Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition
Mikropoulos, Christos; Selkirk, Christina G.Hutten; Selkirk, Christina G.Hutten; Saya, Sibel; Bancroft, Elizabeth; Bancroft, Elizabeth; Vertosick, Emily; Dadaev, Tokhir; Brendler, Charles; Page, Elizabeth; Dias, Alexander; Dias, Alexander; Evans, D. Gareth; Rothwell, Jeanette; Maehle, Lovise; Axcrona, Karol; Richardson, Kate; Richardson, Kate; Eccles, Diana; Eccles, Diana; Jensen, Thomas; Osther, Palle J.; Van Asperen, Christi J.; Vasen, Hans; Kiemeney, Lambertus A.; Ringelberg, Janneke; Cybulski, Cezary; Wokolorczyk, Dominika; Hart, Rachel; Glover, Wayne; Lam, Jimmy; Taylor, Louise; Salinas, Monica; Feliubadaló, Lidia; Oldenburg, Rogier; Cremers, Ruben; Verhaegh, Gerald; Van Zelst-Stams, Wendy A.; Oosterwijk, Jan C.; Cook, Jackie; Rosario, Derek J.; Buys, Saundra S.; Conner, Tom; Domchek, Susan; Powers, Jacquelyn; Ausems, Margreet Gem; Teixeira, Manuel R.; Teixeira, Manuel R.; Maia, Sofia; Izatt, Louise; Schmutzler, Rita; Rhiem, Kerstin; Foulkes, William D.; Boshari, Talia; Davidson, Rosemarie; Ruijs, Marielle; Helderman-Van Den Enden, Apollonia Tjm; Andrews, Lesley; Walker, Lisa; Snape, Katie; Henderson, Alex; Jobson, Irene; Lindeman, Geoffrey J.; Lindeman, Geoffrey J.; Lindeman, Geoffrey J.; Liljegren, Annelie; Harris, Marion; Adank, Muriel A.; Kirk, Judy; Kirk, Judy; Taylor, Amy; Susman, Rachel; Chen-Shtoyerman, Rakefet; Pachter, Nicholas; Pachter, Nicholas; Spigelman, Allan; Spigelman, Allan; Spigelman, Allan; Side, Lucy; Zgajnar, Janez; Mora, Josefina; Brewer, Carole; Brewer, Carole; Gadea, Neus; Brady, Angela F.; Gallagher, David; Van Os, Theo; Donaldson, Alan; Stefansdottir, Vigdis; Barwell, Julian; Barwell, Julian; James, Paul A.; James, Paul A.; James, Paul A.; Murphy, Declan; Friedman, Eitan; Friedman, Eitan; Nicolai, Nicola; Greenhalgh, Lynn; Obeid, Elias
(2018) British Journal of Cancer, volume 118, issue 2, pp. 266 - 276
(Article)
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
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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.
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Keywords: Oncology, Cancer Research
ISSN: 0007-0920
Publisher: Nature Publishing Group
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’ 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.
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