Login to Access Video or Poster Abstract: MP38-08
Sources of Funding: This work was supported by David H. Koch provided through the Prostate Cancer Foundation; the Sidney Kimmel Center for Prostate and Urologic Cancers; SPORE grant from the National Cancer Institute to Dr. H. Scher (grant number P50-CA92629); and a National Institutes of Health/National Cancer Institute Cancer Center Support Grant to MSKCC (grant number P30-CA008748). This work also received funding support in part from the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre Program in UK, the Swedish Cancer Society (project nr 14-0722), the Swedish Research Council (VR-MH project nr 2016-02974), and the Prostate Cancer Foundation Young Investigator Award 2012.

Introduction

Lead-time is of key importance in cancer early detection, but cannot be directly measured. We previously provided estimates of lead-time for prostate cancer using archived blood samples from cohorts followed for many years without screening. We determined the association between lead-time and grade at diagnosis to provide insight into whether grade progresses or is stable over time.

Methods

Participants were selected from three population-based Swedish cohorts followed without screening: 871 men aged 37 - 70 with PSA 3 - 10 ng / mL at blood draw and subsequently diagnosed with prostate cancer of whom 326 were diagnosed with high-grade disease (Gleason grade ≥7; Gleason grade group (GGG) ≥2). Multivariable logistic regression was used to predict high versus low-grade prostate cancer at diagnosis in terms of lead-time: time between elevated PSA and clinical diagnosis. Multivariable linear regression was used to test the association between lead time and PSA.

Results

After adjustment for cohort and age, the odds of high-grade disease increased 1.11 (95% C.I. 1.08, 1.14) per year increase in lead time (p<0.0001), with no evidence of differences by age group or cohort. Higher PSA predicted a shorter lead time of 0.44 (95% C.I. 0.25, 0.63; p<0.0001) years per 1 ng / mL higher PSA after adjustment for cohort and age. There was no interaction between PSA and grade, suggesting that the longer lead time of high-grade tumors is not simply related to age. PSA was significantly associated with grade after adjusting for lead time, cohort, and age (OR=1.09; 95% CI 1.00, 1.19; p=0.048) suggesting that both grade and PSA increase over time. A limitation is our assumption that men with an elevated PSA subsequently diagnosed with cancer would have biopsy-detectable cancer at the time of PSA elevation.

Conclusions

Our data support grade-progression, that were we to follow a prostate over time we would see a transition from benign to GGG 1, then to GGG 2 or higher disease. We cannot know whether this effect is because a GGG 1 becomes GGG 2, or a new focus of GGG 2 arises in a prostate already containing a GGG 1 tumor.

Funding

This work was supported by David H. Koch provided through the Prostate Cancer Foundation; the Sidney Kimmel Center for Prostate and Urologic Cancers; SPORE grant from the National Cancer Institute to Dr. H. Scher (grant number P50-CA92629); and a National Institutes of Health/National Cancer Institute Cancer Center Support Grant to MSKCC (grant number P30-CA008748). This work also received funding support in part from the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre Program in UK, the Swedish Cancer Society (project nr 14-0722), the Swedish Research Council (VR-MH project nr 2016-02974), and the Prostate Cancer Foundation Young Investigator Award 2012.