Discrimination of men with prostate cancer from those with benign disease by measurements of human glandular kallikrein 2 (HK2) in serum.

PURPOSE: To investigate the clinical value of measuring human glandular kallikrein 2 (hK2) compared with free and total prostate specific antigen (PSA-F and PSA-T) in serum from patients with prostate disease. MATERIALS AND METHODS: Serum from healthy controls, from men with benign prostate hyperplasia (BPH), clinically localized prostate cancer (PCa), and advanced PCa were analyzed for hK2 (using an in-house-research assay with detection limit of 0.05 ng./mL and <0.1% cross-reaction with PSA) and for PSA-F and PSA-T (using the Dual Prostatus assay from EG&G Wallac). RESULTS: HK2 concentrations were <0.05 ng./mL in 50/50 healthy volunteers but significantly higher (p <0.0001) and > or =0.05 ng./mL in 28/54 (52%) patients with BPH. In comparison to these men, the hK2 levels were significantly higher (p <0.0001, median 0.085 ng./mL) and > or =0.05 ng./mL in 100/136 (74%) men with clinically localized PCa. Compared with localized PCa, the hK2 levels were significantly higher (p <0.0001, median 0.57 ng./mL) and > or =0.05 ng./mL in 55/57 (96%) patients with advanced PCa. The median hK2 levels ranged from 1.3 to 1.6% of those of PSA-T in all three patient groups, whereas percent hK2/PSA-F and hK2 x PSA-T/PSA-F levels were significantly higher in cancer patients compared with those with BPH. In the discrimination of clinically localized PCa from BPH, hK2 x PSA-T/PSA-F gave the largest area under the receiver operating curve (AUC = 0.81) and significantly (p = 0.025) larger AUC than PSA-T alone (0.70). Further, at 95% sensitivity there was significant gain in specificity, and at specificity levels of 90 to 95% there was significant gain in sensitivity using the measurements of PSA-T+PSA-F+hK2 compared with analysis of PSA-T and/or percent free PSA. CONCLUSIONS: Discrimination of patients with benign prostate disease from those with prostate cancer was significantly enhanced using measurements of hK2 in addition to those of PSA-T and PSA-F. Percent hK2/PSA-F was higher in PCa than in BPH, a phenomena not yet understood.

Prostate specific antigen: a decade of discovery--what we have learned and where we are going.

PURPOSE: Many advances have occurred during the last decade in the clinical use of prostate specific antigen (PSA) for detecting, staging and monitoring prostate cancer. We review the clinical usefulness and limitations of serum PSA as a tumor marker of prostate cancer. MATERIALS AND METHODS: The English language literature was reviewed with respect to the major contributions and limitations of PSA in present clinical practice. RESULTS: Although controversial, age specific PSA reference ranges can improve the sensitivity for prostate cancer detection in young men and the specificity in older men. Percent free PSA improves the specificity for prostate cancer detection in men with PSA values between 4 and 10 ng./ml., and a PSA density of greater than 0.15 may better distinguish benign prostatic hyperplasia from prostate cancer. PSA velocity can improve the ability to detect prostate cancer when 3 serial PSA values are measured during a 2-year period. For prostate cancer staging PSA is most useful combined with clinical stage and Gleason score in multivariate analysis. Percent free PSA may prove useful for staging prostate cancer but further clinical trials are needed to determine its clinical usefulness. PSA is the most clinically useful means to monitor disease recurrence after treatment of prostate cancer. With ultrasensitive PSA assays it is now possible to increase the lead time for detection of disease recurrence by several months. CONCLUSIONS: During the last decade much of the focus has been on improving the ability of this tumor marker to detect prostate cancer. PSA remains the best and most widely used tumor marker in urology today.

Have complication rates decreased after treatment for localized prostate cancer?

PURPOSE: The American Urological Association Prostate Cancer Clinical Guidelines Panel reviewed 12,501 publications on prostate cancer from 1955 to 1992 to determine whether the complication rates of external beam radiation therapy, interstitial radiotherapy and radical prostatectomy have decreased. MATERIALS AND METHODS: Complications reported in at least 6 series, study duration and sample sizes were extracted. Year specific study weighted mean patient ages and complication rates were computed. Regression analysis was performed of the study year on weighted mean patient age and complication rate. RESULTS: Study year had a significant effect on mean patient age and rate of the majority of complications examined. Data indicated a gradual increase in study patient age and a simultaneous decrease in complications from 1960 to 1990. CONCLUSIONS: Complication rates in the treatment of localized prostate cancer have decreased during the last 20 to 40 years. This decrease occurred despite evidence that the average age of treated patients had increased during the same period.

Reference ranges for serum prostate-specific antigen in black and white men without cancer.

OBJECTIVES: To determine the age- and race-specific prostate-specific antigen (PSA) distributions in healthy men in central South Carolina and to compare these to data from other studies. METHODS: Two thousand ninety-two black men aged 40 to 69 years and white men aged 50 to 69 years from the general population in 11 counties of central South Carolina participated in a prostate cancer educational program. Seventy-two percent of the participants were black-about double the proportion in the general population-and 63% of the men (1319 of 2092) subsequently obtained a PSA determination from their own physician. The distribution of serum PSA was compared with distributions from the Olmsted County study and from the Walter Reed Army Medical Center/Center for Prostate Disease Research study. RESULTS: Older men without cancer had higher PSA levels. Regression analyses yielded an associated increase of about 3.3% per year. Reference ranges for normal PSA in men without cancer (based on their sample 95th percentiles) were zero to 1.9, 3.8, and 5.7 ng/mL in black men aged 40 to 49, 50 to 59, and 60 to 69 years, and zero to 2.7 and 4.9 mg/mL in white men aged 50 to 59 and 60 to 69 years, respectively. CONCLUSIONS: Reference ranges for normal serum PSA levels should take into account the population from which they are derived and to which they will be applied. Reference ranges that are useful in the general population can differ from those that are appropriate in a hospital setting. For the general population in central South Carolina, reference ranges for serum PSA levels are lower than previously published reference ranges, particularly among black men.

Understanding artificial neural networks and exploring their potential applications for the practicing urologist.

Artificial neural networks (ANNs) are complex mathematical models that are distantly based on the human neuronal structure. They are capable of modeling elaborate biologic systems without making assumptions based on statistical distributions. Preliminary work has been reported on their application in urology. The initial results have been promising, particularly as an additional tool in the detection of early prostate cancer using the ProstAsure Index, which has been the most extensively studied urologic ANN to date. We review the basic concepts behind ANNs and examine currently existing and potential future applications of this new dynamic technology both in urology and in general clinical medicine.

Screening digital rectal examination and prostate cancer mortality: a population-based case-control study.

OBJECTIVES: Although digital rectal examination (DRE) for the detection of prostate cancer has been recommended by many professional groups and has become part of the general physical examination, no randomized clinical trial has demonstrated the efficacy or effectiveness of this practice. We conducted a population-based case-control study to evaluate the association between DRE and prostate cancer mortality. METHODS: With the resources of the Rochester Epidemiology Project, all 173 men who died of prostate cancer in Olmsted County from 1976 to 1991, who were resident at the time of diagnosis, were identified. For each case, two control patients were drawn from the population, matched for residence at the time of diagnosis in the case, birth date, and duration of medical record in Olmsted County. Trained nurse abstractors reviewed the community medical records for up to 10 years before the date of diagnosis in the case for mention of DRE and specific findings associated with each mention. RESULTS: Case subjects were less likely than control subjects to have had any DRE in the 10 years before diagnosis (matched odds ratio [OR] = 0.51; 95% confidence interval [CI] = 0.31, 0.84). When limited to DREs without mention of signs or symptoms that might raise suspicion of prostate cancer, the association was even stronger (OR = 0.31; 95% CI = 0.19, 0.49). Adjustment for educational attainment, marital status, and comorbid conditions did little to alter the associations. CONCLUSIONS: These results demonstrate a strong inverse association between DRE and prostate cancer mortality. If further research concludes this association to be causal, screening DREs may have prevented as many as 50% to 70% of deaths due to prostate cancer that might have occurred in the absence of screening.

Prostate cancer screening and beliefs about treatment efficacy: a national survey of primary care physicians and urologists.

PURPOSE: To describe practice patterns and beliefs of primary care physicians and urologists regarding early detection and treatment of prostate cancer. SUBJECTS AND METHODS: National probability samples of primary care physicians (n=444) and urologists (n=394) completed mail survey instruments in 1995. Physicians were asked about their use of prostate-specific antigen (PSA) testing for men of different ages and their beliefs about the value of radical prostatectomy, external-beam radiation therapy, and watchful waiting for men with differing life expectancies. RESULTS: Most primary care physicians report doing PSA tests during routine examination of men older than 50 years of age. The majority say they continue to do them on patients over 80 years and to refer men with abnormal values for biopsy. In contrast, only a minority of urologists would recommend PSA tests or biopsy for abnormal values for men over 75 years of age. More than 80% of primary care physicians and urologists doubt the value of radical prostatectomy for men with < 10 years of life expectancy; more primary care physicians than urologists see probable survival benefit in radiation therapy for patients with life expectancy < 10 years (48% versus 36%) or > 10 years (67% versus 53%). Thirteen percent of primary care physicians and only 3% of urologists consider watchful waiting to be as appropriate as aggressive therapy for men with > 10 years of life expectancy. CONCLUSIONS: Primary care physicians are more aggressive about PSA testing and referral for biopsy than most urologists recommend. Both groups recommend PSA testing and believe that aggressive treatment is more beneficial than existing evidence indicates.

Transurethral needle ablation of the prostate: a minimally invasive treatment for symptomatic benign prostatic hyperplasia.

Transurethral needle ablation of the prostate, a relatively new minimally invasive treatment modality for patients with bladder outlet obstruction attributable to an enlarged prostate gland, has undergone extensive evaluation by numerous investigators worldwide. The results to date indicate that needle ablation is safe and effective for relieving symptoms in patients with benign prostatic hyperplasia, and the effect has been demonstrated to be durable for at least 2 years. Nevertheless, additional investigations with longer follow-up data are needed to address the important issues of extended durability (5 to 10 years) and biophysiologic mechanism of action. Comparisons between transurethral needle ablation of the prostate and transurethral resection of the prostate (TURP) have revealed that the subjective and objective measures of response are comparable, although TURP has consistently displayed a slight advantage over needle ablation for most variables analyzed, except quality of life score. The advantages of needle ablation over TURP are (1) performance in the office as an outpatient procedure, (2) no need for general or spinal anesthesia, (3) rapid recovery, (4) minimal side effects, and (5) one-time intervention. The following disadvantages exist with needle ablation: (1) it may not be indicated or effective in patients with large prostate glands (75 g or more); (2) no prostate tissue is available for histologic evaluation; and (3) no long-term efficacy or re-treatment rate data have been published. Overall, the available information indicates that transurethral needle ablation is a viable minimally invasive treatment that may be applicable in men with moderate to severe bladder outlet obstruction as a result of an enlarged prostate gland.

Alpha-blockade therapy for benign prostatic hyperplasia: from a nonselective to a more selective alpha1A-adrenergic antagonist.

Benign prostatic hyperplasia (BPH) is very common in older men, causing symptoms that can markedly impair quality of life. Surgical treatment, typically transurethral resection of the prostate (TURP), is highly effective but can be costly and is associated with the risk for significant morbidity. Medical treatments for BPH are targeted toward reducing bladder outlet obstruction either by androgen blockade to reduce prostatic volume or alpha-adrenergic blockade to relax the smooth muscle tone of the prostate. In recent years, understanding of the sympathetic innervation of the prostate has improved. This has been paralleled by the development of alpha-adrenergic blocking agents, from nonselective alpha-antagonists, to selective alpha1-antagonists, to the more selective alpha1A-antagonists. It is anticipated that more specific agents will optimize the therapeutic effectiveness of alpha-adrenergic blockade in the prostate while reducing the side effects associated with alpha-adrenergic blockade in other areas of the body, such as the vascular system. This article reviews the evolution of alpha-blockade therapy in management of BPH, focusing on tamsulosin, an agent targeted toward the alpha1A-adrenoceptor that predominates in the prostate. Clinical trials in Europe and the United States have provided evidence that tamsulosin is effective at doses of 0.4 and 0.8 mg/day. At both doses, tamsulosin is associated with significant improvements in the American Urological Association symptom score and the mean and peak urinary flow rates as compared with placebo. This once-daily alpha1A-adrenergic antagonist is well-tolerated, with a minimal potential for the side effects associated with alphas-blocker therapy.

Serum percent-free PSA does not predict extraprostatic spread of prostate cancer.

Percent-free prostate-specific antigen (proportion of free prostate-specific antigen [PSA] to total PSA) has been shown recently in studies on frozen serum samples to be more useful than total PSA alone in distinguishing prostate cancer from benign conditions of the prostate gland. The primary purpose of our study was to determine whether percent-free PSA could predict extraprostatic spread of prostate cancer. We also sought to evaluate the freeze-thaw stability of free PSA. Percent-free PSA values in fresh serum samples were compared with those in aliquots subjected to one to five freeze-thaw cycles. Percent-free PSA values in frozen serum samples from 130 men undergoing radical prostatectomy for clinically localized prostate cancer were compared across pathologic stages. Free PSA levels remained stable for up to five freeze-thaws. Great overlap was found in percent-free PSA values for men with organ-confined disease and those with extraprostatic spread. These results indicate that multiple freeze-thaw cycles do not significantly affect free PSA levels and percent-free PSA is not useful in identifying ideal candidates for radical prostatectomy.

Biologic variability of prostate-specific antigen and its usefulness as a marker for prostate cancer: effects of finasteride. Finasteride PSA Study Group.

OBJECTIVES: The effects of finasteride on prostate-specific antigen (PSA) variability and usefulness in prostate cancer detection were examined. METHODS: Percent change and crossover of PSA levels between the low (1.0 to 3.9 ng/mL) and high (4.0 to 10.0 ng/mL) ranges were evaluated in 72 men with benign prostatic hyperplasia (BPH) and 77 men with both BPH and prostate cancer (PCa) treated with finasteride or placebo for 6 months. Patients with PCa were studied as a model for evaluating the effects on PSA levels in patients with BPH and latent PCa. As recommended on the product label, PSA levels for finasteride-treated patients were doubled for interpretation. RESULTS: In patients with BPH, most placebo- and finasteride-treated patients with low PSA levels at baseline had subsequent PSA levels below 4.0 ng/mL throughout the study. Among patients with high baseline PSA levels, only 1 of 17 finasteride-treated patients, compared with 8 of 13 placebo-treated patients, crossed into the low range. In the BPH/PCa study, most placebo-treated patients maintained PSA levels in the same range (15 of 19 less than 4.0 ng/mL; 14 of 16 greater than 4.0 ng/mL). Almost one third of finasteride-treated patients with low PSA levels at baseline crossed into the high range (8 of 22), whereas most patients with high PSA levels at baseline were not masked with treatment, with PSA levels remaining high (12 of 15). CONCLUSIONS: PSA levels cross between the low and high PSA ranges in both finasteride- and placebo-treated patients with BPH and those with both BPH and PCa. Doubling the PSA levels in finasteride-treated patients allows appropriate interpretation of PSA values and does not mask the detection of PCa.

A prospective, randomized 1-year clinical trial comparing transurethral needle ablation to transurethral resection of the prostate for the treatment of symptomatic benign prostatic hyperplasia.

PURPOSE: We assess the 1-year efficacy and safety of transurethral needle ablation of the prostate compared to transurethral resection of the prostate for the treatment of symptomatic benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A prospective, randomized clinical trial of 121 men 50 years old or older with symptomatic BPH was performed at 7 medical centers across the United States. Of the men 65 (54%) were treated with transurethral needle ablation of the prostate and 56 (46%) underwent transurethral resection of the prostate. Mean and percentage changes from baseline and between cohorts for American Urological Association (AUA) symptom score, AUA bother score, quality of life score, peak urinary flow rate and post-void residual urine volume were measured at 1, 3, 6 and 12 months following treatment. Length of procedure, hospitalization, type of anesthesia, post-procedure catheterization, side effects and sexual function were compared. RESULTS: Transurethral needle ablation and resection resulted in a statistically significant improvement in AUA symptom, bother and quality of life scores, peak urinary flow rate and post-void residual. At 1-year followup, needle ablation and resection were equally effective in enhancing quality of life. Needle ablation had less effect on sexual function, with resection being associated with a greater incidence of retrograde ejaculation. Needle ablation could be performed as an outpatient procedure with local anesthesia while resection required anesthesia and hospitalization. Needle ablation was associated with markedly fewer side effects than resection. CONCLUSIONS: Compared to transurethral resection of the prostate, transurethral needle ablation of the prostate is an efficacious, minimally invasive treatment for symptomatic BPH that is associated with few side effects.

Transurethral needle ablation for benign prostatic hyperplasia: 12-month results of a prospective, multicenter U.S. study.

OBJECTIVES: To report the safety and efficacy of the transurethral needle ablation (TUNA) procedure for the treatment of clinical benign prostatic hyperplasia (BPH). METHODS: One hundred thirty patients with BPH were enrolled in two identical protocols and treated by the TUNA procedure. Entry criteria included an American Urological Association symptom index (AUA SI) of 13 points or higher and a peak flow rate of 12 mL/s or less. Patients were followed up for 12 months. Efficacy parameters included the AUA SI, AUA problem index, BPH impact index (BPH II), quality of life (QOL) score, and peak flow rate. At each visit, side effects were elicited. Follow-up data are available for 93 patients at 12 months. All patients were given intraurethral lidocaine augmented by oral and/or parenteral sedation. No patient received spinal or general anesthesia. RESULTS: All patients tolerated the procedure well, and there were no deaths. Forty-one percent of patients (n = 53) had a catheter placed immediately after the procedure. At 12 months, the AUA SI had decreased from 23.7 to 11.9 (P < 0.0001) and the BPH II from 7.5 to 2.5 (P < 0.0001), whereas the peak flow rate had increased from 8.7 to 14.6 mL/s (P < 0.0001). Irritative voiding symptoms were noted in 20 patients (16%) at some point during follow-up. Two patients reported erectile dysfunction, and 1 reported retrograde ejaculation. CONCLUSIONS: In this prospective study of 130 patients with clinical BPH and lower urinary tract symptoms, TUNA provided substantive and lasting improvement according to AUA SI, BPH II, and QOL scores as well as peak flow rate over 1 year. The TUNA procedure was well tolerated, with few major side effects and complications noted. Longer follow-up is needed to document the maintenance of clinical benefit beyond 12 months.

Benign prostatic hyperplasia: use of drug therapy in primary care.

Age and normal male androgenic function are the two most well-established risk factors for benign prostatic hyperplasia. Clinical manifestations of BPH may range from minimally bothersome symptoms to urinary retention and renal failure. Digital rectal examination, serum PSA, urinalysis, serum creatinine, and the AUA symptom score are recommended for the initial evaluation. For mild symptoms, watchful waiting may be all that is needed. For severe symptoms, surgical therapy is the most appropriate option. For men with mild to moderate symptoms, less invasive procedures and several pharmacologic therapies have proved to be effective for treating BPH. The pharmacologic therapies include a 5 alpha-reductase inhibitor (finasteride) and three selective alpha-1 blockers (terazosin, doxasozin, and tamsulosin).

A model for the number of cores per prostate biopsy based on patient age and prostate gland volume.

PURPOSE: The systematic sextant biopsy is currently the gold standard for the tissue diagnosis of prostate cancer. However, it is unknown whether this 6 core approach provides optimal sampling of all prostate glands in men of all ages. The goal of the current study was to determine the appropriate number of cores per prostate biopsy based on patient age and prostate gland volume. MATERIALS AND METHODS: Patient age and tumor volume doubling time were used to calculate life threatening, clinically significant tumor volumes at diagnosis for 5-year intervals of patient age. A mathematical model was created to determine the minimum number of cores necessary to identify these life threatening tumor volumes in prostate glands 10 to 80 cm.3 without detecting clinically insignificant cancers. RESULTS: Younger men and men with larger prostate glands require more than 6 cores to ensure the diagnosis of life threatening prostate cancer. These prostates are currently under sampled by sextant biopsy. In a select group of older men who require fewer than 6 cores sextant biopsy may over sample these prostates and lead to over treatment. CONCLUSIONS: The standard sextant biopsy provides optimal sampling of only a minority of prostate glands. An approach to prostate biopsy based on patient age and prostate gland volume maximizes the detection of clinically significant prostate cancer.

Serial prostate-specific antigen measurements in men with clinically benign prostatic hyperplasia during a 12-month placebo-controlled study with terazosin. HYCAT Investigator Group. Hytrin Community Assessment Trial.

OBJECTIVES: To prospectively analyze whether the treatment of men with clinically benign prostatic hyperplasia (BPH) with alpha blocking agents affects the serum prostate-specific antigen (PSA) levels, and to determine the magnitude of such effect. METHODS: Serial PSA measurements were performed using the Abbott IMx assay over 1 year in 134 men over the age of 55 years participating in the Hytrin Community Assessment Trial (HYCAT). HYCAT is a 1-year, randomized, placebo-controlled, double-blinded study of the alpha1-adrenergic antagonist terazosin. All men had lower urinary tract symptoms and a clinical diagnosis of BPH with an American Urological Association (AUA) symptom index of 13 points or more, an AUA bother score of 8 points or more, and a peak urinary flow rate of less than 15 mL/s. PSA was measured at baseline and at 8, 26, 39, and 52 (end of study) weeks. RESULTS: Baseline serum PSA levels weakly correlated with patients' age at study entry, and modestly with residual urine (positive correlation) and peak flow rate (negative correlation), although none of the levels were statistically significant. Changes of serum PSA during the course of the study did not correlate with either one of the symptom severity or bother assessment tools, residual urine, or peak flow rate. Mean PSA increased from a baseline of 2.5+/-0.22 ng/mL (mean+/-SE) by 0.5+/-0.11 ng/mL in the placebo-, and from 2.7+/-0.23 ng/mL by 0.3+/-0.11 ng/mL in the terazosin-treated patients (P = 0.36 by ANOVA). There were no differences in the changes in serum PSA when patients were stratified by decade of life according to the age-specific PSA reference ranges, or by the final dose of terazosin (2, 5, or 10 mg daily). CONCLUSIONS: The treatment of men with lower urinary tract symptoms and clinical BPH with the alpha1-adrenergic antagonist terazosin does not affect serum PSA concentration, and thus does not confound longitudinal monitoring of serum PSA levels in patients at risk for prostate carcinoma.

Update on the appropriate staging evaluation for newly diagnosed prostate cancer.

PURPOSE: Prostate cancer clinical staging methods and decision support tools were reviewed to assess their accuracy to predict pathological staging results and determine what comprises an appropriate clinical staging evaluation. MATERIALS AND METHODS: The MEDLINE data base was searched and 238 abstracts were obtained. Data were extracted from 142 articles that evaluated the preoperative accuracy of digital rectal examination, prostate specific antigen, prostatic acid phosphatase, systematic biopsy parameters (including Gleason scoring), seminal vesicle biopsy, various imaging studies and pelvic lymphadenectomy versus pathological staging results. The sensitivity, specificity and accuracy rates were calculated and tabulated from the reported data on each method or decision support tools for organ confined, nonorgan confined and lymph node metastatic tumor. RESULTS: Decision support tools based on logistic regression analysis, which combine several statistically independent staging parameters, had greater accuracy than any single clinical staging method alone. The most accurate decision support tools for clinical staging combined digital rectal examination (T stage), systematic biopsy parameters (including Gleason scoring) and prostate specific antigen. CONCLUSIONS: The components that comprise the most accurate decision support tools for clinical staging represent an appropriate staging evaluation for the newly diagnosed prostate cancer patient in 1997. Limited use of radiographic imaging and seminal vesicle biopsy may be indicated in select patients to detect bone metastases, and plan pelvic lymphadenectomy and surgical therapy.

A nationwide survey of practicing urologists: current management of benign prostatic hyperplasia and clinically localized prostate cancer.

PURPOSE: Our aim was to define the spectrum of urological care for benign prostatic hyperplasia (BPH) and clinically localized prostate cancer. MATERIALS AND METHODS: In 1995 a random sample of 394 American urologists was surveyed with a response rate of 67%. RESULTS: Respondents reported seeing a median of 240 BPH patients during the preceding 12 months, and they had prescribed alpha-blockers for 70 and finasteride for 15. They had performed a median of 25 transurethral prostatectomies but few other operations for BPH. Almost all urologists routinely used digital rectal examinations and prostate specific antigen tests for BPH diagnosis. The next most common studies were American Urological Association symptom scores and uroflowmetry. Pressure-flow studies were rarely done. Respondents reported seeing a median of 35 new patients with prostate cancer during the last year, and performing a median of 90 prostate biopsies and 13 radical prostatectomies. Respondents had referred a median of 10 patients for external beam radiotherapy but few patients received brachytherapy or cryotherapy. Urologist staging practices varied considerably. CONCLUSIONS: These data provide a picture of current practice regarding the management of BPH and prostate cancer.

The relationship between prostatic intraepithelial neoplasia and prostate cancer: critical issues.

PURPOSE: Prostatic intraepithelial neoplasia (PIN) is often considered to be a premalignant lesion and the main precursor of invasive carcinoma of the prostate. We evaluated the evidence for and against PIN as a premalignant lesion and determined guidelines for the clinical management of PIN. MATERIALS AND METHODS: Literature analysis of histopathological, morphometric, phenotypic and molecular genetic evidence of progression and of clinical findings regarding PIN was done. Literature searches were performed on MEDLINE with relevant key words. RESULTS: PIN, like prostate cancer, occurs most frequently in the peripheral zone of the prostate and is usually located in close proximity to prostate cancer. The relative PIN and prostate cancer volumes vary inversely. Prostate specific antigen in cases of PIN appears to be intermediate between prostate cancer and normal levels, although this elevation may be explained by concomitant prostate cancer or benign prostatic hyperplasia. Deoxyribonucleic acid ploidy in PIN follows the aneuploid proportion as in the concomitant prostate cancer. Prostate cancer and PIN show evidence of loss of putative tumor suppressor genes on chromosome 8p. The clinical relevance of PIN biopsy findings is based on the association of neoplasia and prostate cancer. High grade PIN in core biopsies without concomitant prostate cancer has a substantial risk for prostate cancer in subsequent biopsies (24 to 73%, up to 100% when the digital rectal examination is suspicious) and should cause further biopsy sampling. CONCLUSIONS: There is convincing evidence that PIN is a precursor lesion to prostate cancer, with a close association of PIN and prostate cancer in biopsy and prostatectomy specimens. A biopsy finding of high grade PIN necessitates further investigation in patients who are candidates for radical treatment for localized prostate cancer.