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Localized prostate cancer. Relationship of tumor volume to clinical significance for treatment of prostate cancer.

BACKGROUND: Using the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute and American total mortality rates, the authors calculated the probability at birth of having a diagnosis of prostate cancer within a man's life to be 8.8% and then subtracted the incidence of microscopic Stage A cancers too small to ever be clinically significant. This gave a final probability of 8%. METHODS: Prostates were examined after 139 consecutive unselected cystoprostatectomies from patients with bladder cancers in whom it was unknown whether they had prostate cancer. Prostate cancer was found in 55 patients (40%); the volume of the largest cancer in each specimen was determined using histologic morphometry. The authors identified the 8% of these 139 cytoprostatectomy specimens with the largest volume of prostate cancer. RESULTS: The largest 11 of the 55 cancers represented 7.9% of the total 139 samples. These cancers ranged in volume from 0.5-6.1 ml, representing only 20% of all patients with prostate cancer. CONCLUSIONS: If the strong evidence is accepted that cancer progression is proportional to cancer volume, it was concluded that prostate cancers larger than 0.5 ml appear to correspond to the 8% of men who will be diagnosed with a clinically significant carcinoma, as derived previously. Conversely, those 80% of prostate cancers smaller than 0.5 ml probably are not likely to reach a clinically significant size in view of the long doubling time of this cancer.

Adult↗

The memorial anxiety scale for prostate cancer: validation of a new scale to measure anxiety in men with with prostate cancer.

BACKGROUND: The psychological difficulties facing men with prostate cancer are acknowledged widely, yet identifying men who may benefit from mental health treatment has proven to be a challenging task. The authors developed the Memorial Anxiety Scale for Prostate Cancer (MAX-PC) to facilitate the identification and assessment of men with prostate cancer-related anxiety. This scale consists of three subscales that measure general prostate cancer anxiety, anxiety related to prostate specific antigen (PSA) levels in particular, and fear of recurrence. METHODS: Ambulatory men with prostate cancer (n = 385 patients) were recruited from clinics throughout the United States. Prior to routine PSA tests, participants completed a baseline assessment packet that included the Hospital Anxiety and Depression Scale; the Distress Thermometer; the Functional Assessment of Cancer Therapy Scale, Prostate Module; and measures of role functioning, sleep, and urinary functioning. PSA values from the last three tests also were collected. Follow-up evaluation was completed within 2 weeks after patients learned of their PSA test result using a subset of these scales. RESULTS: Analysis of the MAX-PC revealed a high degree of internal consistency and test-retest reliability for the total score and for the three subscales, although reliability was somewhat weaker for the PSA Anxiety Scale. Concurrent validity was demonstrated by correlations between the MAX-PC and measures of anxiety. Overall changes in PSA levels were correlated only modestly with changes in MAX-PC scores (correlation coefficient, 0.13; P = 0.02). CONCLUSIONS: The MAX-PC appears to be a valid and reliable measure of anxiety in men with prostate cancer receiving ambulatory care.

Anxiety↗

A population-based survey of prostate-specific antigen testing among California men at higher risk for prostate carcinoma.

BACKGROUND: Despite the lack of evidence demonstrating a survival benefit from prostate-specific antigen (PSA) screening, its use has become widespread, organizations have encouraged physicians to discuss early detection of prostate carcinoma, and two higher risk groups have been recognized. In the current study, the authors examined whether African-American men and men who had a family history of prostate carcinoma underwent PSA testing preferentially, and patterns of test use were examined according to age, race, and other factors. METHODS: Data regarding self-reported PSA test use in the past year among men age 50 years and older without a history of prostate carcinoma (n = 8713 men) were analyzed from the 2001 California Health Interview Survey. RESULTS: The overall rate of PSA use was 43.0%. Older age, higher socioeconomic status, having a usual source of healthcare, and a family history of prostate carcinoma were the strongest predictors of testing. Higher risk African-American men age 50 years and older were no more likely to be tested than white men. Men at higher risk who had a family history of prostate carcinoma were more likely to have been tested than men who had no such family history. CONCLUSIONS: Rates of PSA use among higher risk men who had a family history of prostate carcinoma were higher compared with the rates among men without such a family history. However, PSA testing rates among higher risk African-American men were no different than the rates among lower risk white men, suggesting that some risk factors for prostate carcinoma (but not others) are associated with preferential testing. Testing in all groups was associated with access to care variables, highlighting the importance of removing barriers to preventive healthcare services.

Black or African American↗

Variations of components of the plasminogen activation system with the cell cycle in benign prostate tissue and prostate cancer.

BACKGROUND: Components of the fibrinolytic system are involved in tumor cell invasion and metastasis. Previous investigations suggested a cell cycle-dependent expression of urokinase-type plasminogen activator (u-PA) in epithelial cells. In order to determine a correlation of cell cycle phases with the fibrinolytic system, we investigated the expression of u-PA, tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor type 1 (PAI-1) in normal and tumor-containing prostate extracts and analyzed a possible relationship with flow cytometry-determined proliferative activity of the samples. Cell cycle phases were correlated with fibrinolytic parameters in prostate tissue. METHODS: Samples were obtained from patients undergoing radical prostatectomy for prostate cancer and separated into two portions for DNA analysis and the detection of u-PA, t-PA, and PAI-1. Flow cytometric analysis was performed according to the Vindelov technique. The concentrations of u-PA, t-PA, and PAI-1 were determined from tissue extracts after homogenization by an enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: Correlations of u-PA and t-PA expression with the frequency of G0/G1, S, G2M, S-phase fraction (SPF), and proliferation index (PI) for normal prostate and prostate cancer revealed no significant correlation. The only significant finding was observed in normal tissue revealing a positive correlation between PAI-1 expression and G0/G1 and a negative correlation with S-phase, SPF, and PI. No dependence of PAI-1 expression on different cell phases was found in prostate cancer. Furthermore, no significant correlation of u-PA, t-PA, and PAI-1 with cell cycles in organ-confined ( or = pT3a) tumors was found. No significant correlation in prostate cancer of components of the fibrinolytic system differentiated according to tumor grade or perineural tumor infiltration and cell cycle analysis was found. Only in highly differentiated G1 (Gleason 2-4) cancer, u-PA had a significant positive correlation with G2M-phase. CONCLUSION: Absence of a correlation between levels of components of the fibrinolytic system and cell cycle phases suggests that the reported association between increases of some of these components and aggressive biological behavior of prostate cancer is secondary to non-cell cycle-related mechanisms.

Cell Cycle↗

Intermediate cells in normal and malignant prostate epithelium express c-MET: implications for prostate cancer invasion.

BACKGROUND: Analysis of keratin (K) expression discriminates luminal (K18) and intermediate (K5/18) cells in prostate carcinoma, while basal (K5/14) cells are absent. Intermediate cells have been proposed as targets of malignant transformation in prostate cancer and precursors of androgen-independent tumor progression. We demonstrate localization of hepatocyte growth factor (HGF) receptor c-MET in intermediate cells in both normal and malignant prostate epithelium. METHODS: Receptor localization was analyzed using triple staining for c-MET, K5, K14, and K18. The percentage of strongly c-MET positive cells was determined in 15 prostate cancer patients undergoing androgen-deprivation and 14 patients without neo-adjuvant treatment. Effects of HGF were investigated on prostate cancer cell line DU145. RESULTS: c-MET expression in non-malignant epithelium was strong in intermediate cells absent in differentiated cells, and heterogeneous in basal cells. In prostate cancer, intermediate cells displayed high c-MET levels coupled with mild expression in differentiated cells. During androgen-deprivation, 7.6% of tumor cells revealed high c-MET expression compared to 1.7% without treatment (P = 0.02). Matrigel penetration of DU145 was 8.2 +/- 1.7 mm(2) after HGF stimulation compared to 3.6 +/- 2.4 mm(2) in controls (P < 0.02). CONCLUSIONS: Intermediate cells in normal and malignant prostate epithelium express high c-MET levels, indicating that they are prone to stromal invasion in prostate carcinoma.

Androgens↗

Expression of somatostatin receptor subtypes 2 and 4 in human benign prostatic hyperplasia and prostatic cancer.

BACKGROUND: The presence of receptor subtypes for the inhibitory peptide somatostatin in prostatic tissue has been a controversial issue with conflicting reports. To elucidate whether prostatic epithelial cells express mRNA for somatostatin receptor (SSTR) subtype 2 and 4, we have investigated the localization of SSTR2 and SSTR4 transcripts in prostatic tissues by in situ hybridization. METHODS: Nonradioactive in situ hybridization was performed with specific fluorescein-labeled SSTR2 and SSTR4 riboprobes on consecutive sections of benign prostatic hyperplasia (BPH) and prostate cancer tissues. RESULTS: We report, for the first time, tissue localization of SSTR2 and SSTR4 mRNA in BPH and malignant cells of human prostate. Hybridization signals for SSTR4 mRNA transcripts were confined to the prostatic epithelium (12 of 16 BPH cases, and in 12 of 13 carcinoma cases), whereas SSTR2 transcripts were predominantly localized in the stromal compartment but also were detectable in epithelial cells in a significant number of specimens (11 of 17 BPH cases, and in 12 of 14 carcinoma cases). Furthermore, the staining intensity for SSTR2 and SSTR4 transcripts is stronger in malignant cells compared with adjacent BPH epithelium. CONCLUSION: The data presented suggest that the expression of SSTR2 and SSTR4 transcripts is up-regulated in malignant cells and that not only SSTR2 agonists, but also compounds targeting the SSTR4 subtype may have a potential role in the treatment of prostate cancer.

Carcinoma↗

Differential expression of the estrogen receptor beta (ERbeta) in human prostate tissue, premalignant changes, and in primary, metastatic, and recurrent prostatic adenocarcinoma.

BACKGROUND: Estrogen signaling mediated by the estrogen receptor beta (ERbeta) has potential implications in normal and abnormal prostate growth. Few studies have addressed this issue in human prostate tissue leaving conflicting results on the immunolocalization of the ERbeta in benign and neoplastic lesions. METHODS: Using a new monoclonal antibody, the current study reports on the differential expression of the ERbeta in tissue sections from 132 patients with prostate cancer. RESULTS: The prostatic epithelium expressed the ERbeta extensively in secretory luminal cell types and at lower levels in basal cells. Atrophic changes of the peripheral zone (PZ) were more immunoreactive than hyperplastic lesions of the transition zone (TZ). When compared with glandular tissue of the PZ, high-grade prostatic intraepithelial neoplasia (HGPIN) revealed decreased levels of the ERbeta in 30 of 47 cases and was unreactive in six lesions. In informative cases with suitable internal controls, all primary tumors (n = 60), lymph node (n = 7), and bone metastases (n = 5) expressed the ERbeta at variable degree. No correlation was found between the ERbeta status, the primary Gleason grade (P = 0.254), and the pathological stage (P = 0.157). Recurrent adenocarcinoma revealed markedly decreased levels in 15 of 40 cases and was ERbeta negative in five recurrent lesions. CONCLUSIONS: The secretory epithelium is a major target of ERbeta-mediated estrogen signaling in the human prostate. Its downregulation in HGPIN is consistent with chemopreventive effects that the ERbeta may exert on the prostatic epithelium. The continuous expression of the receptor protein at significant levels in untreated primary and metastatic adenocarcinoma indicates that these tumors can use estrogens through an ERbeta-mediated pathway. The partial loss of the ERbeta in recurrent tumors after androgen-deprivation may reflect the androgen-dependence of ERbeta gene expression in human prostate cancer.

Adenocarcinoma↗

PRAC2: a new gene expressed in human prostate and prostate cancer.

BACKGROUND: The database of human Expressed Sequence Tags was previously used to identify PRAC (Prostate 47:125-131, 2001), a novel gene specifically expressed in human prostate, prostate cancer, rectum, and distal colon. In this report, we have identified PRAC2, another gene with a similar expression pattern that is located adjacent to the original PRAC gene on chromosome 17q21.3. METHODS: Using a computer-based analysis, a cluster of sequence homologous ESTs was identified that is mainly derived from human prostate cDNA libraries. The tissue specificity was examined by multiple tissue RNA dot blots and RT-PCR. The PRAC2 transcript and protein were identified using Northern blot analysis, RACE-PCR, primer extension, and Western blots. RESULTS: PRAC2 encodes a 564 nucleotide RNA found in prostate, rectum, distal colon, and testis. Weak expression was also found in placenta, peripheral blood leukocytes, skin, and in two prostate cancer cell lines: LNCaP and PC-3. The transcript seems to encode a 10.5-kDa nuclear protein. The PRAC2 gene is located on chromosome 17 at position 17q21, between the Hoxb-13 gene and the recently discovered PRAC gene. CONCLUSIONS: Because of the higher expression of PRAC2 in prostate and its proximity to Hoxb-13, PRAC2 may have a function in prostate growth and development.

Amino Acid Sequence↗

GDEP, a new gene differentially expressed in normal prostate and prostate cancer.

BACKGROUND: The database of human expressed sequence tags (dbEST) is a potential source for the identification of tissue specific genes. The database contains sequences that originate from cDNA libraries from different tissues cell types and tumors. METHODS: Computer based analysis identified a cluster of sequence homologous ESTs, containing ESTs derived only from human prostate cDNA libraries. The tissue specificity was examined by multiple tissue RNA dot blots and RT-PCR. The new RNA transcript was characterized using northern blot analysis, RACE-PCR, and a ribonuclease protection assay. RESULTS: We have identified a gene differentially expressed in prostate using EST database analysis and experimental studies. We name the gene GDEP for gene differentially expressed in prostate. The major GDEP transcript is about 520 bp long. GDEP RNA was detected in nine prostate tissue samples, four normal and five cancer. Expression in prostate epithelial cells was established by in situ hybridization. Weak expression was detected in the prostate cancer cell line LNCaP. In vitro transcription/translation indicate that the RNA encodes a small 34 amino acid protein. The major transcript consists of two exons with one large intron (> 15 kb). The GDEP gene was mapped to chromosome 4q21.1 by radiation hybrid mapping. CONCLUSIONS: Our data proves that tissue specific genes can be identified by EST database mining. The prostate specificity of GDEP expression indicates that GDEP may be useful in the diagnosis or treatment of prostate cancer. Published 2001 Wiley-Liss, Inc.

Amino Acid Sequence↗

Decreasing age at prostate cancer diagnosis over successive generations in prostate cancer families.

BACKGROUND: The decline in age at prostate cancer diagnosis over the past decade is partially attributable to prostate specific antigen (PSA) screening. We examined age at diagnosis over successive generations within prostate cancer families. METHODS: Families with at least two affected men were selected from the University of Michigan Prostate Cancer Genetics Project. The 1,345 individuals from 489 families were grouped into three generations. RESULTS: Risk of prostate cancer diagnosis at a given age was estimated to increase 1.31 (95% CI: 1.13-1.51) times from one generation to the next. Among men diagnosed prior to the PSA era, inferences were similar (hazard ratio = 1.28, 95% CI: 0.97-1.68). No maternal versus paternal disease transmission effect was observed. CONCLUSIONS: Age at prostate cancer diagnosis was observed to decrease over successive generations in families from an ongoing familial prostate cancer study. This finding, if confirmed, may have important implications for familial prostate cancer risk assessment.

Age Distribution↗

Allelotyping analysis at chromosome 13q of high-grade prostatic intraepithelial neoplasia and clinically insignificant and significant prostate cancers.

BACKGROUND: Loss of heterozygosity (LOH) at 13q is one of the most common chromosomal alterations in high-stage prostate cancer, yet little is known about genetic changes in earlier-stage prostate cancer. METHODS: We used five microsatellite markers at 13q14, 21, and 33 to compare LOH frequencies in 51 lesions of high-grade prostatic intraepithelial neoplasia (HGPIN), 21 cases of incidental prostate cancers (IPCs), 31 cases of latent prostate cancers (LPCs), and 102 cases of clinical prostate cancers (CPCs). RESULTS: The frequency of LOH at 13q with at least 1 marker was 0%, 38%, 56%, and 49% in HGPIN, IPCs, LPCs, and CPCs, respectively. No statistically significant difference was found between the types of prostate cancer. Allelic loss at 13q14 was significantly more frequent in pT4 tumors than in earlier-stage tumors (P=0.011). CONCLUSIONS: Allelic loss at 13q is not only an important event in the metastasis of prostate cancer, but also associated with the initiation of the tumor.

Alleles↗

Proliferative responses of cultured rat prostate and human benign prostatic hyperplasia.

The proliferative responses of rat prostate and human benign prostatic hyperplasia have been followed in organ culture using [125I] iododeoxyuridine uptake to monitor DNA synthesis. In serum-free cultures, testosterone induced a marked increase in DNA synthesis (three-fold) in 4- to 6-month-old rat prostates at concentrations of 4 x 10(-9) to 4 x 10(-6) M, whereas in greater than 12-month-old rat prostates the response was less marked. Human benign prostatic hyperplasia also showed an increased uptake at similar testosterone concentrations and of a similar magnitude to the response of greater than 12-month-old rat prostates. At 10(-5) M DNA synthesis was markedly suppressed in cultures of both rat and human prostate. The proliferative response of human benign prostatic hyperplasia increases up to days 3 to 4 in culture and then declines in both control and hormone-treated groups and may represent repair processes which appear to be hormone dependent.

Animals↗

Prostatic structure and function in relation to the etiology of prostatic cancer.

In this paper, studies by a large series of independent investigators are reviewed with regard to the basic structure and function of the prostate in an attempt to examine their relationship to prostatic cancer etiology. These studies demonstrate that the functional activities of the prostate involve secretion, transport, and reabsorption of a variety of materials into and out of the glandular lumen and that these activities are directly related to the basic structural organization of the gland. These functional activities are constantly occurring in the prostate even under basal (ie, nonejaculating) conditions. Due to these functional activities, the prostatic fluid in the glandular lumen is a complex mixture of a variety of components derived, not only from the synthetic activity of the glandular epithelial cells of the gland itself, but also from the blood serum. The levels of these components are continuously modulated, not only by the frequency of active ejaculation, but also, under basal conditions by the continuous interaction with the glandular prostatic cells lining the acinar lumen and ducts. A concept is presented that the initiation and/or promotion of prostatic carcinogenesis may well involve the chronic modulation/interaction of the prostatic glandular cells with their lumenal fluid.

Acid Phosphatase↗

Effect of prostatic inhibin peptide (PIP) on prostate cancer cell growth in vitro and in vivo.

Prostatic inhibin peptide (PIP), is a 94 amino acid protein which is secreted by the prostate gland in an androgen-independent manner. Previously, it has been demonstrated that PIP appears to inhibit follicle-stimulating-hormone (FSH) secretion by the pituitary and prostate glands. In vitro, the Dunning R3327 rat prostate cancer cell line MAT-LyLu (MLL) cells and the human prostate cancer cell line PC-3, are stimulated to grow in response to exogenous FSH and these effects are blocked by PIP. In vivo, PIP inhibits the growth of the highly metastatic MLL prostate cancer cell line. A comparison of hormone levels in control and PIP-treated rats demonstrates a significant inhibition of FSH in treated animals. It appears that, in vivo, PIP may inhibit prostate cancer growth by inhibiting FSH. PIP may represent a novel hormonal treatment for prostate cancer.

Adenocarcinoma↗

Anatomy of the prostate and distribution of early prostate cancer.

Many of the difficulties in understanding diseases of the prostate have arisen through poor understanding of the anatomy of the prostate. The recent description of histologically separate zones in the prostate has been an important advance, allowing evaluation of separate cancers arising in the transition and peripheral zones of the prostate. While the majority of cancers sampled at transurethral resection of the prostate (TURP) are of transition zone origin, most of these prostates contain separate cancers in the peripheral zone. The peripheral zone cancers have a higher grade-to-volume ratio and are more frequently associated with histological features of progression (extracapsular extension, seminal vesicle invasion) than transition zone cancers. Furthermore, peripheral zone cancers are frequently associated with prostatic intraepithelial neoplasia, in contrast to transition zone cancers. These findings suggest a greater biological activity for cancers arising in the peripheral zone. The majority of cancers detected by digital rectal examination are of peripheral zone origin. While associated transition zone cancers are less frequently present than in TURP sampled prostates, a similarly high association of peripheral zone cancers with histological indicators of biological activity is seen. DNA ploidy analysis of separate foci in radical prostatectomy specimens confirms a significantly higher rate of non-diploidy in cancers of peripheral zone origin, some of very small volume, which further suggests a greater biological activity compared to transition zone cancers.

DNA, Neoplasm↗

Studies on glutathione metabolism in ventral prostate and chemically induced prostatic carcinoma in rats.

Glutathione content and the activity of glutathione reductase were examined in ventral prostate and chemically induced 11095 squamous-cell prostatic carcinoma in rats. Castration produced a significant reduction in the levels of reduced (GSH) and oxidized (GSSG) glutathione and glutathione reductase activity in the prostate. Replacement of testosterone (50 mg/kg) daily for 7 days to castrated animals elevated the reduced glutathione level and the activity of glutathione reductase almost to normal limits. Squamous-cell carcinoma was implanted in castrated and intact animals. Tumor growth in normal rats produced a decrease of almost 30% in the weight of the ventral prostate at 21 days post-implantation, although the glutathione levels remained unaffected. Much greater activity of glutathione reductase was detected in the tumor in comparison to the values noted for the normal tissue. The tumor also showed significantly higher values for the GSH/GSSG ratio. No apparent difference could be found in the rate of the growth of tumors whether implanted in normal or castrated animals. The levels of reduced and oxidized glutathione and glutathione reductase activity also seemed identical in tumors obtained from both groups of animals. Administration of testosterone (50 mg/kg) or beta-estradiol (2 mg/kg) daily for 11 days to tumor-bearing castrated animals did not alter the levels of glutathione and glutathione reductase activity. A significantly higher level of blood reduced glutathione was found in tumor-bearing rats in comparison to that seen for the normal subjects. Our results demonstrate that androgen depletion and replacement therapy influence the metabolism of glutathione in rat ventral prostate. Squamous-cell carcinoma of the prostate appears to differ from the normal tissue with respect to the observed androgen effects. There is dissimilarity in the metabolism of glutathione in the two tissues since greater activity of glutathione reductase and lower values of reduced glutathione were seen in the tumor as compared to those of the ventral prostate. Treatment with beta-estradiol, an antiprostatic agent, does not seem to influence the growth or glutathione metabolism of squamous-cell carcinoma of the prostate. The observed changes in blood glutathione levels might prove to be useful as an index of rapid growth of the neoplastic tissue.

Animals↗

Keratin profiles in normal/hyperplastic prostates and prostate carcinoma.

Immunoreactivities in 25 cases of prostatic adenocarcinoma and 10 normal/hyperplastic prostates were investigated in methacarn-fixed, paraffin-embedded serial sections using a panel of nine anti-keratin monoclonal antibodies (mAbs); 34 beta E12, CK8.12, 312C8-1, CK4.62, RPN1165, RPN1162, 35 beta H11, CK5, M20, and one of anti-actin mAb, HHF35. In normal/hyperplastic prostates, RPN1162, 35 beta H11, CK5 and M20 stained luminal cells without staining basal cells, and 34 beta E12, CK8.12 and 312C8-1 stained basal cells but not luminal cells. Other mAbs, CK4.62 and RPN1165, stained basal cells as well as luminal cells. All of the mAbs labelling luminal cells stained cancer cells with variable frequencies in a manner unrelated to the grade of tumour differentiation. Of the prostate cancer cases 92% were scored positive with M20, 84% with 35 beta H11, 80% with CK5, 68% with CK4.62, 60% with RPN1165 and 4% with RPN1162. However, basal cell-specific keratins labelled with 34 beta E12, CK8.12 and 312C8-1 were totally negative in the cancer cells. HHF35 showed no labelling in normal, hyperplastic or neoplastic epithelial cells of the prostate. Our findings indicate that the major part of the cells of prostatic adenocarcinomas have keratin phenotypes similar to luminal cells but not basal cells, and that no myoepithelial differentiation can be detected in epithelial cell of the prostate. Thus, mAbs for keratins facilitate the identification of epithelial cell phenotypes in normal, benign and malignant conditions of the prostate.

Adolescent↗

High-grade prostatic intraepithelial neoplasia and prostate cancer risk reduction.

High-grade prostatic intraepithelial neoplasia (PIN) is the earliest accepted stage in carcinogenesis, possessing most of the phenotypic and biochemical changes in cancer without invasion of the basal membrane of the acini. The support for high-grade PIN as the main premalignant lesion of prostate cancer is based on several lines of evidence derived from prostate cancer animal models, epidemiological, morphological, genetic, and molecular studies. The incidence of high-grade PIN averages 9% (range 4-16%) in prostate biopsies, representing 115,000 new cases of high-grade PIN diagnosed each year in the United States. Performing saturation prostate biopsies to rule out any coexistent prostate cancer followed by every 3-6 month serial repeated prostate biopsies is currently the only way in which to manage patients found to have high-grade PIN. Medical therapy for high-grade PIN may easily become the mainstay treatment for high-grade PIN. Treatment of high-grade PIN appears to be of clinical benefit notwithstanding the potential for prostate cancer risk reduction. These clinical benefits would reduce morbidity, enhance quality of life, delay surgery or radiation, and increase the interval for surveillance requiring invasive procedures.

Animals↗