Prostatic intra-epithelial neoplasia

TH. H. van der Kwast1, A. Vis1,2 and R.F. Hoedemaker1

Dept. of Pathology1 and Urology2, Erasmus Medical Center, Rotterdam, The Netherlands

Aim: High grade prostatic intra-epithelial neoplasia (PIN) is considered as the most common precursor lesion of peripheral zone prostatic adenocarcinomas. Since prostate cancers initially are highly sensitive to androgen deprivation therapy, it was anticipated that chemoprevention of prostate cancer could be achieved by (low dose) endocrine therapy of men with isolated PIN. The natural course of PIN under conditions of low androgens is not well-established and literature data on the incidence of isolated PIN vary considerably (Vis and Van der Kwast, BJU International 88: 147-151, 2001). Methods: In a population screened for prostate cancer the frequency of isolated PIN was determined. Repeat biopsies of these men with isolated PIN within 6 weeks excluded the presence of a significant concomitant prostate cancer. To study the effect of androgen deprivation on PIN, prostatectomy specimens of 40 patients with clinically localized prostate cancer, randomized to 3 months (n=18) and 6 months (n=22) of neoadjuvant combined androgen blockade were examined for PIN. Results: Initial studies, on prostatic needle biopsies of men referred to urologic clinics, demonstrated a surprisingly high percentage of isolated PIN (without accompanying prostate cancer), with figures up to 16%. Data on isolated PIN from the Rotterdam section of the ERSPC, revealed an incidence of about 1% in men between 55 and 75 years, using a PSA cut-off value of 3.0 ng/ml for systematic sextant needle biopsies. More importantly, repeat biopsies in these men within 6 months led to the discovery of prostate cancers in about 12% of the cases. This is within the background levels of prostate cancers detected in men with a previous benign outcome of their biopsies. The differences in reported frequency of PIN and its clinical impact can most likely be attributed to a difference in population selected and in biopsy procedure. After total androgen blockade therapy the proportion of prostatectomies with PIN dropped from 72% at 3 months to 59% at 6 months. This difference is not statistically significant. The number of glands involved by PIN decreased from a median number of 19 at 3 months to 7 glands at 6 months (p = 0.17). In three of the five prostatectomy specimens of patients whose androgen deprivation was stopped one week or more prior to surgery, foci of high grade PIN were noted, showing the typical prominent nucleoli similar to those observed in untreated specimens. Conclusions: The incidence of isolated PIN in an asymptomatic population of men aged between 55 and 75 years is low and the clinical significance of its finding is limited. Although androgen deprivation leads to a reduced extent of lesions with the morphology of PIN this effect is reversible and prolonged treatment with total androgen blockade does not eradicate PIN.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Risk Assessment & Prognosis.