Age-specific Prostate-specific Antigen Reference Research Articles

Ethnic differences in the age-related distribution of serum prostate-specific antigen values: A study in a Taiwanese male population.

This study investigates age-specific prostate-specific antigen (PSA) distributions in Taiwanese men and recommends reference ranges for this population after comparison with other studies. From January 1999 to December 2016, a total of 213,986 Taiwanese men aged above 19 years old without history of prostate cancer, urinary tract infection, or prostate infection were recruited from the Taiwan MJ cohort, an ongoing prospective cohort of health examinations conducted by the MJ Health Screening Center in Taiwan. Participants were divided into seven age groups. Simple descriptive statistical analyses were carried out and quartiles and 95th percentiles were calculated for each group as reference ranges for serum PSA in screening for prostate cancer in Taiwanese men. Serum PSA concentration correlated with age (r = 0.274, p<0.001). The median serum PSA concentration (5th to 95th percentile) ranged from 0.7 ng/ml (0.3 to 1.8) for men 20-29 years old (n = 6,382) to 1.6 ng/ml (0.4 to 8.4) for men over 79 years old (n = 504). The age-specific PSA reference ranges are as follows: 20-29 years, 1.80 ng/ml; 30-39 years, 1.80 ng/ml; 40-49 years, 2.0 ng/ml; 50-59 years, 3.20 ng/ml; 60-69 years, 5.60 ng/ml; 70-79 years, 7.40 ng/ml; over 80 years, 8.40 ng/ml. Almost no change occurred in the median serum PSA value in men 50 years old or younger, while a gradual increase was observed in men over 50. Taiwanese men aged 60 years above showed higher 95th percentile serum PSA values compared to Caucasian men and men in other Asian countries but were closer to those of Asian American and African American men. Results indicate significantly different PSA levels correlating to different ethnicities, suggesting that Oesterling's age-specific PSA reference ranges might not be appropriate for Taiwanese men. Our results should be further studied to validate the age-specific PSA reference ranges for Taiwanese men presented in this study.

Prostate-specific antigen age-specific reference ranges and the effect of metabolic syndrome factors in a Thai population Authors

Objectives: An appropriate prostate specific antigen (PSA) cut-off value in Thailand has not been investigated, nor has an age-specific PSA reference range. This study aims to evaluate the correlation between metabolic syndrome, metabolic factors, and age specific PSA level. Materials and Methods: A cross-sectional study in men who underwent medical checkups from September 2019 to December 2019. The 95th percentile PSA value was applied to the normal age-specific reference range. Correlations between PSA levels and a variety of factors were determined using linear regression. Results: A total of 507 men met the criteria to be included in the analysis. Age-specific PSA reference ranges for men aged 40-49, 50-59, and 60-70 years were 0-2.3, 0-3.4, and 0-4.2 ng/ml, respectively. The multivariate adjusted geometric mean PSA model indicated that the factors related to PSA were age, higher body mass index (BMI) and serum fasting blood sugar (FBS) ≥ 100 mg/dl. The age group 50-59 and 60-70 have a 43% and 99% increase in mean PSA compared to the age group 40-49, respectively (p &lt; 0.001). A higher BMI was associated with lower PSA (p &lt; 0.001). And the serum FBS ≥ 100 mg/dl showed a 15% reduction in mean PSA compared to FBS &lt; 100 mg/dl (p = 0.018). Conclusion: The age-specific PSA reference in Thai men was lower than reported in a previous study. Use of the lower PSA cut-off may increase the sensitivity of prostate cancer screening. This study demonstrates that age, BMI, and FBS may all influence the clinical interpretation of serum PSA levels. Screening for prostate cancer using PSA should be carried out with caution in those who have those risk factors.

Prostate-specific Antigen Screening Using the Traditional Cut Point of 3 ng/ml: Con

The prostate-specific antigen (PSA) threshold of 3.0 ng/ml is obsolete because it yields a test that is too sensitive. Urologists should adopt a more nuanced approach that accounts for benign prostate hypertrophy. This includes the use of magnetic resonance imaging, PSA density, and age-specific PSA reference ranges.

Decreasing trend in prostate cancer with high serum prostate-specific antigen levels detected at first prostate-specific antigen-based population screening in Japan.

To clarify the recent trends in prostate-specific antigen (PSA) distribution in men in Japan, we analyzed the PSA distributions of men undergoing PSA-based population screening. We summarized the annual individual data of PSA-based population screening in Kanazawa, Japan, from 2000 to 2011, and analyzed baseline serum PSA values of the participants at the first population screening. Serum PSA distributions were estimated in all participants and those excluding prostate cancer patients according to age. From 2000 to 2011, 19 620 men participated aged 54–69 years old in this screening program. Mean baseline serum PSA level of all participants at the first screening was 2.64 ng ml−1 in 2000, and gradually decreased to approximately 1.30 ng ml−1 in 2006. That of participants excluding prostate cancer patients was 1.46 ng ml−1 in 2000, and there was no remarkable change during the study period. The 95th percentiles in the participants excluding prostate cancer patients detected at the first population screening of men aged 54–59, 60–64, and 65–69 years old were 2.90, 3.60, and 4.50 ng ml−1, respectively. After the commencement of population screening, the proportion of prostate cancer patients with high serum PSA levels decreased. However, there were no changes in serum PSA levels in men without prostate cancer. Age-specific PSA reference level of men without prostate cancer in Japan was similar to that in China and Korea.

Critical Appraisal of Prostate-specific Antigen in Prostate Cancer Screening: 20 Years Later

Prostate-specific antigen (PSA) is secreted by all types of prostate epithelial cells and has been used for 2 decades as a biologic marker for prostate cancer (PCa). Since the implementation of PSA screening in the United States, the detection of PCa has increased, accompanied by a decrease in the incidence of high-grade cancer and PCa-specific mortality rates. It has been suggested that these decreases have resulted from the enhanced detection of PCa while still curable. These data have been the impetus for early detection programs, which have recommended the initiation of screening as early as 40 years of age. Despite widespread use, PSA screening remains controversial, principally because of the lack of evidence from randomized controlled trials demonstrating a mortality benefit that could outweigh the concerns of the costs of overdiagnosis and overtreatment. Two ongoing, randomized controlled trials are examining whether screening reduces the risk of PCa-related mortality, and the results of these studies are expected soon. Although it has its limitations, PSA still remains the best-studied marker for the detection of PCa.

Age-specific PSA reference ranges in Chinese men without prostate cancer

This study is to determine age-specific prostate-specific antigen (PSA) distributions in Chinese men without prostate cancer (PC) and to recommend reference ranges for this population after comparison with other studies. From September 2003 to December 2006, 9 374 adult men aged from 18 to 96 years agreed to participate in the study. After all cases of PC were excluded, 8 422 adult men participated in statistical analysis and were divided into five age groups. Simple descriptive statistical analyses were carried out and quartiles and 95th percentiles were calculated for each age group. The age-specific PSA reference ranges are as follows: 40-49 years, 2.15 ng mL(-1); 50-59 years, 3.20 ng mL(-1); 60-69 years, 4.10 ng mL(-1); 70-79 years, 5.37 ng mL(-1). The results indicate that the ethnic differences in PSA levels are obvious. The currently adopted Oesterling's age-specific PSA reference ranges are not appropriate for Chinese men. The reference ranges of this study should be more suitable to Chinese men.

Age-Specific Prostate-Specific Antigen Reference Ranges in Korean Men

The serum prostate-specific antigen (PSA) level varies widely among different races and increases with age. In this study, we evaluated the variation in serum PSA levels in a multicenter study population to determine a standard age-specific PSA reference range for Korean men without clinically evident prostate cancer. We retrospectively analyzed 120,439 Korean men, ranging in age from 30 to 79 years, whose serum PSA levels were measured at one of eight referral hospitals from November 1998 to July 2005. Our recommended age-specific reference ranges (95th percentile) of serum PSA levels for Korean men were 0.32 to 1.88 ng/mL for men 30 to 39 years, 0.30 to 1.92 ng/mL for men 40 to 49 years, 0.30 to 2.37 ng/mL for men 50 to 59 years, 0.31 to 3.56 ng/mL for men 60 to 69 years, and 0.30 to 5.19 ng/mL for men 70 to 79 years old. The serum PSA level increased annually, corresponding to an increase of 0.0023 ng/mL for men in their 40s, 0.0175 ng/mL for men in their 50s, 0.0499 ng/mL for men in their 60s, and 0.0398 ng/mL for men in their 70s, with a steep increase for men in their 50s and the largest increase in men older than 60 years. The results of our study have shown that the age-specific reference ranges (95th percentile) for serum PSA levels in Korean men are lower than those for white men. Our newly proposed age-specific reference ranges from this multicenter study will be more valuable in the interpretation of PSA data for Korean men.

Pathologic Characteristics of Prostate Cancers Missed by Application of the Age-specific Prostate-specific Antigen Reference in Men over Sixties

To examine the pathologic characteristics of prostate cancers missed by application of the age-specific prostate-specific antigen(PSA) reference in Korean men over sixties in clinical practice based on PSA cutoff 3.0ng/ml. Materials and Methods: We made retrospective analysis of 1,063 patients aged between 60-79 who had had transrectal ultrasonography(TRUS)- guided biopsy due to the rise of PSA over 3.0ng/ml or abnormal findings in digital rectal examination(DRE) or TRUS. Age-specific PSA reference was set at 3.9ng/ml for 60s and 5.4ng/ml for 70s. Results: Prostate cancer was detected in 34.3%(365/1,063) as a whole, and 31.5% in 60s, and 39.5% in 70s according to the age. When age-specific reference 3.9ng/ml was applied to 60s, 20(9.6%) cancers were missed compared with clinical cutoff value(3.0ng/ml). When age-specific reference 5.4ng/ml was applied to 70s, 23(16.0%) cancers were missed. On the average, 43(12.2%) of cancers were missed in 60s and 70s. Of 43 missed cancers, 39(90.7%) were with normal DRE and TRUS. Of these cancers, 16(41.0%) were clinically insignificant on biopsy, but only 7(22.6%) were insignificant in the pathologic examination of 31 radical prostatectomy specimens. Conclusions: In our clinical practice based on PSA cutoff 3.0ng/ml, most cancers missed by application of age-specific reference are clinically significant. But, considering the positive effect of age-specific reference on avoidance of unnecessary biopsies, large prospective study is needed to evaluate the efficacy of age-specific reference in Korean men over sixties.

Detection rates and biologic significance of prostate cancer with PSA less than 4.0 ng/mL: Observation and clinical implications from Tyrol screening project

Objectives To investigate the prostate cancer (PCa) detection rates and Gleason scores in patients with serum prostate-specific antigen (PSA) levels of 2.0 to 3.9 ng/mL and 4.0 to 10 ng/mL (free PSA 18% or less), in a population-based screening project. With the use of prostate-specific antigen (PSA) screening, more PCa is being diagnosed at PSA values of less than 4 ng/mL. Methods A total of 3446 consecutive screening volunteers with a PSA level of 2.0 to 10.0 ng/mL (free PSA 18% or less) were assessed. Ten systematic prostate biopsies and an additional five Doppler-enhanced targeted biopsies were performed on the basis of age-specific PSA reference ranges. The cumulative frequency of detection and the Gleason scores were analyzed. Results The PCa detection rate for patients with a PSA value of 2.0 to 3.9 ng/mL (n = 1522, group 1) and 4.0 to 10.0 ng/mL (n = 1924, group 2) was 21% (n = 320) and 30% (n = 572), respectively. Of the PCa cases detected, 37% were in men with a PSA level of 2 to 4 ng/mL. Statistically significant differences were found in age and prostate volume between groups 1 and 2, with patients in the lower PSA group younger and having a smaller mean prostate volume ( P = 0.0001). Of 313 patients with PCa and a PSA value of 2 to 3.9 ng/mL, 24% had a Gleason score of 7 or greater compared with 33% of 560 patients with a PSA value of 4.0 to 10.0 ng/mL ( P = 0.004). Conclusions Our data suggest that in a screening population, more than one third of PCa cases in men with a PSA level of 2 to 10 ng/mL will occur in those with a PSA value of 2 to 3.9 ng/mL. Also, PCa cases with a low PSA level occur in younger patients and at lower stages with a smaller prostate volume.

The Clinical Usefulness of Prostate-Specific Antigen (PSA) Level and Age-Specific PSA Reference Ranges for Detecting Prostate Cancer in Chinese

Introduction: To determine the role of prostate-specific antigen (PSA) level and age-specific PSA reference ranges for detecting prostate cancer in Chinese. Material and Methods: We retrospectively reviewed the medical records of all 50- to 79-year-old men who had their first-time prostatic biopsy done at our institute between January 1998 and December 2000. We evaluated the effect on biopsy rate and cancer detection if the PSA cutoff was shifted from 4.0 ng/ml to the age-specific reference ranges. Also, we tried to develop age-adjusted PSA cutoffs for Chinese. Results: Among 1,236 men enrolled, 252 (20.4%) were diagnosed as prostate cancers. The positive predictive value was 22.2% for PSA >4.0 ng/ml. Using the traditional age-specific PSA reference ranges 134 (10.8%) biopsies could be avoided but five (1.98%) cancers would be missed. We proposed age-specific PSA reference ranges for Chinese as: 0–4.0 ng/ml for men in their 50s and 0–6.0 ng/ml for men between 60 and 79 years. Had we used these alternative cutoffs, 150 (12.1%) biopsies could be saved, of them 3 were cancers. Conclusions: The age-specific PSA reference ranges may help to avoid 12% of biopsies but 1.2% of prostate cancers would have gone undetected. Among population with low incidence of prostate cancer as Chinese, minimizing unnecessary biopsies might be more important issue than maximizing cancer detection rate.

Age-specific distribution of serum prostate-specific antigen in a community-based study of African-American men

Objectives. Previous studies have observed higher age-specific serum prostate-specific antigen (PSA) values in African-American (AA) men without prostate cancer compared to white men, leading some to recommend race-specific PSA reference ranges for the early detection of prostate cancer. The primary objective of the Flint Men’s Health Study was to determine age-specific PSA reference values in a community-based sample of AA men, aged 40 to 79 years. Methods. A probability sample of 943 AA men was selected from households in Genesee County, Michigan. Men without a prior history of prostate cancer/surgery were invited to participate in a prostate cancer screening protocol, consisting of measurement of serum total PSA, free/total PSA ratio, and digital rectal examination. Sextant biopsies were recommended, based on total PSA greater than 4.0 ng/mL and/or an abnormal digital rectal examination. Results. From the sample of 943 men, 732 were eligible, 432 had blood drawn for PSA testing, and 374 completed all phases of the clinical examination. The 95th percentile PSA values were estimated to range from 2.36 ng/mL for men in the fifth decade to 5.59 ng/mL for men in the eighth decade. The 95th percentile values for age-specific PSA were comparable to those observed in a similar study of white men in Olmsted County, Minnesota. The median and 5th percentile values for free/total PSA did not vary significantly across age. Conclusions. The minor differences in PSA reference ranges between AA and white men may not be of sufficient magnitude to recommend the use of race-specific PSA reference ranges for screening.

Usefulness of age-specific reference range of prostate-specific antigen for japanese men older than 60 years in mass screening for prostate cancer

Objectives. To investigate the age-specific reference range of prostate-specific antigen (PSA) in Japanese men older than 60 years of age by analyzing the receiver operating characteristic (ROC) curve. Several reports have noted that many clinically serious cancers are missed by raising the cutoff value of the age-specific PSA reference range for men older than 60 years. Methods. We studied 6744 individuals who had undergone mass screening for prostate cancer in Gunma Prefecture from 1994 to 1998. PSA determination was the first step of the mass screening in all subjects. Digital rectal examination and transrectal ultrasonography (TRUS) were performed in all except in a fraction of patients. Subjects with an abnormal PSA level or abnormal digital rectal examination or TRUS findings underwent TRUS-guided systematic sextant biopsies. Patients older than 60 years of age were grouped according to their age at 5-year intervals, and the cutoff value of the age-specific PSA reference range was calculated for each age group by analyzing the ROC curve. Results. The diagnostic efficiency of the age-specific PSA reference range was optimal with cutoff values of 3.0, 3.5, 4.0, 4.0, and 7.0 ng/mL in subjects 60 to 64, 65 to 69, 70 to 74, 75 to 79, and older than 80 years of age, respectively. By using the age-specific PSA reference range as determined by the ROC curve, the sensitivity, specificity, and efficiency increased to 92.4%, 91.2%, and 84.3%, respectively. When the standard PSA reference range was used for the diagnosis, the sensitivity, specificity, and efficiency was 89.1%, 92.4%, and 82.3%, respectively. All of the cases of prostate cancer detected by using the age-specific PSA reference range with the cutoff point based on the ROC curves were clinically significant. Conclusions. The age-specific PSA reference range cutoff value in this setting demonstrated better diagnostic efficiency than the standard cutoff value of PSA and the age-specific PSA reference range determined by the 95% confidence interval. It appears likely to be a useful diagnostic index for the first step of mass screening in Japanese men.

Comparison of percent free PSA, PSA density, and age-specific PSA cutoffs for prostate cancer detection and staging

Objectives. Various methods have been proposed to increase the specificity of prostate-specific antigen (PSA), including age-specific PSA reference ranges, PSA density (PSAD), and percent free PSA (%fPSA). In this multicenter study, we compared these methods for their utility in cancer detection and their ability to predict pathologic stage after radical prostatectomy in patients with clinically localized, Stage T1c cancer. Methods. Seven hundred seventy-three men (379 with prostate cancer, 394 with benign prostatic disease), 50 to 75 years old, from seven medical centers were enrolled in this prospective blinded study. All subjects had a palpably benign prostate, PSA 4.0 to 10.0 ng/mL, and a histologically confirmed diagnosis. Hybritech’s Tandem PSA and free PSA assays were used. Results. %fPSA and age-specific PSA cutoffs enhanced PSA specificity for cancer detection, but %fPSA maintained significantly higher sensitivities. Age-specific PSA cutoffs missed 20% to 60% of cancers in men older than 60 years of age. %fPSA and PSAD performed equally well for detection (95% sensitivity) if cutoffs of 25% fPSA or 0.078 PSAD were used. The commonly used PSAD cutoff of 0.15 detected only 59% of cancers. %fPSA and PSAD also produced similar results for prediction of the post-radical prostatectomy pathologic stage. Patients with cancer with higher %fPSA values (greater than 15%) or lower PSAD values (0.15 or less) tended to have less aggressive disease. Conclusions. The results of this study demonstrated that cancer detection (sensitivity) is significantly higher with %fPSA than with age-specific PSA reference ranges. %fPSA and PSAD provide comparable results, suggesting that %fPSA may be used in place of PSAD for biopsy decisions and in algorithms for prediction of less aggressive tumors since the determination of %fPSA does not require ultrasound.

Value of Free Prostate-Specific Antigen (Hybritech Tandem-R) in Symptomatic Patients Consulting the Urologist

Introduction: Prostate-specific antigen (PSA) is a widely used tumor marker in the detection and follow-up of adenocarcinoma of the prostate. Selection of candidates for prostate biopsies is hampered by the lack of specificity resulting in a large number of unnecessary biopsies. The intention of our study was to compare the percent free PSA (f-PSA; Hybritech Tandem-R) with total PSA and age-specific PSA reference values to evaluate the clinical benefit in detecting patients with prostate cancer (PC) in a selected group of patients consulting the urologist. The question was whether cutoff points are influenced by this selection of patients. Methods: A total of 188 patients, 114 with benign prostate hyperplasia (BPH) and 74 with PC were selected. It is a selected group of patients consulting the urologist. Diagnosis was confirmed in the BPH and PC groups by either ultrasound-guided biopsy or transurethral resection of the prostate or suprapubic adenomectomy or cystoprostatectomy. Total PSA (t-PSA) and f-PSA of all patients were measured before any manipulation by Tandem-R assay for f-PSA and Tandem-E assay for t-PSA (Hybritech). Mean values of age, prostate volume, t-PSA, f-PSA, percent f-PSA were compared in patients with BPH and PC by Mann-Whitney U test. The sensitivity and specificity of t-PSA and age-specific PSA were compared to the sensitivities and specificities of different cutoff points of percent f-PSA. Results: The mean value of t-PSA, f-PSA and percent f-PSA in patients with BPH (n = 114) and PC (n = 74) were statistically significantly different. At PSA levels between 4 and 10 ng/ml 19% of negative biopsies could be avoided by the use of percent f-PSA (cutoff point 25%). There was no additional benefit of age-specific PSA. At a PSA of <4 ng/ml 6 of 7 PCs could be diagnosed by percent f-PSA (cutoff point 25%), whereas only 1 patient would be diagnosed by age-specific PSA. Conclusion: Percent f-PSA seems to decrease the biopsy rate at PSA levels from 4 to 10 ng/ml without missing a relevant number of cancers and to increase the detection rate at PSA <4 ng/ml. Our data indicate that it might be necessary to choose high cutoff points (25%; Tandem-E and R assay, Hybritech) in a selected study population consulting the urologist with large glands and a high prevalence of disease. However, this situation is not comparable to testing of screening populations. No benefit of age-specific PSA could be observed in this study.

The role of prostate specific antigen measurement in the detection and management of prostate cancer.

The introduction of prostate specific antigen (PSA) testing has revolutionised the early detection, management and follow-up of patients with prostate cancer and it is considered to be one of the best biomedical markers currently available in the field of oncology. Its use with annual digital rectal examination in prostate cancer screening programmes has led to a marked change in the distribution of stage at presentation towards earlier disease and led to a significant increase in the detection of potentially curable disease. In order to improve the specificity of PSA testing and thereby reduce the number of unnecessary prostatic biopsies, a number of refinements of PSA evaluation have been proposed. These include free to total PSA ratio, PSA density, PSA density, PSA density of the transition zone, PSA velocity and age-specific PSA reference ranges. The utility of these approaches is considered in this review. The role of PSA monitoring in the detection of recurrence following radical prostatectomy and radiotherapy is discussed, as well as its role in monitoring patients treated with endocrine therapy is discussed, as well as its role in monitoring patients treated with endocrine therapy in terms of correlating PSA response with outcome, in detecting disease progression and in guiding the use of subsequent therapies. Large continuing multicentre screening and outcome studies will provide important information enabling greater refinement of the use of this important diagnostic and monitoring tool in the future detection and management of prostate cancer.

SHOULD THE AGE SPECIFIC PROSTATE SPECIFIC ANTIGEN CUTOFF FOR PROSTATE BIOPSY BE HIGHER FOR BLACK THAN FOR WHITE MEN OLDER THAN 50 YEARS?

Investigators who have examined age specific reference ranges recommend a higher prostate specific antigen (PSA) cutoff for biopsy for black than for white men older than 50 years. We controlled for PSA to determine whether age specific reference range cutoffs for diagnosis defined by the Walter Reed Army Medical Center group (Walter Reed group) would improve the disproportionate prostate cancer prognosis between black and white men. We studied 651 consecutive patients who underwent radical prostatectomy at Wayne State University between 1991 and 1995 with a mean followup of 34 months (range 1.5 to 75). Log rank tests were used to determine the homogeneity of survival functions between black and white men with similar PSA ranges, and between groups defined by age specific PSA reference ranges for each race. Disease stage and grade were similar or worse in black men for any PSA range, and biochemical disease-free survival was similar or worse within each range. Black men had a higher percentage of high grade prostate cancer than white men 60 to 69 years old who would not have undergone biopsy using the Walter Reed group proposed PSA cutoff. Black men have similar or worse prostate cancer severity and outcome than white men with similar PSA ranges. Using age specific reference ranges for the PSA test defined by the Walter Reed group, black men have worse outcome than white men after radical prostatectomy. Therefore, we recommend that the PSA cutoff for biopsy should not be higher for black men at any age range.

Most prostate cancers missed by raising the upper limit of normal prostate-specific antigen for men in their sixties are clinically significant

Objectives. To evaluate the efficacy of applying an age-specific prostate-specific antigen (PSA) reference range to determine whether prostate biopsies are warranted in men 60 to 69 years of age. We estimated the incidence of clinically significant prostate cancer in men in their sixties with PSA levels of 4.01 to 4.50 ng/mL and normal digital rectal examinations (DRE). Methods. We reviewed 203 sextant prostate biopsies of men in their sixties with PSA levels of 4.01 to 4.50 ng/mL and normal DRE. Tumors were considered clinically significant if the cancer on biopsy was poorly differentiated (Gleason score of 7 or more), involved more than one core, or included a single focus measuring more than 3 mm. Results. The positive biopsy rate was 31.5%. More than 80% of the cancers detected satisfied criteria that almost always predict clinically significant cancer. Thus, among men in their sixties with PSA levels of 4.01 to 4.50 ng/mL and normal DRE, the risk of detecting clinically significant cancer on biopsy was approximately 25%. Conclusions. Most nonpalpable cancers detected by sextant biopsies in men 60 to 69 years of age with PSA levels of 4.01 to 4.5 ng/mL are clinically significant. Applying an age-specific PSA reference range that increases the upper limit of normal PSA to 4.5 ng/mL results in the failure to detect a substantial number of clinically significant cancers.

AGE SPECIFIC PROSTATE SPECIFIC ANTIGEN REFERENCE RANGES: POPULATION SPECIFIC

Purpose We determined whether 60 to 79-year-old men with a negative digital rectal examination and a serum prostate specific antigen (PSA) within age specific PSA reference ranges could safely forgo prostate biopsy. Materials and Methods We reviewed the medical records of all 60 to 79-year-old men at the Brooklyn Veterans Administration Medical Center who had a PSA assay, digital rectal examination and subsequent prostate biopsy for an abnormal rectal examination and/or PSA greater than 4.0 ng./ml. from January 1991 through August 1995. We compared our results using the standard reference range of 0 to 4.0 ng./ml. with those obtained had we used any of 4 different age specific PSA reference ranges. Results We performed 1,280 prostate biopsies in 1,046 men with available PSA and digital rectal examination data. Using age specific PSA reference ranges 73 of 1,280 biopsies (5.7%) would have been avoided. Of those 73 avoided biopsies 15 (20.5%) had cancer that would have gone undetected and 9 of 15 (60%) undetected cancers had unfavorable histology. Results were not statistically significantly different among the 4 age specific PSA reference ranges. Regarding race, cancer detection rates were significantly higher for black compared with white men but there was no statistically significant difference for missed cancers or missed cancers with unfavorable histology. Conclusions In contrast to previous reports of unfavorable histological characteristics in only 5% of missed cancers using age specific PSA reference ranges, 60% of missed cancers in our patients exhibited unfavorable histology. We conclude that age specific PSA reference ranges did not safely eliminate the need for prostate biopsy in our study population. In 60 to 79-year-old men with a negative digital rectal examination we continue to use PSA greater than 4.0 ng./ml. as an indication for prostate biopsy.

Prostate cancer, Incidence, management and outcomes.

The incidence of prostate carcinoma in the US now appears to be declining slightly, as a consequence of removal of prevalent cases from the population by screening. Screening for serum prostate-specific antigen (PSA) levels has been improved by the use of PSA transformations including PSA density, PSA velocity and age-specific PSA reference ranges. The ratio of free to total PSA may increase the specificity of single serum PSA evaluations without decreasing its sensitivity for the diagnosis of prostate cancer. Despite the proliferation of risk assessment tools and nomograms, the optimal therapy for localised disease remains controversial, and the usefulness of radical prostatectomy or radiation therapy (either external beam or brachytherapy) has not been tested prospectively against watchful waiting. However, watchful waiting is probably more appropriate for men whose life expectancy is less than 10 to 15 years and/or who have low grade tumours. In patients with metastatic disease, androgen deprivation remains the mainstay of treatment. Whether or not the addition of an antiandrogen prolongs survival remains controversial. Intermittent androgen deprivation appears to be one means of avoiding continuous androgen deprivation and possibly decreasing adverse effects, although its efficacy remains to be proven. For patients whose disease progresses after combined androgen blockade, withdrawal of antiandrogen is now considered mandatory. Tremendous heterogeneity exists among patients who progress after antiandrogen withdrawal, so that patients previously considered resistant to hormones may in fact retain some hormonal sensitivity to second- or third-line hormone therapy. For patients with hormone-refractory prostate cancer, a variety of options exist, including the use of estramustine combinations, suramin, mitoxantrone and doxorubicin combinations. Despite these options, there is presently no standard of care, and clinical trials should receive priority. Palliative interventions, including the use of corticosteroids, radiopharmaceuticals and external beam radiation therapy, should not be overlooked.

Serial prostate-specific antigen measurements in men with clinically benign prostatic hyperplasia during a 12-month placebo-controlled study with terazosin

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 alpha 1-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 alpha 1-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.