Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study.

Green tea catechins (GTCs) proved to be effective in inhibiting cancer growth in several experimental models. Recent studies showed that 30% of men with high-grade prostate intraepithelial neoplasia (HG-PIN) would develop prostate cancer (CaP) within 1 year after repeated biopsy. This prompted us to do a proof-of-principle clinical trial to assess the safety and efficacy of GTCs for the chemoprevention of CaP in HG-PIN volunteers. The purity and content of GTCs preparations were assessed by high-performance liquid chromatography [(-)-epigallocathechin, 5.5%; (-)-epicatechin, 12.24%; (-)-epigallocatechin-3-gallate, 51.88%; (-)-epicatechin-3-gallate, 6.12%; total GTCs, 75.7%; caffeine, <1%]. Sixty volunteers with HG-PIN, who were made aware of the study details, agreed to sign an informed consent form and were enrolled in this double-blind, placebo-controlled study. Daily treatment consisted of three GTCs capsules, 200 mg each (total 600 mg/d). After 1 year, only one tumor was diagnosed among the 30 GTCs-treated men (incidence, approximately 3%), whereas nine cancers were found among the 30 placebo-treated men (incidence, 30%). Total prostate-specific antigen did not change significantly between the two arms, but GTCs-treated men showed values constantly lower with respect to placebo-treated ones. International Prostate Symptom Score and quality of life scores of GTCs-treated men with coexistent benign prostate hyperplasia improved, reaching statistical significance in the case of International Prostate Symptom Scores. No significant side effects or adverse effects were documented. To our knowledge, this is the first study showing that GTCs are safe and very effective for treating premalignant lesions before CaP develops. As a secondary observation, administration of GTCs also reduced lower urinary tract symptoms, suggesting that these compounds might also be of help for treating the symptoms of benign prostate hyperplasia.

Immediate radical prostatectomy in patients with atypical small acinar proliferation. Over treatment?

PURPOSE: The term atypical small acinar proliferation (ASAP) has been proposed by pathologists to indicate foci of small atypical acini found in prostatic biopsies that have some but not all of the features of adenocarcinoma. We determined the incidence of ASAP at our institution and evaluated the role of immediate radical prostatectomy (RP) in these patients. MATERIALS AND METHODS: From January 2001 to December 2002, 1,327 patients underwent systematic transrectal prostate biopsies because of increased prostate specific antigen (PSA). Of the 1,327 patients 71 (5.3%) had suspicious cytokeratin negative lesions diagnosed as ASAP, as confirmed by a review pathologist. Mean patient age was 62 years and mean PSA was 8.48 ng/ml (range 5.6 to 19.6). Of the 71 patients 25 underwent pelvic bilateral lymphadenectomy and RP with a nerve sparing procedure immediately after the diagnosis of ASAP. A 79-year-old patient underwent transurethral resection of the prostate. A total of 45 patients were followed with PSA determination every 3 months and with prostatic mapping every 6 months (12 to 14 biopsies). RESULTS: All 25 patients (100%) with ASAP who underwent immediate RP had a final pathological diagnosis of adenocarcinoma, as confirmed by a review pathologist. Pathological stage was pT2a in 9 patients, pT2b in 8, pT2c in 6, pT3a in 1 and pT4 in 1. The Gleason sum was 2 to 6 in 21 patients, 7 in 2 and 8 in 2. One of the 25 patients had positive nodes (pT4N1G3). The pathological diagnosis in patients with transurethral resection was benign prostatic hyperplasia. Nine of the 45 patients who were followed were seen every 3 months for PSA determination because of age (older than 78 years). Of the 45 patients 23 (51.1%) underwent a second set of biopsies, which revealed adenocarcinoma in 6 of 23 (26%), benign prostatic hyperplasia in 6 (26%), ASAP again in 5 (21.7%), atypia in 4 (17.3%) and high grade PIN in 2 (8.6%). Six of 17 patients had a third set of biopsies (a total of 14 cores), including 3 with adenocarcinoma, 1 with ASAP and 2 with high grade PIN. Two of 45 patients (4.4%) did not undergo a second biopsy because of other malignancies. Four of 45 patients (8.8%) are awaiting a third or fourth biopsy. Ten of 45 patients (22.2%) were lost to followup. CONCLUSIONS: The results of our study confirm that immediate RP could be the treatment of choice in young patients with ASAP.

Apoptosis in prostate carcinoma before and after neoadjuvant therapy with LH-RH analog.

This study investigated apoptosis in prostate cancer before and after neoadjuvant treatment with LH-RH analog, demonstrating that this therapy induced high AI and bax and survivin overexpression, thus acting as a proapoptotic agent in prostate cancer. A statistically significant correlation was found between high AI and overexpression of bax protein after therapy. It is probable that this kind of therapy is deeply implicated in promoting the apoptotic intrinsic pathway.