Melissa Assel1, Anders Dahlin2, David Ulmert3, Anders Bergh4, Pär Stattin5, Hans Lilja6, Andrew J Vickers7. 1. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 2. Department of Clinical Microbiology, Lund University, Skåne University Hospital, Malmö, Sweden. 3. Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden; Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 4. Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden. 5. Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden; Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University Hospital, Umeå, Sweden. 6. Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Departments of Laboratory Medicine and Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Translational Medicine, Lund University, Malmö, Sweden; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK. Electronic address: liljah@mskcc.org. 7. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: vickersa@mskcc.org.
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.
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.
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