Clinical Evidence Of Prostate Cancer Research Articles

Outcome of TRUS Biopsy with Limited Cores in Patients with PSA More Than 50ng/dL: Can We Reduce the Number of Cores Without Affecting Outcomes?

The aims of our study were to see outcomes of limited core biopsy and compare its outcomes with standard 12-core biopsy in patients with PSA more than 50ng/dL. We did a retrospective analysis of 149 patients undergoing prostatic biopsy with PSA more than 50ng/dL between January 2014 and December 2018. Out of 149 patients, 49 underwent limited core (2 to 6 cores) TRUS biopsy with no systemic 12-core biopsy. Other 100 patients underwent standard 12-core biopsy under TRUS guidance. Total of 149 patient's records were analyzed and were included in the final analysis. There was no significant difference in demographics and prostate-specific antigen among the cohorts. All 49 patients in limited core TRUS biopsy had a positive biopsy with no need of re-biopsy. Fourteen out of 100 patients in TRUS biopsy had a negative biopsy. All 14 patients with negative biopsy had an average follow-up of 3.8years with no conversion to positive biopsy. Patients with PSA more than 50ng/dL and high clinical suspicion of prostate cancer can undergo limited core biopsy without systemic 12-core biopsy. In patients with no clinical evidence of prostate cancer, 12-core biopsy remains the gold standard for evaluation of prostate cancer.

Age-specific Serum Prostate Specific Antigen Ranges Among Apparently Healthy Nigerian Men Without Clinical Evidence of Prostate Cancer.

Introduction:Serum prostate specific antigen (PSA) levels increase with age and varies among different races and communities. The study was aimed at defining the age-specific reference ranges of serum PSA in our environment.Methods:We evaluated the relationship between age and serum PSA levels and the age-specific reference ranges of serum PSA among civil servants in Lagos, who underwent routine medical checkups. Criteria for inclusion were men who have no lower urinary tract symptoms, normal digital rectal examination and serum PSA ≤ 20 ng/ml. SPSS Statistic 21 was used for data evaluation and the mean, median, 95th percentile PSA levels were estimated. Pearson's correlation was used to examine the relationship, and P < 0.05 was considered significant.Results:4032 men met the criteria for inclusion in the evaluation. The mean age was 51.6 (range 40–70) years, and there was a strong correlation between serum PSA levels and age (r = 0.097, P < 0.001). PSA ranges of 0–2.5, >2.5–4.0, >4.0–10, and >10 ng/ml were found in 3218 (80%), 481 (12%), 284 (7%), and 52 (1%) men, respectively. The mean, median and the 95th percentile PSA for the overall group were 1.84, 1.33, and 5.2 ng/ml respectively. However the 95th percentile PSA levels for men aged 40–49, 50–59, and 60–70 years were 4.78, 5.47, and 8.93 ng/ml respectively.Conclusion:The age-specific PSA levels among Nigerian men for each age group is higher than what was described for men in the Western world. These reference ranges of serum PSA should be considered for men aged ≥40 years in our environment.

Cardiovascular Risk Factors and Ethnicity Are Independent Factors Associated with Lower Urinary Tract Symptoms.

ObjectivesTo determine the lower urinary tract symptoms (LUTS) profile and factors affecting its degree of severity including cardiovascular risk profile, age, ethnicity, education level and prostate volume in a multiethnic Asian setting.Materials and MethodsWe conducted a cross-sectional study of 1021 men aged 40–79 years with no clinical evidence of prostate cancer, prostate surgery or 5α-reductase inhibitor treatment of known prostate conditions. The severity of LUTS was assessed using the International Prostate Symptom Score (IPSS). Potential factors associated with LUTS including age, ethnicity, education, history of hypertension, diabetes and hypercholesterolemia, height, weight, and prostate volume were evaluated using univariable and multivariable analyses.ResultsThere were 506 (50%) men found to have moderate-to-severe LUTS attaining an IPSS above 7. Overall, nocturia (45.5%) was the most frequently reported symptom. Multivariable analysis showed that age, ethnicity, prostate volume and history of hypertension and hypercholesterolemia were independent factors associated with severity of LUTS (p < 0.05). Considering individual lower urinary tract symptoms, we found a strong association of storage symptom with history of hypertension and hypercholesterolemia. Malay men were significantly bothered by post micturition symptom compared to their Chinese and Indian counterparts. Stratified analyses of LUTS demonstrated a mutually exclusive cardiovascular risk factors profile defined by ethnicity.ConclusionSeverity of LUTS varies between different ethnicities across all age groups. In addition to age and prostate volume, ethnicity and cardiovascular risk factors including hypertension and hypercholesterolemia may also need to be taken into account in managing men with LUTS.

Earlier prostate-specific antigen testing in African American men—Clinical support for the recommendation

BackgroundTo determine whether prostate-specific antigen (PSA) testing in African American veterans (AAVs) aged 40 to 54 years is associated with high-risk prostate cancer characteristics compared with AAVs aged 55 to 70 years or white veterans (WVs) aged 40 to 54 years. MethodsA total of 231,174 healthy veterans aged 40 to 70 years without clinical evidence of prostate cancer underwent PSA testing between October 1, 2000, and September 30, 2007. Clinicopathologic tumor characteristics were available for 1,044/1,059 AAVs and 1,006/1,971 age-matched WVs diagnosed with prostate cancer after a PSA level>4ng/ml triggered prostate biopsy. Tumor characteristics of AAVs aged 40 to 54 years were compared with AAVs 55 to 70 years, WVs 40 to 54 years, and WVs 55 to 70 years. ResultsOf PSA-tested veterans aged 40 to 54 years diagnosed with prostate cancer, there were no racial differences in prebiopsy PSA levels, prostate cancer grade, or clinical stage at diagnosis. AAVs aged 40 to 54 years were more likely to have≥3 positive cores (P = 0.0229) and were less likely to be active surveillance candidates (P = 0.0340) compared with similarly aged WVs. AAVs aged 55 to 70 years were more likely to have high-grade (P = 0.0204) and higher clinical stage (P = 0.0195) prostate cancer than AAVs aged 40 to 54 years. ConclusionsThis large national cohort study suggests that PSA testing at an earlier age for African American men may allow diagnosis of lower risk prostate cancer, potentially reducing disparate outcomes between AAVs and WVs.

Ethnicity is an independent determinant of age-specific PSA level: findings from a multiethnic Asian setting.

ObjectivesTo study the baseline PSA profile and determine the factors influencing the PSA levels within a multiethnic Asian setting.Materials and MethodsWe conducted a cross-sectional study of 1054 men with no clinical evidence of prostate cancer, prostate surgery or 5α-reductase inhibitor treatment of known prostate conditions. The serum PSA concentration of each subject was assayed. Potential factors associated with PSA level including age, ethnicity, height, weight, family history of prostate cancer, lower urinary tract voiding symptoms (LUTS), prostate volume and digital rectal examination (DRE) were evaluated using univariable and multivariable analysis.ResultsThere were 38 men (3.6%) found to have a PSA level above 4 ng/ml and 1016 (96.4%) with a healthy PSA (≤4 ng/ml). The median PSA level of Malay, Chinese and Indian men was 1.00 ng/ml, 1.16 ng/ml and 0.83 ng/ml, respectively. Indians had a relatively lower median PSA level and prostate volume than Malays and Chinese, who shared a comparable median PSA value across all 10-years age groups. The PSA density was fairly similar amongst all ethnicities. Further analysis showed that ethnicity, weight and prostate volume were independent factors associated with age specific PSA level in the multivariable analysis (p<0.05).ConclusionThese findings support the concept that the baseline PSA level varies between different ethnicities across all age groups. In addition to age and prostate volume, ethnicity may also need to be taken into account when investigating serum PSA concentrations in the multiethnic Asian population.

Influence of Opioid Consumption on Serum Prostate-specific Antigen Levels in Men Without Clinical Evidence of Prostate Cancer

To determine the effect of opioid consumption on the serum prostate-specific antigen (PSA) level. From April 2009 to December 2011, 56 opioid users and 82 age-matched controls participated in the present study. The exclusion criteria were prostate cancer or other malignancies, serum PSA level ≥ 4 ng/dL, abnormal digital rectal examination findings, previous prostate surgery, pelvic radiotherapy, bladder stone, urinary tract infection, recent prostatic manipulation, and a history of taking drugs that alter the serum PSA level. The prostate volume and PSA, serum testosterone, and luteinizing and follicle-stimulating hormone levels were measured in the eligible participants and compared between the opioid users and control subjects. The study was conducted in accordance with the Declaration of Helsinki, and the institutional review board approved the study. The serum PSA level was significantly lower in opioid users compared with that in the control subjects (0.82 ± 0.77 vs 1.95 ± 1.00, P < .001). The testosterone level was also lower in the opioid users (339.08 ± 142.49 vs 396.71 ± 133.64, P = .008). The difference between the PSA levels remained significant when a comparison was performed between the eugonadal opioid users and eugonadal control subjects. Moreover, the effect of opioid consumption on the PSA level persisted on multivariate analysis, controlling for serum testosterone level. Opium consumption was associated with significant decline in the serum PSA level and warrants adjustment in the PSA cutpoints at which biopsy is recommended. Opioid-induced hypogonadism does not seem to account for the PSA decline, and additional studies are required to determine the involved mechanisms.

Screening for prostate cancer using multivariate mixed-effects models

Using several variables known to be related to prostate cancer, a multivariate classification method is developed to predict the onset of clinical prostate cancer. A multivariate mixed-effects model is used to describe longitudinal changes in prostate-specific antigen (PSA), a free testosterone index (FTI), and body mass index (BMI) before any clinical evidence of prostate cancer. The patterns of change in these three variables are allowed to vary depending on whether the subject develops prostate cancer or not and the severity of the prostate cancer at diagnosis. An application of Bayes’ theorem provides posterior probabilities that we use to predict whether an individual will develop prostate cancer and, if so, whether it is a high-risk or a low-risk cancer. The classification rule is applied sequentially one multivariate observation at a time until the subject is classified as a cancer case or until the last observation has been used. We perform the analyses using each of the three variables individually, combined together in pairs, and all three variables together in one analysis. We compare the classification results among the various analyses and a simulation study demonstrates how the sensitivity of prediction changes with respect to the number and type of variables used in the prediction process.

Lower Urinary Tract Symptoms Affect One-Third of Men in a Prostate Cancer Screening Population

Lower urinary tract symptoms (LUTS) are common in elderly men. Radical prostatectomy may relieve obstructive symptoms, whereas radiation therapy may exacerbate obstructive or irritative symptoms. Baseline LUTS rates are unknown in populations screened for prostate cancer (PCa). Thus, it is difficult to determine the changes in LUTS that can be attributed to PCa treatment. Therefore, we assessed baseline rates of LUTS in a PCa screening cohort and assessed which of the International Prostate Symptom Score (IPSS) symptoms had the most detrimental effect on quality of life (QoL). The IPSS was completed by 1273 men without clinical evidence of PCa who participated in an annual PCa screening event. Presence of irritative or obstructive symptoms was considered when they were reported at least two of five times. Using linear regression analyses, we evaluated the effect of each questionnaire symptom on the IPSS QoL domain. Mean age was 57.6 years (range 40-89 years). Of all in the cohort, 40% (n = 472) reported moderate to severe LUTS (IPSS score > or =8), and 21% (n = 255) were mostly dissatisfied with this condition. Irritative symptoms were reported by 39% (n = 495) and obstructive symptoms by 37%. Of all IPSS symptoms, urinary straining was associated with the least favorable QoL, followed by urinary frequency. More than one-third of persons at risk of PCa are affected by either irritative or obstructive symptoms, and one in five of these men is bothered by LUTS. Because PCa treatment may exacerbate LUTS, the severity and impact on QoL should be considered carefully before diagnosis and/or treatment.

Distribution of prostate specific antigen (PSA) and percentage free PSA in a contemporary screening cohort with no evidence of prostate cancer: Chun FK, Hutterer GC, Perrotte P, Gallina A, Valiquette L, Benard F, McCormack M, Briganti A, Ionescu C, Jeldres C, Guay JP, Saad F, Karakiewicz PI, Department of Urology, University Medical Centre Eppendorf, Hamburg, Germany

Objective To explore the distribution of total prostate specific antigen (PSA) and percentage free/total PSA (%f/tPSA) in healthy volunteers with no clinical evidence of prostate cancer, who participated in prostate cancer screening. Subjects and Methods PSA and %f/tPSA values from 2,323 men, who participated in one of three annual prostate cancer screening events between 2004 and 2006, were tabulated according to age strata of 40–49, 50–59, 60–69, and 70–79 years. Local regression smoothing plots provided a graphical display of the relation between age and PSA or %f/tPSA, respectively. All PSA and %f/tPSA analyses were repeated for each age category after excluding, respectively, the top and the bottom 10% of PSA and %f/tPSA values. Results Within the entire cohort, the median PSA level was 1.0 ng/ml and the median %f/tPSA was 25%. According to the age categories the PSA level and %f/tPSA medians within the entire cohort were, respectively, 0.7, 0.9, 1.3, 1.8 ng/ml and 28.0, 26.0%, 24.0%, and 25.0%. Of the 2,323 men, 438 (18.9%) had a PSA level of >2.5 ng/ml and 1,172 (50.5%) had a %f/tPSA of ≤25%. When either a PSA level of >2.5 ng/ml or a %f/tPSA of ≤25% were considered, 1,235 (53.2%) had one or two abnormal values. Finally, if either a PSA level of >2.5 ng/ml or %f/tPSA of ≤15% was used, 617 (26.6%) were considered abnormal. Conclusion Half of the men with no clinical evidence of prostate cancer should have PSA levels of 25%. A PSA level threshold of 2.5 ng/ml would require a biopsy in 20% of men and a %f/tPSA threshold of ≤ 25% in half of the men. Alternatively, a %f/tPSA threshold of ≤15% would decrease the probability to 15%.

Ejaculatory Disorders May Affect Screening for Prostate Cancer

Ejaculatory disorders will be experienced in most men who are treated for localized prostate cancer. Baseline rates of ejaculatory disorders are unknown in men at risk for prostate cancer. Therefore, we explored the prevalence of those disorders and associated bother in men without evidence of prostate cancer who participated in an annual prostate cancer screening event. A cohort of 1,273 men without clinical evidence of prostate cancer completed the self-administered Danish Prostate Symptom Score for sexual dysfunction. This questionnaire quantifies the rate of reduced ejaculatory volume, ejaculatory pain and the rate of coexistent erectile dysfunction. Mean age was 57.6 years (range 40 to 89). Of all men 46% (563) had reduced ejaculatory volume and 66% (356) of affected men were bothered by this condition. Ejaculatory pain was reported in 11% (134) and 89% (118) of these men reported associated bother. Finally, 45% (554) reported erectile dysfunction and 73% (403) reported associated bother. Reduced ejaculatory volume was associated with erectile dysfunction (p<0.001) and advanced age (p<0.001). Ejaculatory pain was not associated with one of these variables. Virtually all men will be affected by ejaculatory disorders after definitive treatment for localized prostate cancer. Therefore, it is important to observe that half of these individuals already have underlying reduced ejaculatory volume before treatment. Moreover, 1 of 10 men will be affected by ejaculatory pain. Both disorders are a significant source of bother and should be considered when treatment related quality of life is assessed.

Distribution of prostate specific antigen (PSA) and percentage free PSA in a contemporary screening cohort with no evidence of prostate cancer

To explore the distribution of total prostate specific antigen (PSA) and percentage free/total PSA (%f/tPSA) in healthy volunteers with no clinical evidence of prostate cancer, who participated in prostate cancer screening. PSA and %f/tPSA values from 2323 men, who participated in one of three annual prostate cancer screening events between 2004 and 2006, were tabulated according to age strata of 40-49, 50-59, 60-69 and 70-79 years. Local regression smoothing plots provided a graphical display of the relation between age and PSA or %f/tPSA, respectively. All PSA and %f/tPSA analyses were repeated for each age category after excluding, respectively, the top and the bottom 10% of PSA and %f/tPSA values. Within the entire cohort, the median PSA level was 1.0 ng/mL and the median %f/tPSA was 25%. According to the age categories the PSA level and %f/tPSA medians within the entire cohort were, respectively, 0.7, 0.9, 1.3, 1.8 ng/mL and 28.0, 26.0, 24.0 and 25.0%. Of the 2323 men, 438 (18.9%) had a PSA level of >2.5 ng/mL and 1172 (50.5%) had a %f/tPSA of < or = 25%. When either a PSA level of >2.5 ng/mL or a %f/tPSA of < or = 25% were considered, 1235 (53.2%) had one or two abnormal values. Finally, if either a PSA level of >2.5 ng/mL or %f/tPSA of < or = 15% was used, 617 (26.6%) were considered abnormal. Half of men with no clinical evidence of prostate cancer should have PSA levels of <1.0 ng/mL and a %f/tPSA of >25%. A PSA level threshold of 2.5 ng/mL would require a biopsy in 20% of men and a %f/tPSA threshold of < or = 25% in half of the men. Alternatively, a %f/tPSA threshold of < or = 15% would decrease the probability to 15%.

Comparison of calcaneal bone density in operative versus non-operative army personnel

Purpose: To study the response of nonmalignant prostatic tissue to ionizing irradiation in terms of the resultant changes in serum prostate specific antigen (PSA) levels.Methods and Materials: Weekly serum PSA values were determined during radiotherapy (RT)_in nine patients (“treatment group”) without clinical evidence of prostate cancer (PC), and who received pelvic RT for other indications. Slopes fr the rate of change in PSA was determined using model: log PSA = β0 + β1∗week + β2∗week2 + error. These results are compared with 17 normal volunteers (“control group”) who were not exposed to ionizing irradiation. an attempt is made to compare any similarities and differences in subsets of 64 T1–T4NOMO PC patients who received pelvic RT.Results: An elevation in the serum PSA levels were noted in eight of nine patients in the “treatment group” with a median time of 4.2 weeks to reach the maximum serum PSA values. After an initial increase, PSA values declined. In some patients, manifold increase in PSA was noted, for exampel, from 1.8 to 13.5 ng/ml and 3.3 to 9.8 ng/ml in two patients. The PSA increase ranged from 50–650%. The median slope was 0.601 week−1 (range 0.192–3.045 week−1). No such increases were seen in the “control group” (median slope = 0.03 week−1; range, 0.18–0.13 week−1). When diffrences between the mean increase/decrease for each week compared to pretreatment values were analyzed, the irradiated group had statistically significant elevations in the PSA for weeks 3 (p = 0.034), 4 (p = 0.24). A similar ternd of increasing PSA levels during radiotherapy was noted in prostate cancer patients whose initial PSA values were ≤ 20 ng/ml: whereas positive slopes (i.e., increasing PSA levels during radiotherapy course) was seen in 7.1% of those with > 20 ng/ml preradiotherapy PSA values, such trends were seen in52.7% of those with ≤ 20 ng/ml preradiotherapy PSA values.Conclusion: (a) Incidental exposure of noncancerous prostate to ionizing irradiation appears to lead to an initial elevation followed by a decline in serum PSA. (b) Similar elevations in serum (PSA) levels are seen in over 50% of prostate cancer patients with ≤ 20 ng/ml pretreatment PSA. (c) Acinal cell death and sudden release of PSA into the circulation is the most likely explanation for our observations, although other mechanism cannot be excluded. (d) Our observations have to be considered in modeling PSA kinetics induced by RT and in correlating such kinetics to long-term outcomes. (e0 Our findings in the control group indicate that there appears to be no significant variation in serum PSA over many weeks under physiological conditions in normal healthy ambulatory men.

Prostate specific-antigen distribution in asymptomatic Canadian men with no clinical evidence of prostate cancer

To examine prostate specific-antigen (PSA) levels and percentage free/total PSA (f/tPSA) distributions as well as digital rectal examination (DRE) profiles in asymptomatic Canadian men with no established prostate cancer diagnosis, as recent data indicate that a man's risk of developing prostate cancer is higher if his baseline PSA level is above the median for his age group. We used data obtained during an early prostate cancer-detection event. An invitation to an onsite DRE, PSA level and f/tPSA assessment was accepted by 313 men. Serum PSA level and f/tPSA were measured before the DRE. A suspicious DRE and/or PSA level of > or = 2.5 ng/mL or f/tPSA of < or = 15% represented indications for a systematic 12-core ultrasonography-guided prostate biopsy. Of all the 313 men, most (235, 75%) had PSA levels of 0.01-1.53 ng/mL and an f/tPSA of >15% (285, 91.1%). The median (range) PSA level was 0.8 (0-34.2) ng/mL and f/tPSA was 27.4 (6.7-100)%. Age-specific median PSA levels and f/tPSA were, respectively, 0.7, 0.9, 1.0, 1.5 ng/mL and 31%, 27%, 26%, 25% for men aged 40-49, 50-59, 60-69 and 70-79 years. A suspicious DRE was recorded in 55 (17.6%) men, with eight (8.8%), 26 (20.0%), 14 (20.6%), and seven (28.9%) having suspicious DRE findings according to above age categories. Overall, seven (2.2%) prostate cancers were detected. The median age-specific baseline PSA levels and f/tPSA represent valuable indicators of prostate cancer risk. The population-specific baseline median PSA level should not be >1.0 ng/mL and the baseline f/tPSA should be >30%. Men with values outside of these ranges should be considered at greater risk of prostate cancer.

Effects of Chronic Bacterial Prostatitis on Prostate Specific Antigen Levels Total and Free in Patients with Benign Prostatic Hyperplasia and Prostate Cancer

Prostatic-specific antigen (PSA), a tumor marker helpful in the diagnosis and follow-up of prostate cancer, may rise due to causes such as prostatitis, chronic benign prostatic hyperplasia (BHP), etc. The aim of this study was to investigate the relationship between prostatitis and the level of total and free prostate-specific antigen in patients with no clinical evidence of prostate cancer. A comprehensive urological examination was performed on 156 patients aged 35-61 years old. All patients have symptoms of prostatitis. Prostate fluid culture was preformed. All patients underwent a course of antibacterial treatment after which the levels of total prostate specific antigen (TPSA) and free prostate specific antigen (FPSA) were evaluated. An increase in TPSA (> 4 ng/ml) was observed in 14/24 (58.3%) patients with acute prostatitis and in 7/45 (15.5%) and 4/44 (9.1%) in patients with chronic bacterial prostatitis (CBP) and a bacterial prostatitis, respectively. Low blood concentration of TPSA and FPSA were observed after effective antibacterial and anti-inflammatory treatment therapy in most cases. These data suggested that prostatitis must be considered when interpretation of TPSA and FPSA values as tumor marker.

Population Standards of Prostate Specific Antigen Values in Men over 40: Community Based Study in Turkey

To determine the prostate specific antigen (PSA) population standards of a cluster of Turkish men with no clinical evidence of prostate cancer. We evaluated PSA values of the men who were living in a well-defined, rural district of Western Anatolia. Two hundred fifty-seven men agreed to participate in this population-based study. They underwent clinical examination, transrectal ultrasonography and serum PSA measurement. The association between serum PSA and age, prostate volume and age, PSA and prostate volume, and PSA density (PSAD) and age were assessed. Distributions of serum PSA levels, prostate volumes (PV), and PSAD values as a function of age were generated. The upper limit of normal PSA concentration were 4.51 ng/ml for men aged 40-49 years, 4.36 ng/ml for 50-59 years, 6.17 ng/ml for 60-69 years, and 10.18 ng/ml for over 70 years. The upper limit of normal (95th percentile) for the serum PSA concentration increased with age. Across the entire age range, no correlation was found between the serum PSA concentrations and age while significant correlation was found between serum PSA concentration and prostate volume. In this present study, the PSA values in different age intervals showed higher than those observed in previous studies. The PSA values are mainly affected by prostate volume rather than age.

Sustained Decrease in Incidence of Acute Urinary Retention and Surgery With Finasteride for 6 Years in Men With Benign Prostatic Hyperplasia

We determined the effect of long-term treatment with finasteride on the incidence of acute urinary retention (AUR) and benign prostatic hyperplasia (BPH) related surgery in men with BPH. The Proscar (Merck and Co., Inc., Whitehouse Station, New Jersey) Long-Term Efficacy and Safety Study (PLESS) was comprised of 3040 men with enlarged prostates, moderate to severe symptomatic BPH and no clinical evidence of prostate cancer. Patients were randomized to placebo or 5 mg finasteride daily for 4 years. Of the 3016 randomized patients with available efficacy data 62% completed the original 4-year study (1006 on finasteride and 891 on placebo) and 89% of these (908 from the original finasteride arm and 785 from the placebo arm) continued in a 2-year open extension on finasteride. Followup was attempted in discontinued patients. Complete 6-year outcomes data, including 6-year followup in 770 men who had discontinued treatment during years 1 to 6, were available for 2463 (82%) of the 3016 originally randomized patients. For patients on continuous finasteride treatment the decrease in incidence of AUR and/or BPH related surgery in the 4-year base study was sustained during the open extension. In patients who were switched from placebo to finasteride in the extension, the incidence of AUR and/or BPH related surgery was similar to that in the continuous finasteride arm. The 6-year data from PLESS confirmed and further extended the findings from the original 4-year trial, demonstrating that finasteride treatment led to a sustained decrease in the incidence of AUR and/or BPH related surgery in men with BPH and enlarged prostates.

The Long-Term Clinical Impact of Biochemical Recurrence of Prostate Cancer 5 or More Years After Radical Prostatectomy

Information regarding the clinical impact of delayed (5 years or greater) biochemical failure (BF) after radical prostatectomy (RP) is lacking. We undertook an investigation to differentiate the innocuous recurrence of serum prostate specific antigen (PSA) from that which heralds an eventual clinical failure (CF), and to determine if there is a period following RP when a patient is cured of clinical disease. Men with clinically localized prostate cancer (PCA) undergoing RP (1987 to 1995) were identified from our longitudinal PCA registry. Outcome measurements were based on the detection of post-RP serum PSA 0.4 ng/ml or greater, clinical identification of cancer recurrence and disease related death. Following RP in 3,903 eligible men, 33% had a detectable PSA (median followup 8.8 years). Of these BFs 27% occurred after 5 or more disease-free years. Currently, 29% of all men with BF have clinical evidence of PCA, with 8% dying of PCA (median actuarial survival time from CF to death 9.8 years). Progression from BF to CF was not significantly altered by the disease-free interval (p = 0.544). A PSA doubling time less than 12 months significantly increased the risk of CF regardless of the interval from surgery. Risk factors for BF were significant throughout the duration of followup. Patients are at prolonged risk for BF and CF following RP. Regardless of the timing of the initial PSA recurrence the PSA doubling time is the most powerful predictor of progression, stratifying patients with BF into high and low risk groups for CF.

Relationship of serum sex-steroid hormones and prostate volume in African American men.

Previous epidemiologic investigations of the associations of sex-steroid hormones and benign prostatic hyperplasia (BPH) have focused on predominately white populations. The objective of this study was to evaluate potential associations of body mass index (BMI), cigarette smoking, use of alcohol, and endogenous sex-steroid hormones with prostate volume in a population-based sample of African American (AA) men, ages 40-79 yr. A total of 369 AA men without clinical evidence of prostate cancer were identified in the Flint Men's Health Study by using a population-based sampling procedure. All subjects underwent a complete urologic evaluation that included prostate volume determination by transrectal ultrasonography and serum assays for androgens and estrogens. After age adjustment, BMI (weight (kg)/height (m)2) was positively correlated with increasing levels of androstanediol glucuronide (AG), estradiol (E2), estrone sulfate (E1S), and the ratios of E2:total testosterone (TT) and E2:free testosterone (FT); however, increasing BMI was negatively correlated with androstenedione (AD), FT, TT, and sex hormone-binding globulin (SHBG). Multivariable regression models demonstrated that prostate volume increased with age (P < 0.001) and BMI (P = 0.02) and decreased with increasing levels of SHBG (P = 0.01). Larger prostatic volumes were also marginally associated with increasing levels of TT (P = 0.058). Circulating serum levels of SHBG and endogenous sex-steroid hormones are correlated with prostate volume and potentially impact the natural history of BPH. However, longitudinal studies are needed to demonstrate the temporal relationships of hormones and growth factors in the pathogenesis of BPH in AA men.

Detection of telomerase activity in prostatic fluid specimens

We report here the extended use of the telomeric repeat amplification protocol (TRAP) assay for the detection of telomerase activity in fresh prostatic fluid obtained from anesthetized patients. Telomerase activity was detected in pellet extract and/or supernatant fluid of specimens obtained from 25 of 30 prostate cancer (PCa) patients (83%), whereas no activity was similarly detectable in specimens taken from 8 of 9 patients (89%) without clinical evidence of PCa. The positive predictive value (PPV) of the TRAP assay for PCa in this pilot study was 96%. We found a strong correlation between telomerase activity in prostatic fluid specimens and serum prostate specific antigen (PSA) values. Telomerase activity was found in 84% of specimens from patients with PSA values >4 ng/ml, whereas in specimens from patients with PSA values ⩽4 ng/ml, only 29% tested positive for telomerase activity. In patients with PSA values above the standard 0 to 4 ng/ml reference range, the PPV of the TRAP assay was 84%. Furthermore, telomerase activity could be detected in 85% of the specimens from PCa patients with Gleason scores >4. In prostatic fluid from PCa patients with Gleason scores of ⩽4, telomerase activity was detected 50% of the time. The PPV was 92% when a Gleason score of 4 was used as the lower limit. This pilot study raises the possibility of utilizing telomerase activity as an aid in PCa detection.

Serum prostate-specific antigen levels (PSA) in men without clinical evidence of prostate cancer: age-specific reference ranges for total PSA, free PSA, and percent free PSA

Objectives. To investigate the relationship between age and total prostate-specific antigen (tPSA), free PSA (fPSA), and percent free PSA (%fPSA) in men 48 to 79 years old without clinical evidence of prostate cancer. We determined age-specific ranges for each parameter and compared the results with previously published studies in similar populations. Methods. Nine hundred eighty-three men (96% white) from the random-sample community-based Massachusetts Male Aging Study were analyzed. Men with PSA 4.1 ng/mL or greater were referred for biopsy and those with positive biopsies or with medical record, cancer registry, or self-reported evidence of prostate cancer were excluded. Results. The median tPSA increased 38.6% per decade (95% confidence interval 28.7% to 49.3%). Because of the greater variability at older ages, the 95th percentile increased faster than the median, leading to the following age-specific upper limits of normal: 2.84 for 50 to 59 years, 5.87 for 60 to 69 years, and 9.03 for 70 to 79 years. The pattern of association between fPSA and age was similar to tPSA. The 50th and 5th percentiles of %fPSA were 25.3% and 13.2%, respectively, regardless of age. Conclusions. Establishing age-specific screening cutoffs based on the age-specific upper limits of normal will ensure low false-positive biopsy rates but may also lead to low true positive rates (ie, low sensitivity) in older age groups. Both sensitivity and specificity should be considered when counseling patients. The independence of %fPSA with age confirms others’ findings.