Association between lead time and prostate cancer grade: Evidence of grade progression from long-term follow-up of large population-based cohorts not subject to prostate-specific antigen screening Journal Article


Authors: Assel, M.; Dahlin, A.; Ulmert, D.; Bergh, A.; Stattin, P.; Lilja, H.; Vickers, A. J.
Article Title: Association between lead time and prostate cancer grade: Evidence of grade progression from long-term follow-up of large population-based cohorts not subject to prostate-specific antigen screening
Abstract: Background: Lead time (LT) is of key importance in early detection of cancer, but cannot be directly measured. We have previously provided LT estimates for prostate cancer (PCa) using archived blood samples from cohorts followed for many years without screening. Objective: To determine the association between LT and PCa grade at diagnosis to provide an insight into whether grade progresses or is stable over time. Design, setting, and participants: The setting was three long-term epidemiologic studies in Sweden including men not subject to prostate-specific antigen (PSA) screening. The cohort included 1041 men with PSA of 3–10 ng/ml at blood draw and subsequently diagnosed with PCa with grade data available. Outcome measurements and statistical analysis: Multivariable logistic regression was used to predict high-grade (Gleason grade group ≥2 or World Health Organization grade 3) versus low-grade PCa at diagnosis in terms of LT, defined as the time between the date of elevated PSA and the date of PCa diagnosis with adjustment for cohort and age. Results and limitations: The probability that PCa would be high grade at diagnosis increased with LT. Among all men combined, the risk of high-grade disease increased with LT (odds ratio 1.13, 95% confidence interval [CI] 1.10–1.16; p < 0.0001), with no evidence of differences in effect by age group or cohort. Higher PSA predicted shorter LT by 0.46 yr (95% CI 0.28–0.64; p < 0.0001) per 1 ng/ml increase in PSA. However, there was no interaction between PSA and grade, suggesting that the longer LT for high-grade tumors is not simply related to age. Limitations include the assumption that men with elevated PSA and subsequently diagnosed with PCa would have had biopsy-detectable PCa at the time of PSA elevation. Conclusions: Our data support grade progression, whereby following a prostate over time would reveal transitions from benign to low-grade and then high-grade PCa. Patient summary: Men with a longer lead time between elevated prostate-specific antigen and subsequent prostate cancer diagnosis were more likely to have high-grade cancers at diagnosis. The probability that a cancer will be of high grade at diagnosis increases with the lead time. Our findings provide evidence of grade progression, whereby a prostate followed over time would exhibit transitions from benign to low-grade to high-grade prostate cancer. © 2017 European Association of Urology
Keywords: adult; aged; major clinical study; cancer growth; follow up; cancer grading; prostate specific antigen; cohort analysis; high risk patient; age; prostate cancer; gleason score; screening; psa; human; male; priority journal; article; lead-time
Journal Title: European Urology
Volume: 73
Issue: 6
ISSN: 0302-2838
Publisher: Elsevier Science, Inc.  
Date Published: 2018-06-01
Start Page: 961
End Page: 967
Language: English
DOI: 10.1016/j.eururo.2017.10.004
PROVIDER: scopus
PMCID: PMC5911245
PUBMED: 29066048
DOI/URL:
Notes: Article -- Export Date: 1 June 2018 -- Source: Scopus
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MSK Authors
  1. Hans Gosta Lilja
    286 Lilja
  2. Andrew J Vickers
    560 Vickers
  3. Hans David Staffan Ulmert
    49 Ulmert
  4. Melissa Jean Assel
    39 Assel