, Kerstin Rhiem, William D Foulkes, Talia Boshari, Rosemarie Davidson, Marielle Ruijs, Apollonia Tjm Helderman-van den Enden, Lesley Andrews, Lisa Walker, Katie Snape, Alex Henderson, Irene Jobson, Geoffrey J Lindeman, Annelie Liljegren, Marion Harris, Muriel A Adank, Judy Kirk, Amy Taylor, Rachel Susman, Rakefet Chen-Shtoyerman, Nicholas Pachter, Allan Spigelman, Lucy Side, Janez Zgajnar, Josefina Mora, Carole Brewer, Neus Gadea, Angela F Brady, David Gallagher, Theo van Os, Alan Donaldson, Vigdis Stefansdottir, Julian Barwell, Paul A James, Declan Murphy, Eitan Friedman, Nicola Nicolai, Lynn Greenhalgh, Elias Obeid, Vedang Murthy, Lucia Copakova, John McGrath, Soo-Hwang Teo, Sara Strom, Karin Kast, Daniel A Leongamornlert, Anthony Chamberlain, Jenny Pope, Anna C Newlin, Neil Aaronson, Audrey Ardern-Jones, Chris Bangma, Elena Castro, David Dearnaley, Jorunn Eyfjord, Alison Falconer, Christopher S Foster, Henrik Gronberg, Freddie C Hamdy, Oskar Johannsson, Vincent Khoo, Jan Lubinski, Eli Marie Grindedal, Joanne McKinley, Kylie Shackleton, Anita V Mitra, Clare Moynihan, Gad Rennert, Mohnish Suri, Karen Tricker, IMPACT study collaborators, Sue Moss, Zsofia Kote-Jarai, Andrew Vickers, Hans Lilja, Brian T Helfand, Rosalind A Eeles

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.

Conflict of interest statement

Hans Lilja holds patents for free PSA, hK2, and intact PSA assays, and is named, along with Andrew J. Vickers, on a patent application for a statistical method to detect prostate cancer. The marker assay patents and the patent application for the statistical model has been licensed and commercialised as the 4Kscore by OPKO Diagnostics. Drs Vickers and Lilja receive royalties from sales of this test. Additionally, Dr Lilja owns stock and Dr Vickers owns stock options in OPKO. Professor Rosalind Eeles—Janssen: provided medical education support to GU ASCO Feb 2013. Succinct Communications: received an honorarium and expenses for attending and speaking at UK Cancer Convention Oct 2013. The authors have no other conflict of interest to declare.

Figures

Figure 1
Figure 1
Consort diagram of study population. The two bolded cohorts were included for in-depth analysis, as they had 3 or more PSA values available for analysis and underwent a prostate biopsy.

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