Raised Prostate-specific Antigen Levels Research Articles

Serum Levels of Prostate Specific Antigen and Specific Reproductive Hormones Among Male Subjects with Benign Prostate Hyperplasia in Port Harcourt, Nigeria

Benign prostate hyperplasia (BPH) is a medical condition in elderly men in which there is proliferation and enlargement of the prostate gland. This study evaluated the levels of male reproductive hormones among subjects with BPH. The study involved 150 subjects aged 40 years and above, comprising 80 BPH subjects attending the urology clinic and 70 control subjects. Five millilitres (5ml) of venous blood were collected from each subject into plain bottles for the determination of prostate-specific antigen (PSA), testosterone, prolactin, and estradiol, using the ELISA technique. The mean values of PSA (16.68±10.96 ng/ml), estradiol (71.03±18.56 pg/ml) and for the BPH subjects and prolactin (9.38±4.51 ng/ml) were significantly higher compared to the mean values of PSA (0.48±0.25ng/ml), estradiol (51.33±7.13npg/ml) and prolactin (6.92±1.93ng/ml) of the control subjects. However, the mean testosterone value of the BPH subjects (5.02±1.93 ng/ml) was significantly lower than the mean value for the control (6.57±3.48ng/ml). The BPH who used to consume alcohol had higher PSA (24.26±8.33ng/ml) and testosterone (7.68±3.41ng/ml) compared to the PSA (16.34±3.22ng/ml) and testosterone (4.95±3.62ng/ml) of those who never consumed alcohol. The BPH had significantly altered hormone parameters as well as raised PSA levels. Including hormonal parameters in diagnosing and managing BPH could be an important consideration in our population.

Utility of serum biomarkers for predicting cancer in patients with previous negative prostate biopsy.

To review the role of serum biomarkers: prostate-specific antigen (PSA), PSA density (PSAD), free:total PSA ratio, prostate health index (PHI) and PHI density (PHID), along with magnetic resonance imaging (MRI) for identification of clinically significant prostate cancer (PCa), comparing their utility in patients with persistently raised PSA levels after a prior negative prostate biopsy (PNB). In this single-centre prospective observational study conducted from September 2015 to October 2020, patients underwent a saturation biopsy via the transperineal route. If a Prostate Imaging Reporting and Data System version 2 (PIRADS) 3 and above lesion was seen on MRI, targeted biopsies were also obtained. Information on clinical history, lesion characteristics, PIRADS classification and follow-up was collected. The sensitivity, specificity and area under curve (AUC) for each of the biomarkers were calculated. 351 men underwent saturation biopsy with or without targeted biopsies. 103 patients had a PNB. Among this PNB cohort, 43 (41.7%) men had a benign outcome, while 60 (58.3%) men had histopathologically diagnosed PCa, of which 41 (39%) were clinically significant. All patients underwent multiparametric MRI scans prior to biopsy. Within this cohort, PHI and PHID had the best abilities to predict for clinically significant PCa with an AUC of 0.73 and 0.70 respectively, compared to 0.65 for PSAD, 0.34 for free:total PSA and 0.56 for PSA. A significant proportion of patients are diagnosed with PCa after a PNB. This study shows that PHI and PHI densities may be suitable adjuncts predicting for clinically significant PCa in patients with PNB.

Evaluation of 18F-PSMA-1007 PET/CT in prostate cancer patients with biochemical recurrence after radical prostatectomy

PurposeProstate-specific membrane antigen (PSMA) ligands targeting has shown promising results in staging of prostate cancer (PCa). The aim of present study was to evaluate the value of 18F-PSMA-1007 PET/CT in PCa patients with biochemical recurrence. Methods71 patients with PCa after radical prostatectomy (RP) were included in the present study. Median prostate-specific antigen (PSA) level was 1.27 ng/mL (range 0.01–67.40 ng/mL, n = 69). All patients underwent whole-body PET/CT imaging after injection of 333±38 MBq 18F-PSMA-1007. The distribution of PSMA-positive lesions was assessed. The influence of PSA level, androgen deprivation therapy and primary Gleason score on PSMA-positive finding and uptake of 18F-PSMA-1007 were evaluated. Results56 (79%) patients showed at least one pathological finding on 18F-PSMA-1007 PET/CT. The rates of positive scans were 50%, 80%, 100%, 100% among patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and >2.0 ng/mL, respectively. The median Gleason score was 8 (range 7–10), and higher Gleason score (≤7 vs. ≥8) leads to higher detection rates (58.3% (14/24) vs. 88.9% (32/36), P = 0.006). The median SUVmax of positive findings in patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and >2.0 ng/mL were 4.51, 4.27, 11.50 and 14.08, respectively. The median SUVmax in patients with PSA level >2.0 ng/mL was significantly higher than that in patients with PSA ≤2.0 ng/mL (14.08 vs. 6.13, P<0.001). Conclusion18F-PSMA-1007 PET/CT demonstrated a high detection rate for patients with a raised PSA level after radical prostatectomy even in patients with extremely low PSA level (eg. PSA level ≤0.5 ng/mL), which was essential for further clinical management for PCa patients.

Histopathology, pharmacotherapy, and predictors of prostatic malignancy in elderly male patients with raised prostate-specific antigen levels - A prospective study.

Background:Prostate cancer is the second most common cancer among adult men in the world, and the diagnosis requires biopsy. Prostate-specific antigen (PSA) test along with digital rectal examination (DRE) increases the detection rate of prostate cancer than DRE alone. The objective of this study was to correlate serum PSA level with histopathological diagnosis, identify the predictors of malignancy, and describe the pharmacotherapy of patients with serum PSA levels >4 ng/ml.Materials and Methods:This was a hospital-based observational study done among patients who presented with lower urinary tract symptoms and PSA levels >4 ng/ml who were planned to undergo prostatic biopsy. DRE followed by transrectal ultrasound (TRUS) assessment and guided sextant (6-core) prostatic biopsy was performed.Results:One hundred and four patients were screened and 87 were included. Nineteen patients were diagnosed with malignancy, and among them, eight had bone metastasis. Spearman's correlation coefficient between PSA and malignancy was 0.449 (P ≤ 0.001). Multivariate analysis suggested that the factors (adjusted odds ratio; 95% confidence interval; P value) such as increasing age (1.127; 1.013, 1.253; 0.027), nodular prostate (22.668; 4.655, 110.377; P < 0.001), and PSA (1.034; 1.004, 1.064; 0.024) were significant predictors of prostate cancer. All patients with benign prostatic hyperplasia were advised a combination therapy with 5-alpha reductase inhibitor and selective alpha-1 receptor antagonist while those with malignancy were prescribed androgen deprivation therapy with antiosteoporosis therapy.Conclusion:In elderly patients with raised PSA levels or suspicious DRE findings, TRUS-guided prostate is recommended to rule out malignancy and plan appropriate management.

Role of Transrectal Ultrasound Elastography in the Diagnosis of Prostate Carcinoma.

Background:The purpose of this study was to evaluate the diagnostic value of transrectal real- time strain elastography (RTE) in identifying prostatic carcinoma (PCa).Methods:60 patients suspected of having PCa based on abnormal digital rectal examination and raised prostate specific antigen levels underwent transrectal ultrasound (TRUS), color Doppler (CD) and RTE. Elastograms were scored on a five point scale based on distribution of strain in relation to hypoechoic area on TRUS. Twelve core systematic biopsy as well as targeted biopsy was performed from suspicious areas on TRUS and RTE. Diagnostic performance of sonoelastography was evaluated using histopathology as reference standard.Results:Histopathology revealed cancer in 28 out of 60 patients (47%) studied. Gleason score ranged from 6 to 9. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of TRUS in detecting prostate cancer were 78.57%, 81.25%, 78.57%, and 81.25%, respectively. On CD evaluation 87.5% (n = 28) of benign lesions showed symmetric, radial flow compared to 14.3% (n = 4) of malignant lesions (P < 0.0001). The sensitivity and specificity of RTE was 89.29% and 56.25% with PPV and NPV being 58.13% and 82.35%, respectively. Higher elastography score was found to be significantly associated with malignant histopathology (P = 0.004). Cancer detection rate with RTE was greater for tumors with higher Gleason score.Conclusion:RTE was found to have better sensitivity than TRUS as well as combination of TRUS and CD. Although less specific, RTE can be an effective adjuvant tool to TRUS for guidance of biopsy and improve detection rate of PCa.

Correlation of prostate specific antigen level with histopathological findings in patients with prostatic disease

Background: Carcinoma of prostate is one of the common tumors of old age in men. Although there is great apprehension in these patients when they are associated with even mild increase in the prostate specific antigen level (PSA) which can be seen in various benign lesions of prostate. With digital rectal examination (DRE), prostate specific antigen (PSA) remains a major screening tool for early detection of prostate cancer. Materials and method: The study includes 150 cases who presented clinically as prostatic lesions and in whom the PSA levels and tissue biopsy was available and was further correlated among spectrum of prostatic disease. Results: All cases with abnormal DRE were turn out to be malignant lesion on biopsy and was found that the cut off of PSA level for malignancy was 19.5ng/ml. The median PSA levels for benign prostatic hyperplasia (BPH), prostatitis, prostate intraepithelial neoplasia (PIN) and adenocarcinoma is 5ng/ml, 10 ng/ml, 14 ng/ml and 81ng/ml respectively. Statistically there was no significant difference of the PSA levels between low grade prostate intraepithelial neoplasm and high grade. Conclusion: In Benign prostatic lesion, PSA level ranges between 0 to 4.0ng/ml. The cut off value of 19.5ng/ml of PSA is most sensitive and specific for the detection of malignant lesion in the prostate. In addition to elevated level of more than 4.0ng/ml and abnormal DRE with TURP biopsy is most useful and accurate diagnostic method for prostatic lesions. All raised PSA levels cases were not malignant thus it is required to use this biochemical marker judiciously to minimize the apprehension among these patients.

Incorporating Known Genetic Variants Does Not Improve the Accuracy of PSA Testing to Identify High Risk Prostate Cancer on Biopsy.

IntroductionProstate-specific antigen (PSA) testing is a widely accepted screening method for prostate cancer, but with low specificity at thresholds giving good sensitivity. Previous research identified four single nucleotide polymorphisms (SNPs) principally associated with circulating PSA levels rather than with prostate cancer risk (TERT rs2736098, FGFR2 rs10788160, TBX3 rs11067228, KLK3 rs17632542). Removing the genetic contribution to PSA levels may improve the ability of the remaining biologically-determined variation in PSA to discriminate between high and low risk of progression within men with identified prostate cancer. We investigate whether incorporating information on the PSA-SNPs improves the discrimination achieved by a single PSA threshold in men with raised PSA levels.Materials and MethodsMen with PSA between 3-10ng/mL and histologically-confirmed prostate cancer were categorised as high or low risk of progression (Low risk: Gleason score≤6 and stage T1-T2a; High risk: Gleason score 7–10 or stage T2C). We used the combined genetic effect of the four PSA-SNPs to calculate a genetically corrected PSA risk score. We calculated the Area under the Curve (AUC) to determine how well genetically corrected PSA risk scores distinguished men at high risk of progression from low risk men.ResultsThe analysis includes 868 men with prostate cancer (Low risk: 684 (78.8%); High risk: 184 (21.2%)). Receiver operating characteristic (ROC) curves indicate that including the 4 PSA-SNPs does not improve the performance of measured PSA as a screening tool for high/low risk prostate cancer (measured PSA level AU C = 59.5% (95% CI: 54.7,64.2) vs additionally including information from the 4 PSA-SNPs AUC = 59.8% (95% CI: 55.2,64.5) (p-value = 0.40)).ConclusionWe demonstrate that genetically correcting PSA for the combined genetic effect of four PSA-SNPs, did not improve discrimination between high and low risk prostate cancer in men with raised PSA levels (3-10ng/mL). Replication and gaining more accurate estimates of the effects of the 4 PSA-SNPs and additional variants associated with PSA levels and not prostate cancer could be obtained from subsequent GWAS from larger prospective studies.

Potential utility of cancer-specific biomarkers for assessing response to hormonal treatments in metastatic prostate cancer.

Prostate cancer is the second leading cause of cancer death in men and there is an urgent clinical need to improve its detection and treatment. The introduction of prostate-specific antigen (PSA) as a biomarker for prostate cancer several decades ago represented an important step forward in our ability to diagnose this disease and offers the potential for earlier and more effective treatment. PSA measurements are now routinely conducted alongside digital rectal examination, with raised PSA levels leading to biopsy. PSA is also used to monitor disease and assess therapeutic response. However, there are some important limitations to its use, not least its lack of specificity for prostate cancer, and increased PSA screening may have resulted in overdiagnosis and overtreatment of early, low-risk prostate cancer. Therefore, there is a need for more specific and sensitive biomarkers for the diagnosis and monitoring of prostate cancer and treatment response; in particular, biomarkers of response to hormonal treatments in prostate cancer and predictive biomarkers to identify who is most likely to respond to these treatments. Here we review the current utilization of PSA and data on potentially more specific and sensitive biomarkers for the diagnosis and monitoring of prostate cancer: prostate cancer antigen 3 (PCA3) and the TMPRSS2-ERG fusion gene. A description of the design of an ongoing study of the 6-month extended release formulation of leuprorelin acetate (Eligard(®) 45 mg) will provide preliminary data on the potential utility of these new biomarkers for detecting therapeutic response after hormonal therapy.

Fehlerkriterien bei der PSA-Diagnostik

The widespread use of prostate-specific antigen (PSA) determination in the diagnosis of prostate cancer has proved to be generally beneficial; however, as a result expert commissions, arbitration committees and the courts have had to deal with an increased number of suspected treatment errors. As a follow-up to the previous report on the decisions made by expert commissions, this paper deals with recent developments and their assessment. The procedures followed for assessment have been extensively described in the previous paper. The criteria for assessment of disputed treatment were and are the accepted standards (i.e. the standards applicable to medical specialists) and the quality of care applied in accordance with the pertinent definitions. In the period from 2005 to 2011 (i.e. 7 years) errors in medical treatment were determined in connection with PSA determinations in 22 out of the 37 cases reviewed, i.e. 71%. These were subdivided into 3 cases from general practitioners, 5 cases from specialists in internal medicine and 15 cases from urologists (in 1 case 2 different doctors were involved). They were faulted for omitting a follow-up biopsy of the prostate. In 12 cases this involved PSA values above the recommended cut-off level without suspicious palpation results, in 7 cases raised PSA levels with suspicious palpation findings, in 2 cases suspicious palpation findings without raised PSA and in 1 case the omission of both palpation and PSA determination. An error in treatment was negated if the PSA value was below the recommended cut-off value or had fallen below it again subsequently (two cases each), if follow-up prostate biopsy was recommended and documented following the determination of raised PSA and/or suspicious palpation findings (three cases) or if follow-up treatment was rejected in spite of a documented recommendation (one case). Treatment errors in association with PSA determinations can therefore be uniformly and plausibly assessed using objective criteria and can thus be avoided.

41 The protective antimicrobial effect of raised prostate specific antigen levels during male urinary tract infection

41 The protective antimicrobial effect of raised prostate specific antigen levels during male urinary tract infection

Antibiotics and observation have a similar impact on asymptomatic patients with a raised PSA

• To compare the influence of a 4-week course of empirical antimicrobial therapy or observation on the prostate-specific antigen (PSA) levels of asymptomatic patients with a raised baseline PSA. • To identify whether a decrease in PSA can predict the risk of prostate cancer (PCa) detection on prostate biopsy. • Patients were referred to our ambulatory centre because of a raised PSA level (>2.5 ng/mL) with a normal digital rectal examination. A 12-core prostate biopsy was indicated in these patients and they were offered antibiotic treatment with levofloxacin 500 mg daily for 30 days. • Patients who did not agree to use antibiotics but who still showed interest in participating underwent simple observation, serving as controls. • Total and free PSA levels at baseline and after 45 days were measured. Variation in PSA level was calculated. • All patients underwent a 12-core prostate biopsy 6 weeks after the initial visit. • In all, 245 men were enrolled, but 43 were lost due to follow-up. A total of 145 patients who used antibiotics and 57 controls were included in the analysis. • The median baseline PSA levels were 7.6 and 7.7 ng/mL in the antibiotic and control groups, respectively, with median follow-up levels of 6.8 and 7.0 ng/mL. The follow-up PSA level was significantly lower than the initial PSA level (P = 0.009). • Mean absolute and percentage variation in PSA level were similar in both groups (P = 0.828 and 0.128, respectively). • The overall PCa detection rate was 15.8%, and did not differ among the groups (P = 0.203). Regarding the percentage variation in PSA level, patients diagnosed with PCa tended to have their PSA level increased (22.4 vs -5.3%; P = 0.001). Indeed, a decrease of 20% in PSA was not predictive of a negative prostate biopsy (P = 0.41). • The area under the receiver operating characteristic curve for percentage PSA variation as a predictor of PCa was 0.660. • PSA levels tend to fall when repeated after 45 days, regardless of antibiotic use. • Despite being associated with the chance of PCa, no percentage PSA variation threshold value exhibits satisfactory discriminatory properties.

Associations of sexual dysfunction symptoms with PSA-detected localised and advanced prostate cancer: A case-control study nested within the UK population-based ProtecT (Prostate testing for cancer and Treatment) study

Background Sexual dysfunction might be symptomatic of cancer spreading beyond the prostate by local invasion, a mechanism of tumour progression associated with prognosis. Conversely, among men with raised prostate-specific antigen (PSA) levels, a negative association might be expected if sexual dysfunction was symptomatic of benign, rather than malignant, prostatic disease. Patients and methods Cases and controls were selected from among men recruited to 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 ⩾3.0 ng/ml were invited for biopsy. We investigated whether symptoms of sexual dysfunction, determined by self-completed questionnaire prior to biopsy, were associated with prostate cancer. Results Of the 8924 men who had a PSA level ⩾3.0 ng/ml (11% of the men who had a PSA test), 6585 underwent biopsy of whom 2813 and 421, respectively, were subsequently diagnosed with localised and advanced prostate cancer and 3351 had a negative biopsy result. No individual symptom of sexual dysfunction was associated with risk of prostate cancer. The symptom score was associated with advanced (odds ratio (OR) per one unit increase in score = 1.06; 1.00–1.12; P = 0.07) but not with localised (OR = 1.00; 0.97–1.02; P = 0.9) prostate cancer ( P = 0.05 for heterogeneity). Conclusions Our study provides weak evidence that sexual dysfunction may be associated with PSA-detected advanced, but not localised, prostate cancer among men with raised PSA levels.

Urological referral of asymptomatic men in general practice in England

The Prostate Cancer Risk Management Programme (PCRMP) launched in November 2002 provides guidelines for general practitioners (GPs) on age-specific prostate-specific antigen (PSA) cutoff levels in asymptomatic men. The impact of the PCRMP on GP referrals is unknown. This study investigates whether there was a change in the proportion of asymptomatic men with raised PSA levels (⩾3 ng ml−1) who were referred to urologists since the launch of the guidelines. Sixty-nine general practices in four areas of England and the main pathology laboratory in each area, which had participated in our previous research, were asked to provide data. Forty-eight practices (70%) provided retrospective data on urological referrals in men who had a PSA test taken in the periods 1 December 2001 to 31 May 2002 (pre-launch) and 1 December 2003 to 31 May 2004 (post-launch). Data on referrals were completed for 709 (79%) out of 898 and 1040 (90%) out of 1157 raised records pre- and post-launch, respectively. The percentage of men with raised PSA levels who were asymptomatic was similar in both time periods (19–20%) and the proportion referred to urologists according to the PCRMP guidelines did not increase significantly over time (24% pre-launch and 29% post-launch, P=0.42). The referral rate was lower than expected if the guidelines had been followed. The influence of the guidelines seems to have been low. At the time of data collection, 56% (112 out of 200) of GP partners reported that they were aware of receiving the PCRMP pack. To ensure future, effective implementation of guidelines requires evaluation.

Transrectal ultrasound‐guided biopsy of prostate voxels identified as suspicious of malignancy on three‐dimensional 1H MR spectroscopic imaging in patients with abnormal digital rectal examination or raised prostate specific antigen level of 4–10 ng/ml

Results of the evaluation of transrectal ultrasound (TRUS) guided needle biopsy of voxels identified as suspicious of malignancy on magnetic resonance spectroscopic imaging (MRSI) in a large cohort of men (n = 83) with abnormal digital rectal examination (DRE) [prostate specific antigen (PSA) 0-4 ng/ml] or PSA less than 10 ng/ml, are reported. Three-dimensional (1)H MRSI was carried out at 1.5 T using a pelvic-phased array coil in combination with an endorectal surface coil. Voxels were classified as suspicious of malignancy based on Cit/(Cho + Cr) metabolite ratio. TRUS-guided biopsy of suspicious voxels was performed using the z- and x-coordinates obtained from MR images and two to three cores were taken from the suspected site. A systematic sextant biopsy was also carried out. MRSI showed voxels suspicious of malignancy in 44 patients while biopsy revealed cancer in 11 patients (25%). Patients who were negative for malignancy on MRSI were also negative on biopsy. An overall sensitivity of 100%, specificity of 54%, negative predictive value of 100% and accuracy of 60% were obtained. The site of biopsy was confirmed (n = 20) as a hypo-intense area on repeat MRI while repeat MRSI revealed high choline and low citrate. The overall success rate of MRI-directed TRUS-guided biopsy of 25% was higher compared with a 9% success rate achieved without MR guidance in another group of 120 patients. Our results indicate that TRUS-guided biopsy of suspicious area identified as malignant from MRSI can be performed using the coordinates of the voxel derived from MR images. This increases the detection rate of prostate cancer in men with PSA level <10 ng/ml or abnormal DRE and also demonstrates the potential of MR in routine clinical practice.

Evidence of prostate cancer screening in a UK region.

To examine the pattern of use of prostate-specific antigen (PSA) testing in a UK region, where National Health Service policy does not recommend screening for prostate cancer. Data were collected on all PSA tests in Northern Ireland between 1990 and 1999. Annual rates of PSA testing were calculated by age, GP Practice and year. In all, 165 862 PSA tests were performed on 84 669 men, and over a third of men aged > or = 50 years had at least one PSA test. Men aged < 50 years accounted for 12.9% of first tests. The proportion of tests from primary care increased from 47.2% in 1993 to 67.0% in 1999. The mean age of men tested once decreased from 65.6 to 61.9 years (P trend < 0.001) and the proportion with an elevated PSA level also declined during the period. Repeat testing increased with PSA level (P < 0.001) but 29.4% of men with a PSA level of < or = 4 ng/mL also had repeat testing. Raised PSA values were more common from hospital than primary care (32.4% vs 20.6%, P < 0.001) and in older men. Test rates varied 100-fold across general practices, a finding not explained by sociodemographic factors, but one which reflects differential adherence to national guidelines, suggesting that general practitioners are key targets for attempting to rationalise the use of the PSA test. These findings suggest that PSA screening is taking place against evidence-based advice and has resulted in over 20 000 men being designated as having a raised PSA level, creating a need for further assessment.

Repeating the measurement of prostate-specific antigen in symptomatic men can avoid unnecessary prostatic biopsy.

To report the 2-year clinical and biochemical follow-up of symptomatic men who had a high prostate-specific-antigen (PSA) level, for whom our policy has been to avoid biopsy in those with a normal repeat PSA, as minimizing negative prostate biopsies is an important goal in managing men with a high PSA, where the decision for biopsy based on one high value may be inappropriate. In all, 101 men (median age 72 years, range 47-85) referred to a urology department over 1 year with a PSA level above the age-specific reference range (but < 50 ng/mL) had a repeat PSA measurement. Those with a normal PSA and a normal digital rectal examination (DRE) were not biopsied. Their follow-up included a symptom review, DRE and PSA measurements. Of the 101 men, 67% presented with LUTS, 11% with symptoms of urinary infection, 8% with haematuria and 9% for screening. In 35 patients the repeat PSA level was normal; in three of these 35 prostate cancer was diagnosed after biopsy because of an abnormal DRE, three were lost to follow-up and one died from unrelated causes. Thus 28 patients were available for review at 2 years. In 23 (82%) the PSA remained within the normal range. In 66 of the 101 men the repeat PSA was abnormal. Cancer was diagnosed in 28 and the remaining 36 with no cancer were managed by PSA review; 30 were reviewed at 2 years and in half of them the PSA level returned to normal. In symptomatic men referred with a raised PSA level and who have a normal DRE and normal repeat PSA, prostatic biopsy can be safely avoided.

Testosterone Treatment In Hypogonadal Men: Prostate-Specific Antigen Level And Risk Of Prostate Cancer

ObjectiveTo assess prostate-specific antigen (PSA) levels in hypogonadal men after testosterone replacement by three different methods and attempt to determine any possible relationship between hypogonadism and prostate cancer in this study population. MethodsA total of 90 consecutive men who had erectile dysfunction and were found to have hypogonadism were monitored with digital rectal examination (DRE) and measurement of PSA levels before and after testosterone replacement therapy. The patients were treated with one of three options: (1) testosterone enanthate by intramuscular injections, 200 or 300 mg every 2 or 3 weeks (N = 25); (2) testosterone nonscrotal patches, 5 mg daily (N = 16); or (3) clomiphene citrate, 50 mg orally three times a week, in patients with functional secondary hypogonadism (N = 49). Treatment was continued for 2 to 3 months, after which PSA levels were reassessed. Patients with suspicious results on DRE and increased PSA levels before or after treatment with testosterone underwent prostate biopsy. For statistical analysis, patients were categorized into two age-groups—40 to 60 years old and 61 to 80 years old. ResultsWith all methods of testosterone replacement, PSA levels increased in both age-groups. Endogenous testosterone elevation from clomiphene stimulation raised PSA levels the highest, and testosterone patches yielded the least PSA response. Ten men underwent biopsy of the prostate. In one patient, a nodule was found on DRE; the other nine men underwent biopsy because of suspicious PSA levels. Of these patients, two were found to have adenocarcinoma, and a third man who underwent rebiopsy was also found to have cancer. Therefore, 3 of the 90 patients (3.3%) had prostate cancer. ConclusionPSA levels increased in response to all types of testosterone replacement, regardless of whether the testosterone level was raised endogenously or exogenously. PSA levels are inappropriately low in hypogonadal men and may mask an underlying cancer. Determining PSA levels before and after testosterone treatment is recommended. Elevated PSA levels before or after testosterone therapy should prompt performance of a urologic evaluation for possible prostate biopsy. (Endocr Pract. 2000;6:132-138)

Free/total serum prostate-specific antigen ratio: how helpful is it in detecting prostate cancer?

To determine whether the use of free/total (f/t) serum prostate specific antigen (PSA) ratio would help reduce the number of prostate biopsies performed without compromising the detection of prostate cancer. in the setting of a transrectal ultrasonography (TRUS) clinic. The study included 93 consecutive patients referred to the clinic for TRUS and biopsy. Serum samples were assessed for total PSA and free PSA, and the f/t PSA ratio calculated: 70 biopsies were taken. Patients over the age of 70 years with TRUS findings consistent with benign prostatic hyperplasia and with PSA levels < 10 ng/mL were not biopsied. Tumour was detected in 23 patients; receiver operating characteristic curves showed no advantage for the f/t PSA ratio when compared with total PSA in detecting prostate cancer. If a f/t PSA ratio of < 0.15 had been used to determine the necessity for biopsy in the group with a total PSA of 4-10 ng/mL, then two-thirds of all tumours would have been undetected. The f/t PSA ratio had no advantage over total PSA in improving specificity at a given sensitivity for detecting prostate cancer. Therefore, it cannot be recommended as a means of decreasing unnecessary biopsies in patients with a raised PSA level and/or an abnormal digital rectal examination. This applied particularly to the group of patients with a total PSA of 4-10 ng/mL.

A review of radical prostatectomy from three centres in the UK: clinical presentation and outcome.

To examine critically the clinical presentation, pathological stage and outcome in patients selected for radical prostatectomy combining data from three centres where the operation has been carried out routinely for more than 5 years. Comparisons were made between impalpable tumours presenting at transurethral resection of the prostate (TURP) for clinically benign disease, tumours diagnosed at needle biopsy performed because the serum prostate-specific antigen (PSA) was elevated, and palpable, clinically localized cancer detected by digital rectal examination (DRE). Clinical and pathological findings recorded in the hospital notes of 183 patients who had undergone exploration for radical prostatectomy at St Bartholomew's Hospital, London, Southmead Hospital, Bristol, and the Royal Infirmary, Stirling, between 1987 and 1994 were transcribed onto a proforma and analysed. Patients were categorized by clinical stage and the relationships between clinical presentation, serum PSA level, pathological stage, tumour grade and outcome were examined. The pathological extent of clinically unsuspected cancer identified at TURP was highly variable. Well-differentiated tumours occupying < 5% of the TURP specimen were generally found to be less extensive at subsequent radical prostatectomy than either impalpable malignancy diagnosed by needle biopsy performed because PSA levels were raised or palpable tumours associated with a unilateral abnormality on DRE. Unsuspected tumours diagnosed at TURP that were less than well differentiated or occupied > 5% of the surgical specimen were more commonly associated with extra-prostatic invasion or metastatic disease than were tumours detected by raised PSA levels or an abnormal DRE. Serum PSA did not reliably predict either clinical stage or pathological extent, but no patient with nodal metastases had a PSA level of < 12 ng/mL. Similarly, pathological stage could not be predicted confidently from the whole-tumour grade ascertained after surgery. The extent of malignancy in patients referred because of lower urinary tract symptoms was not significantly different from that among patients referred specifically because the PSA level was raised or the DRE was abnormal. However, there was a trend for patients found to have cancer in specific screening programmes to have a malignancy that was less extensive and therefore more frequently confined to the gland than in those not identified by screening. Among patients with unsuspected malignancy diagnosed at TURP, those with well differentiated tumours in < 5% of the specimen had significantly less advanced disease than men found to have less differentiated or more extensive malignancy in the resected specimen. Impalpable cancer associated with a raised PSA level diagnosed by needle biopsy represented an intermediate group comparable to those with unilateral palpable malignancy. This suggests that needle biopsies may be worthwhile in some patients with an apparently benign prostate and raised PSA level with a view to identifying clinically significant but potentially curable cancer. Screening may detect less extensive tumours, but the natural history of these cancers is unknown and observed survival will be subject to lead-time and length bias when compared to symptomatic disease. Prospective randomized studies of both screening and treatment modalities, including surgery and radiotherapy, are required to define the impact of radical prostatectomy on disease-specific survival in men with early stage prostate cancer.

Screening for carcinoma of the prostate: a GP based study.

To examine the feasibility and acceptability of screening for cancer of the prostate by digital rectal examination (DRE), prostate specific antigen (PSA) determination and subsequent transrectal ultrasound (TRUS) in selected patients in a single general practice in Hertfordshire. A total of 568 of 856 men aged 55 to 70 accepted an invitation for a health check which included screening for prostate cancer. Of these, 80 individuals with either a raised PSA level or an abnormal DRE underwent TRUS. In 29 individuals biopsies were taken, 11 of which confirmed the presence of adenocarcinoma of the prostate giving an overall detected prevalence of 2%. Of the 11 tumours identified by screening, two were T1M0, four were T2M0, two were T3M0 and three were T3M1. To assess the acceptability of the screening exercise a postal questionnaire was sent to all 568 participants: 83% replied and 69% reported no concern. Of the 67 individuals who had undergone TRUS, 69% reported discomfort. A total of 448 (95%) of respondents declared that they would be prepared to undergo the screening exercise again. Screening for prostate cancer would seem to be technically feasible and generally acceptable. However, there is a considerable false positive rate in the PSA range 4 ng/ml to 10 ng/ml, particularly among men with clinical evidence of benign prostatic hyperplasia. To establish the true benefit of screening a large-scale prospective controlled study will be necessary.