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; Sue Moss; Zsofia Kote-Jarai; Andrew Vickers; Hans Lilja; Brian T. Helfand; Rosalind A. Eeles

doi:10.1038/bjc.2017.429

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. KiemeneyJanneke 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, Sue Moss, Zsofia Kote-Jarai, Andrew Vickers, Hans Lilja, Brian T. Helfand, Rosalind A. Eeles

Research output: Contribution to journal › Article › peer-review

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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 3/43 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.

Original language	English
Pages (from-to)	266-276
Number of pages	11
Journal	British Journal of Cancer
Volume	118
Issue number	2
DOIs	https://doi.org/10.1038/bjc.2017.429
State	Published - 1 Jan 2018
Externally published	Yes

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10.1038/bjc.2017.429

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Mikropoulos, C., Selkirk, C. G. H., Saya, S., Bancroft, E., Vertosick, E., Dadaev, T., Brendler, C., Page, E., Dias, A., Evans, D. G., Rothwell, J., Maehle, L., Axcrona, K., Richardson, K., Eccles, D., Jensen, T., Osther, P. J., Van Asperen, C. J., Vasen, H., ... Eeles, R. A. (2018). Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition. British Journal of Cancer, 118(2), 266-276. https://doi.org/10.1038/bjc.2017.429

@article{592d8edcae874bf5a7182ce9a172dd6b,

title = "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 3/43 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.",

author = "Christos Mikropoulos and Selkirk, {Christina G.Hutten} and Sibel Saya and Elizabeth Bancroft and Emily Vertosick and Tokhir Dadaev and Charles Brendler and Elizabeth Page and Alexander Dias and Evans, {D. Gareth} and Jeanette Rothwell and Lovise Maehle and Karol Axcrona and Kate Richardson and Diana Eccles and Thomas Jensen and Osther, {Palle J.} and {Van Asperen}, {Christi J.} and Hans Vasen and Kiemeney, {Lambertus A.} and Janneke Ringelberg and Cezary Cybulski and Dominika Wokolorczyk and Rachel Hart and Wayne Glover and Jimmy Lam and Louise Taylor and Monica Salinas and Lidia Feliubadal{\'o} and Rogier Oldenburg and Ruben Cremers and Gerald Verhaegh and {Van Zelst-Stams}, {Wendy A.} and Oosterwijk, {Jan C.} and Jackie Cook and Rosario, {Derek J.} and Buys, {Saundra S.} and Tom Conner and Susan Domchek and Jacquelyn Powers and Ausems, {Margreet Gem} and Teixeira, {Manuel R.} and Sofia Maia and Louise Izatt and Rita Schmutzler and Kerstin Rhiem and Foulkes, {William D.} and Talia Boshari and Rosemarie Davidson and Marielle Ruijs and {Helderman-Van Den Enden}, {Apollonia Tjm} and Lesley Andrews and Lisa Walker and Katie Snape and Alex Henderson and Irene Jobson and Lindeman, {Geoffrey J.} and Annelie Liljegren and Marion Harris and Adank, {Muriel A.} and Judy Kirk and Amy Taylor and Rachel Susman and Rakefet Chen-Shtoyerman and Nicholas Pachter and Allan Spigelman and Lucy Side and Janez Zgajnar and Josefina Mora and Carole Brewer and Neus Gadea and Brady, {Angela F.} and David Gallagher and {Van Os}, Theo and Alan Donaldson and Vigdis Stefansdottir and Julian Barwell and James, {Paul A.} and Declan Murphy and Eitan Friedman and Nicola Nicolai and Lynn Greenhalgh and Elias Obeid and Vedang Murthy and Lucia Copakova and John McGrath and Teo, {Soo Hwang} and Sara Strom and Karin Kast and Leongamornlert, {Daniel A.} and Anthony Chamberlain and Jenny Pope and Newlin, {Anna C.} and Neil Aaronson and Audrey Ardern-Jones and Chris Bangma and Elena Castro and David Dearnaley and Jorunn Eyfjord and Alison Falconer and Foster, {Christopher S.} and Henrik Gronberg and Hamdy, {Freddie C.} and Oskar Johannsson and Vincent Khoo and Jan Lubinski and Grindedal, {Eli Marie} and Joanne McKinley and Kylie Shackleton and Mitra, {Anita V.} and Clare Moynihan and Gad Rennert and Mohnish Suri and Karen Tricker and Sue Moss and Zsofia Kote-Jarai and Andrew Vickers and Hans Lilja and Helfand, {Brian T.} and Eeles, {Rosalind A.}",

note = "Funding Information: We are indebted to all of the men who are taking part in this study. This research is coordinated by the Institute of Cancer Research, London, UK and is supported by grants from Cancer Research UK (Grant references (C5047/A21332, C5047/A13232 and C5047/ A17528) and The Ronald and Rita McAulay Foundation. Mr and Mrs Jack Baker for the study in NorthShore University HealthSystem, Evanston, Illinois and Myriad Genetics Laboratory, Salt Lake City, Utah, for providing research BRCA testing rates for NorthShore University HealthSystem participants. We acknowledge funding from the NIHR to the Biomedical Research Center at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, at Central Manchester Foundation Trust and the Oxford Biomedical Research Centre Program. We acknowledge that in Australia, this project was co-funded by Cancer Council Tasmania and Cancer Australia, grant number 1006349 (2011–2013), Prostate Cancer Foundation of Australia, grant number PCFA PRO4 (2008) and Cancer Councils of Victoria and South Australia, grant number 400048 (2006–2008), The Victorian Cancer Agency Clinical Trial Capacity CTCB08_14, Cancer Australia & Prostate Cancer Foundation of Australia (2014–2016) grant number 1059423, and Translational grants EOI09_50. The Association of International Cancer Research funded data collection in The Netherlands (AICR 10–0596). We acknowledge funding from the Basser Center for BRCA (to S Domchek). We acknowledge funding from the National Cancer Institute [P30-CA008748], the Sidney Kimmel Center for Prostate and Urologic Cancers, and David H. Koch through the Prostate Cancer Foundation, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre Program in UK, Swedish Cancer Society (Cancerfonden project no. 11–0624), and the Swedish Research Council (VR-MH project no. 2016– 02974). We acknowledge funding from the Slovenian Research Agency, Research programme P3–0352. Elena Castro acknol-wedges funding from a Juan de la Cierva{\textquoteright} fellowship from MINIECO (grant reference IJCI-2014–19129). We acknowledge the support of the Asociaci{\'o}n Espa{\~n}ola Contra el C{\'a}ncer (AECC), the Instituto de Salud Carlos III (organismo adscrito al Ministerio de Econom{\'i}a y Competitividad) and {\textquoteleft}Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa{\textquoteright} (PI10/01422, PI13/00285, PIE13/00022, PI16/00563 and CIBERONC) and the Institut Catal{\`a} de la Salut and Autonomous Government of Catalonia (2009SGR290, 2014SGR338 and PERIS Project MedPerCan). We acknowledge David Fisas, Consol Lopez and Dr Nuria Calvo for their involvement in the project at Hospital de Sant Pau, Barcelona. We are grateful to the members of the Data and Safety Monitoring Committee: S. Duffy (Chair), P. White (UK NEQAS representative) and J. McGrath (BAUS representative). We acknowledge the contribution of past members of the IMPACT Steering Committee: J. Melia, S. Moss, P. Wilson and G. Mitchell.",

year = "2018",

month = jan,

day = "1",

doi = "10.1038/bjc.2017.429",

language = "אנגלית",

volume = "118",

pages = "266--276",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

number = "2",

}

Mikropoulos, C, Selkirk, CGH, Saya, S, Bancroft, E, Vertosick, E, Dadaev, T, Brendler, C, Page, E, Dias, A, Evans, DG, Rothwell, J, Maehle, L, Axcrona, K, Richardson, K, Eccles, D, Jensen, T, Osther, PJ, Van Asperen, CJ, Vasen, H, Kiemeney, LA, Ringelberg, J, Cybulski, C, Wokolorczyk, D, Hart, R, Glover, W, Lam, J, Taylor, L, Salinas, M, Feliubadaló, L, Oldenburg, R, Cremers, R, Verhaegh, G, Van Zelst-Stams, WA, Oosterwijk, JC, Cook, J, Rosario, DJ, Buys, SS, Conner, T, Domchek, S, Powers, J, Ausems, MG, Teixeira, MR, Maia, S, Izatt, L, Schmutzler, R, Rhiem, K, Foulkes, WD, Boshari, T, Davidson, R, Ruijs, M, Helderman-Van Den Enden, AT, Andrews, L, Walker, L, Snape, K, Henderson, A, Jobson, I, Lindeman, GJ, Liljegren, A, Harris, M, Adank, MA, Kirk, J, Taylor, A, Susman, R, Chen-Shtoyerman, R, Pachter, N, Spigelman, A, Side, L, Zgajnar, J, Mora, J, Brewer, C, Gadea, N, Brady, AF, Gallagher, D, Van Os, T, Donaldson, A, Stefansdottir, V, Barwell, J, James, PA, Murphy, D, Friedman, E, Nicolai, N, Greenhalgh, L, Obeid, E, Murthy, V, Copakova, L, McGrath, J, Teo, SH, Strom, S, Kast, K, Leongamornlert, DA, Chamberlain, A, Pope, J, Newlin, AC, Aaronson, N, Ardern-Jones, A, Bangma, C, Castro, E, Dearnaley, D, Eyfjord, J, Falconer, A, Foster, CS, Gronberg, H, Hamdy, FC, Johannsson, O, Khoo, V, Lubinski, J, Grindedal, EM, McKinley, J, Shackleton, K, Mitra, AV, Moynihan, C, Rennert, G, Suri, M, Tricker, K, Moss, S, Kote-Jarai, Z, Vickers, A, Lilja, H, Helfand, BT & Eeles, RA 2018, 'Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition', British Journal of Cancer, vol. 118, no. 2, pp. 266-276. https://doi.org/10.1038/bjc.2017.429

TY - JOUR

T1 - Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition

AU - Mikropoulos, Christos

AU - Selkirk, Christina G.Hutten

AU - Saya, Sibel

AU - Bancroft, Elizabeth

AU - Vertosick, Emily

AU - Dadaev, Tokhir

AU - Brendler, Charles

AU - Page, Elizabeth

AU - Dias, Alexander

AU - Evans, D. Gareth

AU - Rothwell, Jeanette

AU - Maehle, Lovise

AU - Axcrona, Karol

AU - Richardson, Kate

AU - Eccles, Diana

AU - Jensen, Thomas

AU - Osther, Palle J.

AU - Van Asperen, Christi J.

AU - Vasen, Hans

AU - Kiemeney, Lambertus A.

AU - Ringelberg, Janneke

AU - Cybulski, Cezary

AU - Wokolorczyk, Dominika

AU - Hart, Rachel

AU - Glover, Wayne

AU - Lam, Jimmy

AU - Taylor, Louise

AU - Salinas, Monica

AU - Feliubadaló, Lidia

AU - Oldenburg, Rogier

AU - Cremers, Ruben

AU - Verhaegh, Gerald

AU - Van Zelst-Stams, Wendy A.

AU - Oosterwijk, Jan C.

AU - Cook, Jackie

AU - Rosario, Derek J.

AU - Buys, Saundra S.

AU - Conner, Tom

AU - Domchek, Susan

AU - Powers, Jacquelyn

AU - Ausems, Margreet Gem

AU - Teixeira, Manuel R.

AU - Maia, Sofia

AU - Izatt, Louise

AU - Schmutzler, Rita

AU - Rhiem, Kerstin

AU - Foulkes, William D.

AU - Boshari, Talia

AU - Davidson, Rosemarie

AU - Ruijs, Marielle

AU - Helderman-Van Den Enden, Apollonia Tjm

AU - Andrews, Lesley

AU - Walker, Lisa

AU - Snape, Katie

AU - Henderson, Alex

AU - Jobson, Irene

AU - Lindeman, Geoffrey J.

AU - Liljegren, Annelie

AU - Harris, Marion

AU - Adank, Muriel A.

AU - Kirk, Judy

AU - Taylor, Amy

AU - Susman, Rachel

AU - Chen-Shtoyerman, Rakefet

AU - Pachter, Nicholas

AU - Spigelman, Allan

AU - Side, Lucy

AU - Zgajnar, Janez

AU - Mora, Josefina

AU - Brewer, Carole

AU - Gadea, Neus

AU - Brady, Angela F.

AU - Gallagher, David

AU - Van Os, Theo

AU - Donaldson, Alan

AU - Stefansdottir, Vigdis

AU - Barwell, Julian

AU - James, Paul A.

AU - Murphy, Declan

AU - Friedman, Eitan

AU - Nicolai, Nicola

AU - Greenhalgh, Lynn

AU - Obeid, Elias

AU - Murthy, Vedang

AU - Copakova, Lucia

AU - McGrath, John

AU - Teo, Soo Hwang

AU - Strom, Sara

AU - Kast, Karin

AU - Leongamornlert, Daniel A.

AU - Chamberlain, Anthony

AU - Pope, Jenny

AU - Newlin, Anna C.

AU - Aaronson, Neil

AU - Ardern-Jones, Audrey

AU - Bangma, Chris

AU - Castro, Elena

AU - Dearnaley, David

AU - Eyfjord, Jorunn

AU - Falconer, Alison

AU - Foster, Christopher S.

AU - Gronberg, Henrik

AU - Hamdy, Freddie C.

AU - Johannsson, Oskar

AU - Khoo, Vincent

AU - Lubinski, Jan

AU - Grindedal, Eli Marie

AU - McKinley, Joanne

AU - Shackleton, Kylie

AU - Mitra, Anita V.

AU - Moynihan, Clare

AU - Rennert, Gad

AU - Suri, Mohnish

AU - Tricker, Karen

AU - Moss, Sue

AU - Kote-Jarai, Zsofia

AU - Vickers, Andrew

AU - Lilja, Hans

AU - Helfand, Brian T.

AU - Eeles, Rosalind A.

N1 - Funding Information: We are indebted to all of the men who are taking part in this study. This research is coordinated by the Institute of Cancer Research, London, UK and is supported by grants from Cancer Research UK (Grant references (C5047/A21332, C5047/A13232 and C5047/ A17528) and The Ronald and Rita McAulay Foundation. Mr and Mrs Jack Baker for the study in NorthShore University HealthSystem, Evanston, Illinois and Myriad Genetics Laboratory, Salt Lake City, Utah, for providing research BRCA testing rates for NorthShore University HealthSystem participants. We acknowledge funding from the NIHR to the Biomedical Research Center at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, at Central Manchester Foundation Trust and the Oxford Biomedical Research Centre Program. We acknowledge that in Australia, this project was co-funded by Cancer Council Tasmania and Cancer Australia, grant number 1006349 (2011–2013), Prostate Cancer Foundation of Australia, grant number PCFA PRO4 (2008) and Cancer Councils of Victoria and South Australia, grant number 400048 (2006–2008), The Victorian Cancer Agency Clinical Trial Capacity CTCB08_14, Cancer Australia & Prostate Cancer Foundation of Australia (2014–2016) grant number 1059423, and Translational grants EOI09_50. The Association of International Cancer Research funded data collection in The Netherlands (AICR 10–0596). We acknowledge funding from the Basser Center for BRCA (to S Domchek). We acknowledge funding from the National Cancer Institute [P30-CA008748], the Sidney Kimmel Center for Prostate and Urologic Cancers, and David H. Koch through the Prostate Cancer Foundation, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre Program in UK, Swedish Cancer Society (Cancerfonden project no. 11–0624), and the Swedish Research Council (VR-MH project no. 2016– 02974). We acknowledge funding from the Slovenian Research Agency, Research programme P3–0352. Elena Castro acknol-wedges funding from a Juan de la Cierva’ fellowship from MINIECO (grant reference IJCI-2014–19129). We acknowledge the support of the Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III (organismo adscrito al Ministerio de Economía y Competitividad) and ‘Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa’ (PI10/01422, PI13/00285, PIE13/00022, PI16/00563 and CIBERONC) and the Institut Català de la Salut and Autonomous Government of Catalonia (2009SGR290, 2014SGR338 and PERIS Project MedPerCan). We acknowledge David Fisas, Consol Lopez and Dr Nuria Calvo for their involvement in the project at Hospital de Sant Pau, Barcelona. We are grateful to the members of the Data and Safety Monitoring Committee: S. Duffy (Chair), P. White (UK NEQAS representative) and J. McGrath (BAUS representative). We acknowledge the contribution of past members of the IMPACT Steering Committee: J. Melia, S. Moss, P. Wilson and G. Mitchell.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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 3/43 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.

AB - 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 3/43 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.

UR - http://www.scopus.com/inward/record.url?scp=85041064923&partnerID=8YFLogxK

U2 - 10.1038/bjc.2017.429

DO - 10.1038/bjc.2017.429

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 29301143

AN - SCOPUS:85041064923

SN - 0007-0920

VL - 118

SP - 266

EP - 276

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 2

ER -

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

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