Date of Award

January 2019

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Preston Sprenkle

Abstract

Accurate identification of clinically significant prostate cancers (PCa) and avoiding over-biopsy remains challenging. We sought to establish characteristics of patients with metastatic disease, when to consider prostate biopsy after multiparametric-MRI (mp-MRI), and the optimal number and location of cores needed for mp-MRI ultrasound fusion biopsy to detect clinically significant prostate cancer.

Using the National Cancer Database, I stratified patients by age ≤ 55 years and examined sociodemographic factors associated with the diagnosis of metastatic PCa. In a prospective IRB-approved study, patients at high suspicion for PCa underwent multiparametric-MRI (mp-MRI) followed by transrectal ultrasound guided systematic prostate biopsy from December 2012 to September 2017. Of these, 100 had no suspicious regions of interest (ROI) prospectively identified on mp-MRI. In patients with ROI on mp-MRI, biopsy cores were taken from each ROI with an even distribution followed by 12-core systematic biopsy. In subset of patients, ROI were targeted using a predetermined template.

Among younger men with PCa, factors limiting access to care (low income, uninsured status, and living far from the treatment center) were significantly associated with the diagnosis of metastatic versus localized disease. For men with a negative mp-MRI, overall cancer detection was 27% (27/100). The negative predictive value of a negative mp-MRI was 73% for all prostate cancer and 97% for Gleason ≥ 7 prostate cancer. In patients with positive mp-MRI, 77% (279/361) of G≥3+4 tumors, and 72% (137/189) of G>3+4 tumors were detected on two-core sampling of a lesion. Clinically significant cancer detection using a two-core approach was 84% (147/176) in biopsy-naïve patients, 73% (69/94) in prior negative, and 68% (60/88) of men on active surveillance. Detection of G≥3+4 and G>3+4 cancers did not differ significantly by biopsy location nor when conducted in a predetermined sequence.

Young-age metastatic disease is associated with socioeconomic factors that limit access to healthcare. Patients with a negative mp-MRI can likely avoid systematic biopsy. Sampling two cores of mp-MRI-evident lesions at the time of fusion biopsy misses nearly one-quarter of clinically significant PCa that would be detected on additional sampling.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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