Prostate-specific antigen as an estimator of prostate volume in the management of patients with symptomatic benign prostatic hyperplasia

OBJECTIVES: To assess the ability of serum prostate specific antigen (PSA) to estimate prostate volume (PV) to aid in the management of patients with benign prostatic hyperplasia (BPH). METHODS: From 1989 to 2002, data were collected from 2264 patients complaining of lower urinary tract symptoms (LUTS) who visited the Department of Urology of the University Medical Centre Nijmegen, The Netherlands. Baseline PV and serum PSA was determined using standard techniques. All patients who had a baseline PV < or =200 ml, as well as a baseline serum PSA 0-10 ng/ml, were included. Patients with a history of prostate surgery, prostate cancer and conditions other than BPH at baseline were excluded. A log-transformed linear regression model was used to estimate PV. Receiver-operating characteristic (ROC) curves were constructed to evaluate the ability of serum PSA to estimate threshold PVs in men with BPH, and to select the optimal serum PSA cut-off values. RESULTS: The analyses included 1859 patients with a mean age of 63.5 years, mean baseline PV 43.9 ml, and mean baseline PSA value 3.1 ng/ml. PV as well as serum PSA increases with age. Linear regression analyses showed that PV and serum PSA have an age-dependent log-linear relationship, where 42% of the variance of PV can be explained by PSA and age. ROC's area under the curves (AUC) reveal that PSA has a good predictive value for assessing 'prostate enlargement', with AUC around 82% in the overall age groups irrespective of the PV cut-off values. Optimal serum PSA cut-off values for the overall study population irrespective of age are 2.0 ng/ml to detect PV >30 ml and 2.5 ng/ml to detect PV >40 ml. CONCLUSIONS: This study suggests that serum PSA can estimate prostate enlargement sufficiently accurately to be useful for therapeutic, especially medical, management. It is well accepted that the outcome of pharmacotherapy for BPH depends on baseline PV. Therefore, in the absence of reliable direct measurement of PV, serum PSA determination may be used to optimise patient management.     

Clinical outcomes after combined therapy with dutasteride plus tamsulosin or either monotherapy in men with benign prostatic hyperplasia (BPH) by baseline characteristics: 4-year results from the randomized, double-blind Combination of Avodart and Tamsulosin (CombAT) trial

What’s known on the subject? and What does the study add? Treatment of benign prostatic hyperplasia (BPH) centres on two drug classes, 5α‐reductase inhibitors and α‐blockers. The 4‐year Combination of Avodart® and Tamsulosin (CombAT) study investigated whether the combination of dutasteride and tamsulosin was more effective than either monotherapy in reducing the relative risk of AUR, BPH‐related surgery, and BPH clinical progression in men with moderate‐to‐severe LUTS who were at increased risk of disease progression. Data from the 2‐ and 4‐year, pre‐planned primary and secondary endpoint analyses for the CombAT study have been reported previously. This study reports the outcomes of post hoc analyses of the influence of baseline parameters on the incidence of AUR, BPH‐related surgery, and overall clinical progression in patients treated with tamsulosin, dutasteride, or combination therapy with both agents.

OBJECTIVE

? To investigate the influence of baseline variables on the 4‐year incidence of acute urinary retention (AUR), benign prostatic hyperplasia (BPH)‐related surgery and overall clinical progression in men treated with tamsulosin, dutasteride, or a combination of both.

PATIENTS AND METHODS

? The 4‐year Combination of Avodart® and Tamsulosin (CombAT) study was a multicenter, randomized, double‐blind, parallel‐group study of clinical outcomes in men aged ≥50 years with symptomatic (International Prostate Symptom Score [IPSS]≥12) BPH, with prostate‐specific antigen (PSA) levels of ≥1.5 ng/mL and ≤10 ng/mL, and a prostate volume (PV) of ≥30 mL. ? Eligible patients received tamsulosin 0.4 mg, dutasteride 0.5 mg, or a combination of both. ? The primary endpoint was time to first AUR or BPH‐related surgery. Secondary endpoints included clinical progression of BPH and symptoms. Posthoc analyses of the influence of baseline variables (including age, IPSS health‐related quality of life [HRQL], PV, PSA, IPSS, peak urinary flow rate [Q_max] and body‐mass index [BMI]) on the incidence of AUR or BPH‐related surgery, clinical progression of BPH, and symptoms were performed.

RESULTS

? There were 4844 men in the intent‐to‐treat population. Overall baseline characteristics were similar across all patient groups. ? Regardless of baseline subgroup, the incidence of AUR or BPH‐related surgery was higher in men treated with tamsulosin than in those treated with dutasteride or combined therapy. ? Combined therapy was statistically better than tamsulosin in reducing the risk of AUR or BPH‐related surgery in subgroups of baseline PV > 42.0 mL, in all subgroups of baseline PSA level, and all other baseline subgroups (P≤ 0.001). ? Across treatment groups, the incidence of clinical progression was highest in men with a baseline IPSS of <20 or IPSS HRQL score of <4. The incidence of clinical progression was also higher in men receiving tamsulosin than dutasteride or combined therapy in all baseline subgroups, except for men with a baseline PV of <40 mL. Combined therapy reduced the relative risk (RR) of clinical progression compared with tamsulosin across all baseline subgroups and compared with dutasteride across most baseline subgroups. ? Symptom deterioration was the most common progression event in each treatment group regardless of baseline subgroup, except in those men with an IPSS of ≥20 at baseline. Combined therapy reduced the RR of symptom deterioration compared with tamsulosin across all but one baseline subgroup (the reduction was not significant for men with a baseline PV of <40 mL) and compared with dutasteride in most subgroups.

CONCLUSIONS

? Men with a baseline PV of ≥40 mL and any baseline PSA level of ≥1.5 ng/mL had greater reductions in the RR of AUR or BPH‐related surgery and greater reductions in the RR of clinical progression and symptom deterioration on combined therapy or dutasteride monotherapy than on tamsulosin monotherapy. ? These analyses support the long‐term use of combined therapy with dutasteride plus tamsulosin in men with moderate‐to‐severe BPH symptoms and a slightly enlarged prostate.     

Serum prostate-specific antigen as a predictor of prostate volume in men with benign prostatic hyperplasia

OBJECTIVES: To assess the utility of prostate-specific antigen (PSA) as a predictor of prostate volume by characterizing the relationship between prostate volume and serum PSA in men with symptomatic benign prostatic hyperplasia (BPH) and no evidence of prostate cancer, stratified by decade of life. METHODS: Placebo-controlled multicenter trials in patients with BPH and a safety study in normal young men provided baseline measurements of serum PSA and prostate volume. The analyses included patients with a baseline prostate volume measured by either transrectal ultrasound (TRUS) or magnetic resonance imaging and baseline serum PSA. A common central laboratory was used for all but one of the individual studies; both laboratories used the Hybritech method. Patients 80 years of age or older were excluded. Patients with a baseline serum PSA greater than 10 ng/mL were excluded to reduce the likelihood of including occult prostate cancer cases. The patients in the BPH trials were screened at baseline by digital rectal examination (DRE) and serum PSA. Those with suspicious findings underwent TRUS-guided biopsy; only patients with negative biopsies are included in these analyses. RESULTS: The analyses included 4627 patients, 4448 from the BPH trials and 179 from the safety study. The men in the BPH trials were older (mean age+SE, 63.7+0.10 years) than the men in the safety study (mean age + SE, 30.8+/-0.43), had larger prostates (mean volume+/-SE, 43.7+/-0.38 mL versus 26.3+/-0.49 mL in the safety study), and had higher serum PSA values (mean+/-SE, 2.6+/-0.03 ng/mL versus 0.7+/-0.39 ng/mL in the safety study). The relationship between prostate volume and serum PSA was evaluated using only the BPH trial data. Prostate volume and serum PSA have an age-dependent log-linear relationship (ie, their logarithms are linearly related, and the parameters of the relationship depend on age). Older men tend to have a steeper rate of increase in prostate volume with increasing serum PSA (P < 0.00 for differences between slopes), and there was a slight tendency for PSA density to increase with age. Receiver operating characteristic (ROC) curves were constructed to evaluate the ability of serum PSA to predict threshold prostate sizes in men with BPH. The ROC curve analyses revealed that PSA had good predictive value for assessing prostate volume, with areas under the curve ranging from 0.76 to 0.78 for various prostate volume cutoff points (30, 40, and 50 mL). Conclusions. Prostate volume is strongly related to serum PSA in men with BPH and no evidence of prostate cancer, and the relationship depends on age. Since treatment outcome or risk of long-term complications depend on baseline prostate volume, serum PSA can estimate the degree of prostate enlargement sufficiently accurately to be useful for therapeutic decision making. To achieve a specificity of 70% while maintaining a sensitivity between 65% and 70%, approximate age-specific criteria for detecting men with prostate glands exceeding 40 mL are PSA > 1.6 ng/mL, >2.0 ng/mL, and >2.3 ng/mL for men with BPH in their 50s, 60s, and 70s, respectively.     

Serum prostate-specific antigen as a predictor of prostate volume in Korean men with lower urinary tract symptoms

The aim of the study was to assess the utility of prostate-specific antigen (PSA) as a predictor of prostate volume indexes (total prostate volume (TPV), transition zone volume and transition zone index) in Korean men with lower urinary tract symptoms (LUTS). From September 2003 to April 2006, 3431 patients with LUTS were included in the study; they had a median age of 63.8 years, a median prostate volume of 22.6 ml and a median serum PSA of 1.04 ng/ml. Men with a baseline PSA of >10 ng/ml were excluded, to reduce the likelihood of including occult prostate cancer. Prostate volume indexes and serum PSA levels had an age-dependent log-linear relationship. Receiver operating characteristic curve analysis showed that PSA had good predictive value for various prostate volume indexes thresholds. The approximate age-specific criteria for detecting men with a TPV of >40 ml are PSA levels of 1.20, 1.44 and 1.72 ng/ml for men with LUTS in their sixth, seventh and eighth decades, respectively. The results show that serum PSA identifies Korean men with large prostates reasonably well. Korean men may produce and/or release more PSA per unit prostate volume than white men. The cutoffs for PSA and prostate volume to response to LUTS therapy should be determined in this population.     

Storage (irritative) and voiding (obstructive) symptoms as predictors of benign prostatic hyperplasia progression and related outcomes

OBJECTIVES: To assess the utility of voiding and filling symptom subscores in predicting features of benign prostatic hyperplasia (BPH) progression, including acute urinary retention (AUR) and prostate surgery. METHODS: The Proscar Long-term Efficacy and Safety Study (PLESS) was a 4-year study designed to evaluate the effects of finasteride versus placebo in men with lower urinary tract symptoms (LUTS), clinical evidence of BPH, and no evidence of prostate cancer. A self-administered questionnaire was employed to quantify LUTS at baseline. Receiver operating characteristics (ROC) curves were used to assess baseline characteristics from patients treated with placebo as predictors of outcomes. The characteristics assessed included the overall symptom score (Quasi-AUA SI), separate voiding and filling subscores, prostate volume (PV) and serum prostate-specific antigen (PSA) levels. RESULTS: PV and PSA were superior to the symptom scores at predicting episodes of spontaneous AUR and all types of AUR. The Quasi-AUA SI and the filling and voiding subscores were effective at predicting progression to surgery; however, PSA was more effective at predicting this outcome. To better evaluate symptoms as predictors of surgery, patients who experienced a preceding episode of AUR were excluded from the surgery analysis. In the absence of preceding AUR, the best predictors of future surgery were the Quasi-AUA SI and the filling subscore. CONCLUSIONS: Among men with LUTS, clinical BPH and no history of AUR, the overall symptom score and storage subscore are useful parameters to aid clinicians in identifying patients at risk for future prostate surgery. PV and PSA were the best predictors of AUR, while PSA was the best predictor of prostate surgery (for all indications).     

High serum prostate-specific antigen levels in the absence of prostate cancer in Middle-Eastern men: the clinician's dilemma

OBJECTIVE: To investigate the common causes of total serum prostate-specific antigen (PSA) values of> 10 ng/mL in an Arab population, as in the USA and Europe the risk of prostate cancer is considered high in men with such PSA levels. PATIENTS AND METHODS: Serum total PSA was measured in men presenting to our hospital as part of the investigation for prostate cancer screening and/or in elderly men with prostatism. Men with a serum PSA level of> 10 ng/mL were further investigated by transrectal ultrasonography (TRUS) of the prostate and biopsy of suspicious lesions for histological diagnosis. In addition, the percentage of free PSA, PSA velocity and PSA density were determined. All the patients included in this study were men of Arab origin residing in Kuwait. RESULTS: In all, 1700 men (mean age 55.6 years, range 35-94) were assessed; of these, 161 had a serum PSA of> 10 ng/mL, attributable to benign prostatic hyperplasia (BPH) in 110 (68%), BPH with histological features of prostatitis in 33 (21%) and prostate cancer in 18 (11%). TRUS of the prostate in 143 of the 161 men with either BPH or BPH with prostatitis showed varying grades of intraprostatic calcifications in 22 (15%). Both PSA density and percentage free PSA did not contribute to determining the causes of total PSA levels of> 10 ng/mL. There was a progressive decline in PSA in all patients with BPH and prostatitis, except one who at re-biopsy had prostate cancer (T1N0M0, G1). CONCLUSION: Total PSA values of> 10 ng/mL in Arab men may be a result of BPH, BPH with prostatitis or prostate cancer, in that order. A gradual decline in total PSA (decreased PSA velocity) with time to < 4 ng/mL often confirms the diagnosis of BPH with prostatitis. The percentage of free PSA and PSA density may not be helpful in diagnosing prostate cancer with certainty in these patients. Compared with Caucasians in the USA and Europe, BPH and BPH with prostatitis appear to be more frequent causes of serum PSA levels of> 10 ng/mL in Arab men.     

Associations of lower urinary tract symptoms with prostate-specific antigen levels, and screen-detected localized and advanced prostate cancer: a case-control study nested within the UK population-based ProtecT (Prostate testing for cancer and Treatment) study

OBJECTIVE

To determine associations of lower urinary tract symptoms (LUTS) with prostate‐specific antigen (PSA) levels and screen‐detected localized and advanced prostate cancer.

SUBJECTS AND METHODS

A case‐control study nested within the UK population‐based ProtecT (Prostate testing for cancer and Treatment) study. Men aged 50–69 years were invited for PSA testing and those with a PSA level of ≥3.0 ng/mL were invited for biopsy. We determined whether LUTS were associated with a PSA level of ≥3.0 ng/mL and prostate cancer using logistic regression models adjusted for age, family history of prostate cancer and PSA level as appropriate. Areas under receiver operating characteristic curves (AUC) were compared between models with and without symptoms.

RESULTS

In all, 65 871 men had a PSA test: 7251 had a PSA level of ≥3.0 ng/mL including 2467 subsequently diagnosed with prostate cancer (2119 localized, 348 advanced). LUTS were positively associated with a PSA level of ≥3.0 ng/mL: odds ratios (ORs) were 1.18 (95% confidence interval, CI 1.01–1.38), 1.69 (95% CI 1.32–2.16), and 1.60 (95% CI 1.33–1.93) for daytime urination frequency (hourly vs less frequent), urgency and hesitancy (most/all the time vs never), respectively. LUTS among men with a PSA level of ≥3 ng/mL were negatively associated with prostate cancer: ORs were 0.44 (95% CI 0.22–0.83), 0.74 (95% CI 0.63–0.87), and 0.83 (95% CI 0.73–0.94) for nocturia (4+ vs 0), leakage and hesitancy (occasionally/sometimes vs never), respectively. LUTS improved the prediction of a PSA level of ≥3.0 ng/mL (AUC 0.635 vs 0.606, P < 0.001) and prostate cancer (AUC 0.661 vs 0.638; P < 0.001).

CONCLUSIONS

A history of LUTS before PSA testing marginally improves the prediction of an individual’s risk for prostate cancer; men with a PSA level of ≥3 ng/mL and LUTS were more likely to be diagnosed with benign disease than prostate cancer.     

Serum prostate-specific antigen to predict the presence of bladder outlet obstruction in men with urinary symptoms

OBJECTIVE: To determine whether prostate specific antigen (PSA) level can usefully predict or exclude bladder outlet obstruction (BOO), in men with lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: A cohort of men from 1996 to 1999 who had LUTS caused by BPH was evaluated by serum PSA and pressure-flow urodynamic studies, and a blinded comparison made. The settings were teaching hospitals in London, UK and L'Aquila, Italy. Men (302) were referred by primary-care practitioners with LUTS and a PSA of < 10 ng/mL. Regression analysis was used to predict the extent of BOO, and create likelihood ratios and predictive values for BOO according to the PSA value. RESULTS: PSA was significantly associated with BOO (P < 0.001; r2 0.07), with significant likelihood ratios altering the probability of BOO. If the PSA was > 4 ng/mL, mild or definite BOO was likely (89%), whereas if the PSA was <2 ng/mL, there was about a one-third chance each of no, mild and definite BOO. CONCLUSION: High PSA levels in patients with LUTS are significantly associated with BOO; low PSA levels mean that definite BOO is unlikely.     

Urinary PSA: a potential useful marker when serum PSA is between 2.5 ng/mL and 10 ng/mL

Introduction

Our objective was to evaluate the usefulness of urinary prostate specific antigen (PSA) in the differential diagnosis of benign prostatic hyperplasia (BPH) and prostate cancer.

Methods

We undertook a prospective study and obtained informed consent from 170 men. They provided blood samples to measure serum PSA and 50 mL of first-voided urine to measure urinary PSA. Seventy-seven men were diagnosed with BPH; 42 patients had newly diagnosed prostate cancer; and 51 were selected as age-matched control subjects. Data were analyzed using Wilcoxon signed rank tests, receiver operating characteristic (ROC) curves and logistic regression.

Results

Prostate volume was 35 cm³ and 45 cm³ (p < 0.05), serum PSA was 9.7 ng/mL and 4.5 ng/mL (p < 0.001) and PSA density was 0.28 and 0.11 (p < 0.01) for prostate cancer and BPH patients, respectively. Overall, urinary PSA was not significantly different, but PSA ratio (urinary:serum) was significantly different at 6.7 and 30.6 (p < 0.001) for prostate cancer and BPH patients, respectively. A subgroup with serum PSA between 2.5 ng/mL and 10.0 ng/mL was selected and urinary PSA was significant: 52.6 ng/mL (n = 29) and 123.2 ng/mL (n = 35) (p < 0.05) for prostate cancer and BPH patients, respectively. PSA ratios were also significant (p = 0.007). ROC curves identified a cutoff for urinary PSA at > 150 ng/mL, with a sensitivity of 92.5%. When comparing prostate cancer patients with age-matched control subjects, serum PSA, urinary PSA and PSA ratio were different (p = 0.004).

Conclusion

Our study supports urinary PSA as a useful marker in the differential diagnosis of prostate cancer and BPH, especially when serum PSA is between 2.5 ng/mL and 10 ng/mL. Low urinary PSA and PSA ratios point toward prostate cancer. A urinary PSA threshold of > 150 ng/mL may be used to decrease the number of prostatic biopsies.     

Prostate-specific antigen 1.5-4.0 ng/mL: a diagnostic challenge and danger zone

Study Type – Prognosis (inception cohort) Level of Evidence 1b What’s known on the subject? and What does the study add? Large population screening trials like the ERSPC, PCPT and PLCO have noted that men with seemingly low PSA (even as low as 0.5 ng/dL) still can have prostate cancer. Despite these findings, PSA is still predominantly used as a current indicator for possible presence of prostate cancer rather than also serving as a prognostic marker. This study examines a larger number of men in a diverse US population to determine the prognostic value of a man’s baseline or first PSA.

OBJECTIVES

? To assess the value of a PSA threshold of 1.5 ng/mL as a predictor of increased prostate cancer risk over a four‐year period based on a man’s first PSA test, including racial differences. ? To review the risk of progression of benign prostatic hyperplasia (BPH) based on a similar PSA threshold.

PATIENTS AND METHODS

? A retrospective review involving 21 502 men from a large Midwestern health system was performed. ? Men at least 40 years old with baseline PSA values between 0 and 4.0 ng/mL and at least four years of follow‐up after initial PSA test were included. ? Optimal PSA threshold and predictive value of PSA for development of prostate cancer were calculated.

RESULTS

? Prostate cancer rates were 15‐fold higher in patients with PSA ≥1.5 ng/mL vs patients with PSA <1.5 ng/mL (7.85% vs 0.51%). ? African American patients with baseline PSA <1.5 ng/mL faced prostate cancer rates similar to the whole study population (0.54% vs 0.51%, respectively), while African American patients with PSA 1.5–4.0 ng/mL faced a 19‐fold increase in prostate cancer.

CONCLUSION

? Both Caucasian and African American men with baseline PSA values between 1.5 and 4.0 ng/mL are at increased risk for future prostate cancer compared with those who have an initial PSA value below the 1.5 ng/mL threshold. ? Based on a growing body of literature and this analysis, it is recommended that a first PSA test threshold of 1.5 ng/mL and above, or somewhere between 1.5 and 4.0 ng/mL, represent the Early‐Warning PSA Zone (EWP Zone). ? This should serve to inform patients and clinicians alike to future clinical activities with respect to prostate cancer and BPH.     

Non-steroidal anti-inflammatory drug use and the risk of benign prostatic hyperplasia-related outcomes and nocturia in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Study Type – Therapy (cohort) Level of Evidence 4 What's known on the subject? and What does the study add? Accumulating evidence suggests that inflammation may contribute to the development of BPH and LUTS. Therefore, it is plausible that anti‐inflammatory agents, such as aspirin and other NSAIDs, may reduce the risk of BPH/LUTS, as was observed in a recent analysis of daily aspirin use and BPH/LUTS risk in the Olmsted County Study of Urinary Symptoms and Health Status in Men. The present study, conducted in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, found no association for recent aspirin or ibuprofen use with the risk of BPH/LUTS.

OBJECTIVE

• ? To investigate the relationship between non‐steroidal anti‐inflammatory drug (NSAID) use and the incidence of benign prostatic hyperplasia (BPH)‐related outcomes and nocturia, a lower urinary tract symptom (LUTS) of BPH, in light of accumulating evidence suggesting a role for inflammation in BPH/LUTS development.

PATIENTS AND METHODS

• ? At baseline, participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial completed questions on recent, regular aspirin and ibuprofen use, BPH surgery, diagnosis of an enlarged prostate/BPH, and nocturia. Participants in the intervention arm also underwent a digital rectal examination (DRE), from which prostate dimensions were estimated, as well as a prostate‐specific antigen (PSA) test. Only participants in the intervention arm without BPH/LUTS at baseline were included in the analysis (n= 4771).
• ? During follow‐up, participants underwent annual DREs and PSA tests, provided annual information on finasteride use, and completed a supplemental questionnaire in 2006–2008 that included additional questions on diagnosis of an enlarged prostate/BPH and nocturia.
• ? Information collected was used to investigate regular aspirin or ibuprofen use in relation to the incidence of six BPH/LUTS definitions: diagnosis of an enlarged prostate/BPH, nocturia (waking two or more times per night to urinate), finasteride use, any self‐reported BPH/LUTS, prostate enlargement (estimated prostate volume ≥30 mL on any follow‐up DRE) and elevation in PSA level (>1.4 ng/mL on any follow‐up PSA test).

RESULTS

• ? Generally, null results were observed for any recent, regular aspirin or ibuprofen use (risk ratio = 0.92–1.21, P= 0.043–0.91) and frequency of use (risk ratios for one category increase in NSAID use = 0.98–1.11, P‐trends = 0.10–0.99) with incident BPH/LUTS.

CONCLUSION

• ? The findings obtained in the present study do not support a protective role for recent NSAID use in BPH/LUTS development.

     

Changes in prostate volume in Japanese patients with benign prostatic hyperplasia: Association with other urological measures and risk of surgical intervention

Objectives:   To evaluate changes in prostate volume (PV) and its association with selected urological measures and risk of surgical intervention in Japanese men with benign prostatic hyperplasia (BPH).
Methods:   The medical records of all consecutive urologist-diagnosed BPH patients of ≥40 years old who attended any of four urology clinics in Japan during January 2004–June 2006 were reviewed. Both cross-sectional and longitudinal data were captured to analyze baseline correlations among urological measures, to evaluate the longitudinal changes in PV and selected urological measures, and to examine the predictors of surgical intervention.
Results:   The follow-up period was 2.8 years. Mean PV and mean prostate-specific antigen (PSA) of 1331 eligible patients were 34.0 mL and 4.0 ng/mL, respectively. Both measures increased directly with age. Baseline PV correlated with residual urine volume (r = 0.18, P  < 0.05) and PSA (r = 0.41, P  < 0.001). Among 319 patients who had more than one PV measurement, PV increased in 51% of patients, remained the same in 28% and decreased in 21%. Use of α-blockers at baseline and during follow up was not associated with PV change. Patients who had a PV ≥30 mL, a severe International Prostate Symptom Score and a PSA level ≥1.5 ng/mL at baseline, were more likely to have surgical intervention during the follow-up period.
Conclusions:   Predictors generated in this study may help to identify a subset of BPH patients at high risk of surgical intervention.     

前列腺体积与良性前列腺增生老年患者糖尿病之间的关系研究

目的 探讨前列腺体积(PV)与良性前列腺增生(BPH)老年患者糖尿病(DM)之间的关系.方法 选取2012年4月至2015年6月于本院诊断为良性前列腺增生老年(年龄≥60岁)患者115例为本研究试验对象.记录其血清甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、空腹胰岛素(FINS)、糖化血红蛋白(HbAlc)、空腹血糖(FBG)及前列腺特异性抗原(PSA)等生化指标.结果 BPH合并DM组患者与BPH组相比PV更大[(51.5±19.1)和(41.2±10.1 mL)],PSA水平[(3.2±1.1)和(1.9±0.6 ng/mL)]及IP-SS分数更高[(12.5±1.3)和(8.9±1.1)],且组间差异具有显著统计学意义(P＜0.05).与正常FBG组相比,异常FBG组患者的PV、PSA水平均显著增加(P＜0.05).异常HbAlc组患者的PV也明显增加.另外,FINS组和IR组的PV及下尿路症状(LUTS)持续时间均分别高于正常FINS组和胰岛素敏感组.逻辑回归分析显示FBG和FINS是BPH的危险因素.结论 糖尿病与前列腺体积之间具有显著相关性,可影响良性前列腺增生的发生发展.     

Prostate-specific antigen changes as a result of chlormadinone acetate administration to patients with benign prostatic hyperplasia: A retrospective multi-institutional study

BACKGROUND: Antiandrogens used to treat benign prostatic hyperplasia (BPH) may affect the diagnosis of prostate cancer by decreasing serum prostate-specific antigen (PSA) values. We conducted a retrospective survey of BPH patients treated with chlormadinone acetate (CMA) and analysed the effect of CMA on their PSA values. METHODS: A chart-based, retrospective, multi-institutional survey of clinically diagnosed patients with BPH who had been treated with CMA (Prostal; 50 mg/day) was conducted. The patients were divided into three groups according to their baseline PSA values: <4 ng/mL, Group I; >or=4 ng/mL and <10 ng/mL, Group II; and >or=10 ng/mL, Group III. The changes in the PSA values from baseline after 16, 26, and 52 weeks of CMA therapy were predicted using a nonlinear regression model analysis. RESULTS: Data from 192 of the 303 enrolled patients were analysed. The predicted percent changes from baseline among all patients after 16, 26, and 52 weeks of treatment were -49.6%, -49.8%, and -49.9%, respectively. The corresponding values were -42.4%, -43.7% and -43.8% in Group I; -57.4%, -58.4% and -58.5% in Group II; and -50.6%, -50.6% and -50.6% in Group III, respectively. CONCLUSION: The PSA values reached a nadir, approximately -50% of the baseline, after 16 weeks of CMA administration and remained at the same level thereafter. When CMA is used to treat BPH patients, the possibility of abnormal increases in PSA associated with prostate cancer must be considered; if prostate cancer is suspected, prompt testing, including a biopsy, should be performed.     

Prostate-specific antigen (PSA) and PSA velocity for prostate cancer detection in men aged <50 years

OBJECTIVE: To identify threshold values of prostate-specific antigen (PSA) levels and PSA velocity (PSAV) to optimize the assessment of the risk of prostate cancer in young men, as prostate cancer is detected increasingly in men aged <50 years. PATIENTS AND METHODS: Data for a group of 12 078 men, including 1622 with prostate cancer, were retrieved from the Duke Prostate Center Database. Based on the latest date for a PSA assay, these men were divided into two age groups of <50 and >/= 50 years, with 904 and 11 174 men in each group, respectively. Receiver operating characteristic curves (ROC) of PSA and PSAV were calculated and the cancer risk was assessed. RESULTS: The prevalence of prostate cancer was 4.4% (40 men) for men aged <50 years and 14.2% (1582 men) for men aged >/= 50 years. For the group with cancer the median PSA in men aged <50 years was significantly lower than that in men aged >/= 50 (1.3 vs 6.3 ng/mL, P < 0.001). ROC curves of PSA and PSAV showed a breakpoint at a PSA level of 2.3 ng/mL and a PSAV of 0.60 ng/mL/year for men aged <50 years. Both the sensitivity and specificity in the younger group at a PSA level of 2.5 ng/mL were higher than in the older group. CONCLUSIONS: In men aged <50 years the operating characteristics of PSA are more sensitive and specific than in older men. Diagnostic PSA levels in men aged <50 years are significantly lower than suggested by guidelines. Using a 2.0-2.5 ng/mL PSA level threshold for biopsy in men aged <50 years and a PSAV threshold lower than the traditional 0.75 ng/mL/year is reasonable in contemporary practice. Further studies are warranted to validate these thresholds.     

Ethnic differences in the age-related distribution of serum prostate-specific antigen values: a study in a healthy Korean male population

Objectives. To further improve the use of prostate-specific antigen (PSA) as a screening test for prostate cancer in Asian countries, we sought to establish the normal distribution of serum PSA values in Korean men, because, until recently, studies conducted to establish normal serum PSA values have involved few Asian populations.Methods. Between May 1995 and June 1997, 5805 healthy Korean men 30 to 79 years old who visited our hospital for a routine health checkup were entered into a prospective study of early screening for prostate cancer. All men underwent detailed clinical examinations, including a digital rectal examination and serum PSA determination. All men who were more than 50 years old with abnormal digital rectal examination findings and/or an elevated serum PSA level (greater than 4.0 ng/mL) also underwent transrectal ultrasound-guided sextant biopsy. Four were found to have cancer and were excluded from the analysis.Results. The median serum PSA concentration (5th to 95th percentile range) was 0.8 ng/mL (0.2 to 1.8) for patients 30 to 39 years old (n = 1382); 0.8 ng/mL (0.2 to 2.0) for patients 40 to 49 years old (n = 1776); 0.9 ng/mL (0.2 to 2.4) for those 50 to 59 years old (n = 1775); 1.0 ng/mL (0.2 to 3.9) for men 60 to 69 years old (n = 746); and 1.3 ng/mL (0.5 to 6.3) for patients 70 to 79 years old (n = 122). The serum PSA concentration correlated with age (P <0.001), with an increase by approximately 1.2% annually, although the statistical correlation was weak (r = 0.16). Almost no change occurred in the median serum PSA value in patients 50 years old or younger; a gradual increase was observed in patients older than 50. In those 50 years old or older, the median and 95th percentile serum PSA values for Korean men were lower than those for white men.Conclusions. Contrary to earlier observations that the serum PSA level strongly correlates with age, the influence of age on serum PSA was found to be weaker in this study. Moreover, the results also demonstrated that the distribution of the serum PSA level differs along ethnic lines. The cutoff value for serum PSA in mass screening for prostate cancer should be adjusted in nonwhite races.     

BPH相关LUTS与各临床影响因素关系的研究

目的 研究前列腺增生症(BPH)相关下尿路症状(LUTS)与各临床影响因素的关系.方法 选择本院收治的146例BPH患者为研究对象,采用回顾性调查法分别调查本组患者的病历资料,包括年龄、病程、前列腺体积、前列腺特异抗原(PSA)、前列腺增生家族史、情绪、血清雌激素等.以患者下尿路症状严重程度为因变量,以可能导致患者下尿路症状加重的各类因素为自变量,先进行单因素分析,单因素分析后再运用Logistic回归分析工具进行多因素分析.结果 单因素分析结果显示,年龄、最大尿流量、PSA、HAMD评分及血清雌激素均是影响BPH相关LUTS严重程度的重要因素(P＜0.05);Logistic多因素回归分析结果显示,年龄、最大尿流量、PSA及血清雌激素是影响BPH相关LUTS严重程度的独立危险因素(P＜0.05).结论 年龄增长、最大尿流量＜5mL/s、PSA升高及血清雌激素升高均是加重前列腺增生症相关下尿路症状严重程度的重要危险因素.     

Serum prostate-specific antigen as a predictor of prostate volume and lower urinary tract symptoms in a community-based cohort: a large-scale Korean screening study

The aim of this study is to assess the ability of serum prostate-specific antigen (PSA) to predict prostate volume (PV) and lower urinary tract symptoms (LUTS) represented by the international prostate symptom score (IPSS). From January 2001 to December 2011, data were collected from men who first enrolled in the Korean Prostate Health Council Screening Program. Patients with a serum PSA level of >10 ng ml⁻¹ or age <40 years were excluded. Accordingly, a total of 34 857 men were included in our study, and serum PSA, PV and the IPSS were estimated in all patients. Linear and age-adjusted multivariate logistic analyses were used to assess the potential association between PSA and PV or IPSS. The predictive value of PSA for estimating PV and IPSS was assessed based on the receiver operating characteristics-derived area under the curve (AUC). The mean PV was 29.9 ml, mean PSA level was 1.49 ng ml⁻¹ and mean IPSS was 15.4. A significant relationship was shown between PSA and PV, and the IPSS and PSA were also significantly correlated after adjusting by age. The AUCs of PSA for predicting PV >20 ml, >25 ml and >35 ml were 0.722, 0.728 and 0.779, respectively. The AUCs of PSA for predicting IPSS >7, >13 and >19 were 0.548, 0.536 and 0.537, respectively. Serum PSA was a strong predictor of PV in a community-based cohort in a large-scale screening study. Although PSA was also significantly correlated with IPSS, predictive values of PSA for IPSS above the cutoff levels were not excellent. Further investigations are required to elucidate the exact interactions between PSA and LUTS and between PSA and PV in prospective controlled studies. Such studies may suggest how PSA can be used to clinically predict PV and the IPSS.     

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

OBJECTIVE: 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. SUBJECTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

Age-specific reference levels of serum prostate-specific antigen and prostate volume in healthy Arab men

OBJECTIVE; To determine age-specific reference ranges for serum prostate-specific antigen (PSA) concentration and prostate volumes in a population of healthy Arab men. SUBJECTS AND METHODS: Blood samples were taken from 396 healthy Arab men (from Kuwait and Oman) aged 15-79 years and from across the social spectrum. Men aged >40 years had a digital rectal examination and transrectal ultrasonography of the prostate to determine prostate volume. The serum PSA level was measured using commercial kits, and age-specific ranges for PSA levels and prostate volume determined. RESULTS: The serum PSA ranges (ng/mL) for each age range in Arab men were: 40-49 years, 0-0.9; 60-69, 0-2.7; 70-79, 0-5.5 ng/mL; the respective prostate volumes were 8-22, 9-30 and 10-33 mL. The serum PSA level and prostate volume correlated with age (P < 0.001). Arab men had lower serum PSA levels and prostate volumes than those reported for Caucasians, but similar to those reported for Asians (Japanese and Chinese). CONCLUSION: These results indicate that Arab men have lower PSA levels and prostate volumes than Caucasians. The levels are slightly lower than those reported in the Japanese and, as in the Japanese, low PSA levels and small prostate volumes might be related to the low incidence of clinical prostate cancer in Arab men.