Men with high-grade prostatic intraepithelial neoplasia (PIN) remain at high risk for prostate cancer even with a subsequent negative biopsy: Results of a prospective study

Abstract

1024 Background: High-grade prostatic intraepithelial neoplasia (PIN) has been identified largely based on observational data and small studies as a risk factor for prostate cancer. The incidence of cancer was prospectively assessed in 130 men with high-grade PIN treated with placebo for 1 year in a Phase IIB cancer-prevention study (n=514 including treated arms). Methods: Of 130 patients randomized to placebo, 109 had at least one on-study biopsy. The majority (85%) was white. At baseline, the mean age of placebo-treated men was 64.9 years; mean prostate-specific antigen (PSA) was 4.9 mg/mL; and mean total testosterone was 409 ng/dL. All men had been assessed as having high-grade PIN and no evidence of cancer on a biopsy conducted within 6 months before study entry (8.9 cores on average). Patients were rebiopsied at 6 and 12 months (minimum 8 cores per biopsy) to assess for the presence of high-grade PIN and prostate cancer. Initial and subsequent biopsies were evaluated by a central pathologist (Bostwick Laboratories) for diagnosis of high-grade PIN and prostate cancer. Results: At the 6-month biopsy, 15.7% of men with no evidence of cancer on prestudy biopsy were diagnosed with prostate cancer. A large number of these patients are assumed to have had undiagnosed prostate cancer upon entry into the trial. At the 12-month biopsy, 17.4% of men cancer-free on both prestudy and 6-month biopsies were diagnosed with prostate cancer. The cumulative risk of prostate cancer diagnosis in these placebo-treated men with no evidence of cancer on the prestudy biopsy was 31.2%. Conclusions: This prospective study confirms that men with high-grade PIN are at significant risk of prostate cancer. More than 30% of men with high-grade PIN were diagnosed with prostate cancer on subsequent biopsies over a 1-year period. Nearly 20% of patients were diagnosed with prostate cancer at 12 months despite a negative 6-month biopsy, which may not have been repeated at 12 months had they not been on study. These findings highlight the need to closely monitor patients with high-grade PIN through serial biopsies and to develop interventions to prevent cancer in men at high risk. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GTx