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 Feliubadalo; 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 G. E. M. Ausems; Manuel R. Teixeira; Sofia Maia; Louise Izatt; Rita Schmutzler; Kerstin Rhiem; William D. Foulkes; Talia Boshari; Rosemarie Davidson; Marielle Ruijs; Apollonia van den Enden; IMPACT Study Collaborators; 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 Feliubadalo, 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 G. E. M. Ausems, Manuel R. Teixeira, Sofia Maia, Louise Izatt, Rita Schmutzler, Kerstin Rhiem, William D. Foulkes, Talia Boshari, Rosemarie Davidson, Marielle Ruijs, Apollonia van den Enden, IMPACT Study Collaborators, Rosalind A. Eeles^*

^*Corresponding author for this work

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

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(-1), 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
Publication status	Published - 23 Jan 2018

Keywords

prostate cancer
genetic predisposition
predictive model
PSA velocity
BRCA1
BRCA2
BRCA2 MUTATION CARRIERS
PSA VELOCITY
RISK
CURABILITY
INCREASE
WINDOW
IMPACT
DEATH

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Cite this

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{e645d3e877d3403ebc1fa291c673e2ab,

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 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml(-1), 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.",

keywords = "prostate cancer, genetic predisposition, predictive model, PSA velocity, BRCA1, BRCA2, BRCA2 MUTATION CARRIERS, PSA VELOCITY, RISK, CURABILITY, INCREASE, WINDOW, IMPACT, DEATH",

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 Feliubadalo 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 G. E. M.} 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 {van den Enden}, Apollonia and {IMPACT Study Collaborators} and Eeles, {Rosalind A.}",

year = "2018",

month = jan,

day = "23",

doi = "10.1038/bjc.2017.429",

language = "English",

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, Feliubadalo, 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, MGEM, Teixeira, MR, Maia, S, Izatt, L, Schmutzler, R, Rhiem, K, Foulkes, WD, Boshari, T, Davidson, R, Ruijs, M, van den Enden, A, IMPACT Study Collaborators & 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 - Feliubadalo, 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 G. E. M.

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 - van den Enden, Apollonia

AU - IMPACT Study Collaborators

AU - Eeles, Rosalind A.

PY - 2018/1/23

Y1 - 2018/1/23

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 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml(-1), 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 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml(-1), 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.

KW - prostate cancer

KW - genetic predisposition

KW - predictive model

KW - PSA velocity

KW - BRCA1

KW - BRCA2

KW - BRCA2 MUTATION CARRIERS

KW - PSA VELOCITY

KW - RISK

KW - CURABILITY

KW - INCREASE

KW - WINDOW

KW - IMPACT

KW - DEATH

U2 - 10.1038/bjc.2017.429

DO - 10.1038/bjc.2017.429

M3 - Article

SN - 0007-0920

VL - 118

SP - 266

EP - 276

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 2

ER -