High grade prostatic intraepithelial neoplasia is likely a premalignant lesion of the prostate. Decreasing the frequency of high grade PIN may decrease the risk of prostate cancer. In the Prostate Cancer Prevention Trial we evaluated the impact of finasteride on the risk of a needle biopsy diagnosis of high grade prostatic intraepithelial neoplasia.
The Prostate Cancer Prevention Trial was a randomized, placebo controlled clinical trial that enrolled 18,882 men without evidence of prostate cancer, prostate specific antigen less than 3.0 ng/ml and normal digital rectal examination, and randomized them to 5 mg finasteride daily or placebo. Subjects were followed for 7 years with biopsy recommended for prostate specific antigen greater than 4.0 ng/ml, adjusted in the finasteride group to achieve an equal number of biopsy recommendations or for abnormal digital rectal examination. All cancer-free subjects were recommended to undergo biopsy after 7 years on study. We evaluated the diagnosis of high grade prostatic intraepithelial neoplasia with or without concomitant prostate cancer in these 2 study groups.
The number of men evaluable for high grade prostatic intraepithelial neoplasia was 4,568 in the finasteride group and 4,886 in the placebo group. High grade prostatic intraepithelial neoplasia alone was diagnosed in 276 men (6.0%) in the finasteride group vs 347 (7.1%) in the placebo group (RR 0.85, 95% CI 0.73-0.99, p=0.04). High grade prostatic intraepithelial neoplasia accompanied by prostate cancer was diagnosed in 144 men (3.2%) in the finasteride group vs 223 (4.6%) in the placebo group (RR 0.69, 95% CI 0.56-0.85, p=0.0004). Finasteride significantly decreased the overall risk of high grade prostatic intraepithelial neoplasia (alone and with cancer) from 570 cases (11.7%) in the placebo group to 420 (9.2%) in the finasteride group (HR 0.79, 95% CI 0.70-0.89, p<0.001).
Finasteride significantly decreased the risk of high grade PIN. This observation may explain how finasteride decreased prostate cancer in the Prostate Cancer Prevention Trial, supporting the notion that high grade prostatic intraepithelial neoplasia is a premalignant lesion of the prostate, and it provides new information relevant to the consideration of finasteride for prostate cancer prevention.
"According to Thompson et al. (2007), finasteride reduced, by 21%, the risk of high-grade prostatic intraepithelial neoplasia (HGPIN), the major precursor of prostate cancer, when compared to patients who received placebo control. However, different studies have highlighted the lower efficacy of finasteride on high-grade cancers (Thompson et al., 2007; Crawford et al., 2010). Lucia et al. (2007) suggested some Fig. 5. AR, ER-α, ER-β, VEGF, and endostatin immunoreactivities in the ventral prostate of mice from young group (a, d, g, j, m), senile group (b, e, h, n) and finasteride group (c, f, i, o). "
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate the structural and molecular effects of antiangiogenic therapies and finasteride on the ventral prostate of senile mice.
90 male FVB mice were divided into: Young (18weeks old) and Senile (52weeks old) groups; Finasteride group: Finasteride (20mg/kg); SU5416 group: SU5416 (6mg/kg); TNP-470 group: TNP-470 (15mg/kg,) and SU5416+TNP-470 group: similar to the SU5416 and TNP-470 groups. After 21days, prostate ventral lobes were collected for morphological, immunohistochemical and Western Blotting analyses.
The results demonstrated atrophy, occasional proliferative lesions and inflammatory cells in the prostate during senescence, which were interrupted and/or blocked by treatment with antiangiogenic drugs and finasteride. Decreased AR and Endostatin reactivities, and an increase for ER-α, ER-β and VEGF were seen in the senile group. Decreased VEGF and ER-α reactivities and increased ER-β reactivity were verified in the finasteride, SU5416 groups and especially in SU5416+TNP-470 group. The TNP-470 group showed reduced AR and ER-β protein levels.
The senescence favored the occurrence of structural and/or molecular alterations suggesting the onset of malignant lesions, due to the imbalance in the signaling between the epithelium and stroma. The SU5416+TNP-470 treatment was more effective in maintaining the structural, hormonal and angiogenic factor balance in the prostate during senescence, highlighting the signaling of antiproliferation via ER-β.
Life sciences 05/2014; 106(1). DOI:10.1016/j.lfs.2014.04.027 · 2.70 Impact Factor
"A number of studies have investigated possible therapies to lower the incidence of HGPIN or to decrease the rate of progression from HGPIN to prostate cancer . The Prostate Cancer Prevention Trial demonstrated that 7 years of treatment with daily finasteride decreased the incidence of HGPIN from 7.1 to 6.0% . Similarly, in the REDUCE trial, dutasteride reduced the incidence of HGPIN from 6.0 to 3.7% . "
[Show abstract][Hide abstract] ABSTRACT: High-grade prostatic intraepithelial neoplasia (HGPIN) has been established as a precursor to prostatic adenocarcinoma. HGPIN shares many morphological, genetic, and molecular signatures with prostate cancer. Its predictive value for the development of future adenocarcinoma during the prostate-specific antigen screening era has decreased, mostly owing to the increase in prostate biopsy cores. Nevertheless, a literature review supports that large-volume HGPIN and multiple cores of involvement at the initial biopsy should prompt a repeat biopsy of the prostate within 1 year. No treatment is recommended for HGPIN to slow its progression to cancer.
Korean journal of urology 05/2012; 53(5):297-303. DOI:10.4111/kju.2012.53.5.297
"In the PCPT, finasteride was effective in reducing the development of prostate cancer over a sevenyear period (prostate cancer was detected in 18.4 percent of men in the finasteride group compared to 24.4 of the placebo group). However, adenocarcinomas with a high-grade appearance were more common in the finasteride group (37 versus 22 percent) . "
[Show abstract][Hide abstract] ABSTRACT: High-grade intraepithelial neoplasia (HGPIN) is a lesion which is widely believed to be a precursor of prostatic adenocarcinoma. Correct morphologic identification of HGPIN and an understanding of how this diagnosis affects clinical management in the research setting are necessary as HGPIN is a premalignant lesion with many genetic alterations similar to prostate cancer, but is not yet invasive cancer. As such it is critical to differentiate between benign entities, HGPIN, and prostatic adenocarcinoma for experimental design and data interpretation. This review discusses HGPIN, clarifies the terminology used in pathology reports, and describes the clinical and research implications of this entity.
International journal of clinical and experimental pathology 02/2009; 2(4):327-38. · 1.89 Impact Factor
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