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

IMPACT study collaborators

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)266-276
Number of pages11
JournalBritish Journal of Cancer
Volume118
Issue number2
DOIs
Publication statusPublished - Jan 2018

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Genetic Predisposition to Disease
Prostate-Specific Antigen
Early Detection of Cancer
Prostatic Neoplasms
Biopsy
Prostate
Reading

Keywords

  • Adult
  • Aged
  • BRCA1 Protein/genetics
  • BRCA2 Protein/genetics
  • Early Detection of Cancer/methods
  • Genetic Predisposition to Disease
  • Germ-Line Mutation
  • Humans
  • Kallikreins/metabolism
  • Logistic Models
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Prostate-Specific Antigen/metabolism
  • Prostatic Neoplasms/diagnosis

Cite this

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

In: British Journal of Cancer, Vol. 118, No. 2, 01.2018, p. 266-276.

Research output: Contribution to journalArticle

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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-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.",
keywords = "Adult, Aged, BRCA1 Protein/genetics, BRCA2 Protein/genetics, Early Detection of Cancer/methods, Genetic Predisposition to Disease, Germ-Line Mutation, Humans, Kallikreins/metabolism, Logistic Models, Male, Middle Aged, Neoplasm Grading, Prostate-Specific Antigen/metabolism, Prostatic Neoplasms/diagnosis",
author = "{IMPACT study collaborators} and 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 Nicola Nicolai",
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T1 - Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition

AU - IMPACT study collaborators

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 - Nicolai, Nicola

PY - 2018/1

Y1 - 2018/1

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 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 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.

KW - Adult

KW - Aged

KW - BRCA1 Protein/genetics

KW - BRCA2 Protein/genetics

KW - Early Detection of Cancer/methods

KW - Genetic Predisposition to Disease

KW - Germ-Line Mutation

KW - Humans

KW - Kallikreins/metabolism

KW - Logistic Models

KW - Male

KW - Middle Aged

KW - Neoplasm Grading

KW - Prostate-Specific Antigen/metabolism

KW - Prostatic Neoplasms/diagnosis

U2 - 10.1038/bjc.2017.429

DO - 10.1038/bjc.2017.429

M3 - Article

C2 - 29301143

VL - 118

SP - 266

EP - 276

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 2

ER -