Advanced

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

Assel, Melissa; Dahlin, Anders LU ; Ulmert, David LU ; Bergh, Anders; Stattin, Pär; Lilja, Hans LU and Vickers, Andrew J. (2018) In European Urology 73(6). p.961-967
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Lead-time, Prostate cancer, PSA, Screening
in
European Urology
volume
73
issue
6
pages
7 pages
publisher
Elsevier
external identifiers
  • scopus:85045959048
ISSN
0302-2838
DOI
10.1016/j.eururo.2017.10.004
language
English
LU publication?
yes
id
bea50a54-ff4f-4244-a070-ec9b48f514e4
date added to LUP
2018-05-04 07:25:30
date last changed
2019-02-20 11:16:05
@article{bea50a54-ff4f-4244-a070-ec9b48f514e4,
  abstract     = {<p>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 &lt; 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 &lt; 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.</p>},
  author       = {Assel, Melissa and Dahlin, Anders and Ulmert, David and Bergh, Anders and Stattin, Pär and Lilja, Hans and Vickers, Andrew J.},
  issn         = {0302-2838},
  keyword      = {Lead-time,Prostate cancer,PSA,Screening},
  language     = {eng},
  month        = {06},
  number       = {6},
  pages        = {961--967},
  publisher    = {Elsevier},
  series       = {European Urology},
  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},
  url          = {http://dx.doi.org/10.1016/j.eururo.2017.10.004},
  volume       = {73},
  year         = {2018},
}