(ChemotherapyAdvisor) – Oral toremifene did not lower the prostate cancer detection rate among men with isolated high-grade prostatic intraepithelial neoplasia (HGPIN) on biopsy; however, this group has a high likelihood of eventually being diagnosed with prostate cancer, making them ideal candidates for chemoprevention trials, reported the authors of a phase 3 study published in the Journal of Clinical Oncology online January 7, 2013.

“Treatment of prostate cancer results in the potential for significant long-term urinary and sexual dysfunction, making prevention of prostate cancer among men at increased risk most desirable if it can be achieved with acceptable toxicity and cost,” noted Samir S. Taneja, MD, of the Division of Urologic Oncology, New York University, Langone Medical Center, New York, NY, and colleagues. “Challenges in broad implementation of chemoprevention for prostate cancer include both selection of agent and defining an appropriate at-risk population.”

Noting that long-term risk of prostate cancer among men with isolated HGPIN on biopsy is not well defined—and optimal clinical management strategies controversial—the investigators “hypothesized that the high rate of coexistent cancer and the premalignant nature of HGPIN make these men ideal candidates for testing chemoprevention strategies.”

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A total of 1,590 men with isolated HGPIN (with or without coexistent atypical small acinar proliferation) and no prostate cancer on biopsy were randomly assigned to receive toremifene citrate 20 mg or placebo. During the 3-year multicenter trial, men underwent an annual biopsy until cancer was detected or the study ended.

Efficacy analysis included 1,467 men who had a least one on-study biopsy. “Baseline risk factors were evaluated to determine influence on cancer detection,” they reported.

Cancer was detected in 32.3% of the men who received treatment with toremifene and 34.7% who received placebo; no difference was observed in prostate cancer–free survival (P=0.39, log-rank test).

The 3-year Kaplan-Meier prostate cancer–free survival estimate was 59.5% (99% CI: 48.1%- 70.9%) in the treatment group and 54.9% (99% CI: 43.3%- 66.5%) in the placebo group.

“Exploration of baseline risk factors demonstrated no subset in which a risk reduction was observed,” Dr. Taneja noted. In the placebo group, 17.9% of men at risk at the beginning of year 1 were diagnosed with prostate cancer; it was 12.9% at the beginning of year 2 and 13.6% at the beginning of year 3.

An accompanying editorial noted, “So what should we recommend for a patient with PIN (prostatic intraepithelial neoplasia) on biopsy? We would discourage aggressive rebiopsy unless a risk assessment tool (such as the Prostate Cancer Prevention Trial Risk Calculator) suggests a high likelihood of a high-grade tumor that was missed on biopsy. In such a situation, it is reasonable to consider a high-fidelity magnetic resonance imaging study (eg, 3 Tesla magnetic resonance imaging with an endorectal coil) to identify regions of high risk for repeat biopsy.”