Population-based screening for prostate cancer by measuring total serum prostate-specific antigen in Iran

OBJECTIVE: To report the results from an Iranian large population-based randomized study of screening using prostate-specific antigen (PSA) to detect prostate cancer. MATERIALS AND METHODS: A total of 3758 Iranian men older than 40 years were mass checked by PSA-based screening. Men with an abnormal digital rectal examination (DRE) and serum total PSA level of greater than 4 ng/mL, underwent transrectal ultrasonography (TRUS)-guided extended prostate biopsy. RESULTS: The PSA value (mean +/- standard deviation, SD) in all men without prostate cancer was 1.6 +/- 1.1 ng/mL and in those with cancer 18 +/- 44.8 ng/mL (P = 0.001). PSA values increased with age. In those aged 40-49, 50-59, 60-69 and > or = 70 years, the mean +/- SD PSA values were 1.3 +/- 0.7, 1.4 +/- 0.8, 1.8 +/- 1 and 2.2 +/- 1.6 ng/mL, respectively. Among the screened men, 323 (8.6%) had a serum PSA concentration greater than 4 ng/mL. Of patients who underwent prostate biopsy (230, 71.2%), 129 (positive predictive value, 56.1%) had prostate cancer. Additionally, nine cancers were detected among 16 patients with PSA of less than 4 ng/mL who had a doubtful DRE finding. The overall cancer detection rate was 3.6%; 1.4% at 40-49, 1.6% at 50-59, 4.2% at 60-69 and 12.9% at >/=70 years. Conventional systematic sextant biopsies, which accounted for six of the 10 cores in our biopsy scheme, detected 98 (71%) of the cancers. CONCLUSIONS: The Iranian male population develops prostate cancer quite commonly if their serum PSA levels are greater than 4.0 ng/mL. In this study, 65.9% of the detected cancers were clinically significant. The conventional systematic sextant technique may be inappropriate for detection of all prostate cancers. The results need to be confirmed in other randomized trials.     

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.     

Are prostatic biopsies necessary in men aged > or =80 years?

OBJECTIVE: To examine whether prostatic biopsies are necessary in all men aged > or =80 years, as men found to have prostate cancer are frequently treated with a 'watch and wait' policy or with hormonal withdrawal alone, and biopsies are associated with a small but significant complication rate. PATIENTS AND METHODS: The findings on a digital rectal examination (DRE), the prostate-specific antigen (PSA) level, the biopsy and staging bone scan results for all men aged > or = 80 years who had prostatic biopsies over a 3-year period were reviewed, together with those in a group of men aged <80 years for comparison. All biopsy samples had been examined in one of three histopathology units, and 33 consultant urological surgeons contributed. RESULTS: In all, 210 biopsies from 205 men aged > or = 80 years were identified, of whom 163 (79%) had biopsy-confirmed prostate cancer. All 29 men with a PSA level of > or = 100 ng/mL, 98% of 47 with > or = 50 ng/mL, 97% of 76 with > or = 30 ng/mL and 92% of 101 with > or = 20 ng/mL had biopsy cores containing cancer; 63% of men with a PSA level of <20 ng/mL had cancer on biopsy. In men with cancer and a PSA level of > or = 30 ng/mL, 92% had Gleason grade > or = 7 and 93% were treated with hormonal withdrawal alone. In all men with cancer the DRE was abnormal in 91%, the mean number of positive cores was 59% and the bone scan was positive in 18%. The DRE was abnormal in 77% of men with benign biopsies. CONCLUSIONS: In men aged > or = 80 years with a PSA level of > or = 30 ng/mL, at least 97% had prostate cancer, >90% of whom had high-grade disease, and nearly all with cancer received active pharmacological treatment. In the vast majority of these men prostate biopsies did not alter their cancer management. The value of prostatic biopsy in this age group, with a PSA level of > or = 30 ng/mL, is questionable.     

Predicting the extent of prostate cancer using the combination of systematic biopsy and serum prostate-specific antigen in Japanese men

OBJECTIVE: To determine the utility of systematic biopsy alone or combined with an assay of serum prostate-specific antigen (PSA) level to predict the extent of prostate cancer in Japanese men. PATIENTS AND METHODS: Thirty-two patients who were diagnosed as having clinically organ-confined prostate cancer and who underwent prostatectomy were evaluated retrospectively for the results of systematic biopsy (percentage of positive biopsy cores and cancer location), serum PSA and the pathological stage of whole-mount sections of the prostatectomy specimens. RESULTS: The incidence of extraprostatic disease (pT3N0M0 or N+) in patients with >/= 8 ng/mL of serum PSA and cancer in bilateral lobes was significantly higher than in those with <8 ng/mL PSA and cancer in one lobe (83% vs 30%, P=0.020). In those with more than half the biopsy cores positive, extraprostatic disease was significantly more common than in those with less than half positive (93% vs 44%, P=0.0075); moreover, in patients with more than half the cores positive and >/= 8 ng/mL serum PSA, it was significantly more common than in those with less than half positive and <8 ng/mL of serum PSA (93% vs 27%, P=0.0021). However, the incidence of extraprostatic disease predicted by three variables (cancer location, percentage positive biopsy cores and serum PSA) was not significantly better than that predicted by two variables (percentage positive cores and serum PSA). CONCLUSIONS: The combination of systematic biopsy and serum PSA may be useful in predicting extraprostatic cancer. Patients with >/= 8 ng/mL serum PSA and more than half the biopsy cores positive could avoid a prostatectomy because there is a high probability that they have extraprostatic disease.     

Elevated serum prostate specific antigen levels in conjunction with an initial prostatic biopsy negative for carcinoma: who should undergo a repeat biopsy?

OBJECTIVE: To determine the outcome of repeated prostatic biopsies in men attending with suspected prostate cancer but an initial negative biopsy. PATIENTS AND METHODS: Patients who had undergone two or more transrectal ultrasonography (TRUS)-guided prostate biopsies were identified from the Hospital Information Support System database. Indications for TRUS were a raised prostate-specific antigen (PSA) level (>4.0 ng/mL), with or without an abnormal digital rectal examination (DRE). Sextant prostate biopsies plus biopsies of any suspicious hypoechoic area or area of DRE abnormality were obtained for histology. Forty-eight patients underwent repeat TRUS-guided prostatic biopsies (mean age 67.5, sd 7. 25, range 53-82 years). RESULTS: The mean (sd, median, range) PSA level was 16.9 (13.5, 11.6, 5.2-61.8) ng/mL. Fifteen patients (31%) had carcinoma on repeat biopsy, 11 after the second and four after a third biopsy. The positive repeat biopsy rate was 24% where the PSA level was 4.0-9.9 ng/mL, 33% if the level was 10.0-19.9 ng/mL and 39% if it was >/=20.0 ng/mL. There was no significant difference in age or initial PSA concentration between those men with positive and those with negative repeat biopsies. However, patients with cancer had significantly higher PSA levels before repeat biopsy than at first biopsy (P=0.0043) and had greater PSA velocities than had patients with no diagnosis of cancer (P=0.0067). CONCLUSION: Where sufficient clinical suspicion exists, despite an initial negative biopsy, repeat TRUS-guided prostate biopsies should be carried out to exclude carcinoma of the prostate.     

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.     

Neoadjuvant Hormonal Therapy Improves the Outcomes of Patients Undergoing Radioactive Seed Implantation for Localized Prostate Cancer

Neoadjuvant hormonal therapy (NHT) has been extensively studied in patients undergoing radical prostatectomy and external-beam irradiation for prostate cancer. While there are a few reports in the literature on its use in men undergoing brachytherapy, little information exists about its beneficial effects in such patients. In this report, we describe the effects of NHT on prostate volume (PV) prior to seed implantation and on the prostate specific antigen (PSA) and postimplant biopsy outcomes of patients who presented with high-risk features. Hormone therapy (leuprolide and flutamide 750 mg/day) was given to 145 patients for 3 months prior to and for 3 months after permanent iodine-125 (160 Gy) or palladium-103 (115 Gy) seed implantation. Of these, 28 (19%) received NHT because of a preimplant PV >50 cc, and 117 patients received NHT because they had a PSA >10 ng/mL, Gleason score >/=7, or clinical stage >/=T(2b). All patients underwent implantation using the real-time intraoperative method, and no patients received external-beam irradiation. Of the 145 patients treated, 67 (46%) had a PSA >10 ng/mL (range 1.9-57 ng/mL; mean 12.2 ng/mL), 50 (35%) had Gleason score >/=7, and 80 (55%) had stage >/=T(2b) disease. Prostate volume was measured in 106 patients prior to NHT and 3 months later immediately prior to the seed implant. The mean PV was 50.4 cc (range 17-150 cc), whereas the mean PV after NHT was 31 cc (range 11.7-73.7 cc). The mean PV reduction was 35% (range 2%-62%). Volume reduction was compared in those patients who presented with a PV <40 cc (N = 51) and those with a PV >/=40 cc (N = 56). The mean reduction for the smaller glands was 29% (range 2%-54%) compared with 41% (range 7%-62%) for the larger glands (P < 0.05). Patients were followed for a minimum of 1 year (range 1.0-6.4; mean 2.2 years). The 4-year actuarial rate of freedom from PSA failure (PSA >1.0 ng/mL with two consecutive elevations) was 85%. There was no difference in rates of freedom from PSA failure for those with initial Gleason 2-4 (96%), 5-6 (78%), 7 (80%), or 8-9 (83%; P = 0.5). Control rates were 85% for patients with PSA 20 ng/mL (P = 0.8). There was a trend to decreased control rates with higher-stage disease (98% for T(1)-T(2a) v 68% for T(2c)), but these differences were likewise not significant (P = 0.12). The control rates for the 28 low-risk patients with enlarged prostate glands were compared with those of the 117 with high-risk features and were not different (100% v 82%; P = 0.1). There were 62 patients who agreed to eight-core prostate biopsies 2 years after implantation, and 60 (97%) were negative for tumor. This trial shows that NHT can reduce PV an average of 35% prior to seed implantation with the greatest reduction found in patients with larger prostates (41%). Hormonal therapy also appears to improve biochemical (PSA) control and local control (prostate biopsy) in patients with high-risk disease, yielding results similar to those in men with low-risk prostate cancer.     

Problems with prostate specific antigen screening for prostate cancer in the primary healthcare setting in South Africa

OBJECTIVES: To assess the feasibility of detecting early-stage prostate cancer in the primary healthcare setting, and to investigate whether there is a higher incidence of prostate cancer in Black African men. PATIENTS AND METHODS: The study was a collaboration with registrars in the authors' institutions and primary healthcare centres serving mainly a Black African or mixed ancestry (Coloured) population in the semi-urban Cape Town metropolitan area of South Africa. Men aged 50-70 years attending the clinics were counselled about prostate cancer and invited to have a digital rectal examination (DRE), serum prostate-specific antigen (PSA) assay and transrectal ultrasonography-guided sextant prostate biopsy if the DRE was clinically suspicious of malignancy or the serum PSA was > or = 4.0 ng/mL. An American Urological Association Symptom Index (AUA-SI) was obtained, and urine analysed using dipsticks. RESULTS: From May 2000 to November 2001, 660 men were assessed (mean age 59.4 years, range 30-82); 60.6% were Black African, 37.3% mixed (Coloured), 1.8% White (Caucasian) and 0.2% Asian (Indian). The mean (range) AUA-SI was 5.98 (0-35) in the whole group; the DRE was recorded as clinically suspicious of malignancy in 3.2%. The mean PSA was 20.39 (0.04-10 000) ng/mL in the whole group, but when two outliers (1865 and 10 000 ng/mL) were disregarded, it was 2.4 ng/mL. In Black patients the mean PSA was 31.8 (0.04-10 000) ng/mL, and without the outliers, 2.1 ng/mL; in Coloured patients it was 2.94 (0.05-50) ng/mL. The PSA was > or = 4.0 ng/mL in 9.6% of the whole group, in 7.8% of Black and in 13% of Coloured patients. Prostate biopsies were taken in 21 patients (3.2% of the whole group and a third of those with a PSA of > or = 4.0 ng/mL); in Black patients, biopsies were taken in 1.5% and 19.4%, respectively, and in Coloured patients in 6.1% and 46.9%, respectively. The prostate biopsy showed cancer in 43% of the whole group, in a third of Black and in 47% of Coloured patients; prostate cancer was detected in 1.4%, 0.5% and 2.8%, respectively. CONCLUSIONS: That prostate biopsies were obtained in only 19% of Black and in only 47% of Coloured men with a serum PSA of > or = 4.0 ng/mL is of concern. This indicates that there is a significant problem in getting men with an elevated serum PSA level to undergo a prostate biopsy in the primary healthcare setting in South Africa.     

Early diagnosis of prostate cancer in the Western Cape.

BACKGROUND: Early stage prostate cancer does not cause symptoms, and even metastatic disease may exist for years without causing symptoms or signs. Whereas early stage prostate cancer can be cured with radical prostatectomy or radiotherapy, the prognosis of patients with locally advanced or metastatic cancer is significantly poorer. OBJECTIVES: In view of the high incidence of advanced and therefore incurable prostate cancer seen at the oncology clinic of the Department of Urology, Tygerberg Hospital, we started a prostate clinic with the aim of detecting early stage prostate cancer which is potentially curable. A secondary objective was to investigate the question whether there is a higher incidence of prostate cancer among black African men. PATIENTS AND METHODS: Men aged 50-70 years were invited by means of media communications (newspaper and radio) to attend our prostate clinic for a free physical examination, including a digital rectal examination (DRE) and serum prostate specific antigen (PSA) assay. If the DRE was clinically suspicious of malignancy and/or the serum PSA was > 4 ng/ml, the patient was appropriately counselled and referred for transrectal ultrasound (TRUS)-guided sextant prostate biopsy. RESULTS: In the period June 1997-September 1999 a total of 1,056 men attended the prostate clinic. Biopsies were indicated in 160 cases, and were obtained in 114 (71.3%, i.e. 10.8% of the entire cohort). Prostate cancer was detected on first biopsy in 3.5% of the entire group of men (in 35.9% of those with a clinically abnormal DRE, in 41.3% of those with a serum PSA > 4 ng/ml and in 88.6% of those with an abnormal DRE and serum PSA > 4 ng/ml. In the 37 men with prostate cancer, the clinical tumour stage was T1-2 in 83.8% and T3-4 in 16.2%. In the group of patients with clinical stage T1-2 tumours, the treatment was watchful waiting in 62.5% of cases, radiotherapy in 20.8% and radical prostatectomy in 16.7%. Analysis of the data according to race showed that in the group of 47 black men there was a higher percentage of clinically abnormal DRE, PSA > 4.0 ng/ml and biopsies showing malignancy, and a higher overall prostate cancer detection rate (8.5%). CONCLUSIONS: Our prostate cancer detection rate of 3.5% is slightly lower than that reported in larger studies (4.7%), which may be due to the fact that prostate biopsy was performed in only 71% of those who had an indication for biopsy. In the men diagnosed with clinically localised prostate cancer, potentially curative treatment was given in only 37.5% of cases. This compares unfavourably with the historical cohort of men seen at our oncology clinic, where 53% received potentially curative treatment, and a large European study where potentially curative treatment was given in 89% of cases. Our finding that black men had a higher percentage of clinically abnormal DRE, PSA > 4.0 ng/ml and biopsies showing malignancy and a higher overall detection rate of prostate cancer should be interpreted with caution, since black men comprised only 4.5% of our overall study cohort.     

The role of the digital rectal examination in subsequent screening visits in the European randomized study of screening for prostate cancer (ERSPC), Rotterdam

BACKGROUND: The value of digital rectal examination (DRE) as a screening test for prostate cancer (PC) is controversial in the current prostate-specific antigen (PSA) era. OBJECTIVES: To determine (1) the additional value of a suspicious DRE for the detection of PC in men with an elevated PSA level in subsequent screenings and (2) the tumour characteristics of PCs detected in men with a suspicious DRE. DESIGN, SETTING, PARTICIPANTS: Within the screening study, from 1997-2006 men aged 55-75 years were invited for an every 4-yr PSA determination. A PSA level >/=3.0ng/ml prompted a DRE and a transrectal ultrasound (TRUS)-guided, lateralized sextant biopsy. Throughout the three screenings of the ERSPC, Rotterdam, 5040 biopsy sessions were evaluated. MEASUREMENTS: We determined the positive predictive values (PPVs) of a suspicious DRE and normal DRE, which entailed, respectively, the proportion of PCs detected in men with a suspicious DRE or normal DRE divided by, respectively, all biopsied men with a suspicious DRE or normal DRE. RESULTS AND LIMITATIONS: At initial screening, the PPV of a suspicious DRE, in conjunction with an elevated PSA level, to detect PC was 48.6% compared to 22.4% for men with a normal DRE. Both PPVs decreased in consecutive screens: respectively, 29.9% versus 17.1% (screen 2) and 21.2% versus 18.2% (screen 3). Respectively, 71.0% (p<0.001), 68.8% (p<0.001), and 85.7% (p=0.002) of all PCs with a Gleason score >7 were detected in men with a suspicious DRE at screens 1, 2, and 3. A limitation is that only biopsied men were evaluated. CONCLUSIONS: At initial and subsequent screenings, the chance of having cancer at biopsy was higher in men with a suspicious DRE compared to men with a normal DRE (to a lesser extent in subsequent screenings), and the combination of a PSA level >/=3.0ng/ml with a suspicious DRE resulted in detecting significantly more PCs with Gleason score >7. DRE may be useful in more selective screening procedures to decrease unnecessary biopsies and overdiagnosis.     

Prevalence of undiagnosed prostate cancer in men with erectile dysfunction

OBJECTIVE: To explore the prevalence of prostate cancer in men presenting with erectile dysfunction (ED). PATIENTS AND METHODS: In a prospective study, 127 men with ED of at least 6 months duration underwent screening for prostate cancer using prostate specific antigen (PSA) and a digital rectal examination (DRE). Men with a high PSA level (> 4 ng/mL) had sextant biopsies taken under sedoanalgesia. The serum testosterone level was measured in all the men. RESULTS: Twenty-six men were aged < 50 years and all had a normal PSA level; of 101 men aged > 50 years, 20 had an abnormal PSA. The detection rate for prostate cancer using PSA and DRE was 5%, which was not significantly higher than in the general population. All the detected cancers were clinically significant (> T2a, Gleason grade > 4). Two of the five men diagnosed with prostate cancer were Afro-Caribbean. Of the 127 men, 31% had a low serum testosterone level, but there was no association between testosterone and PSA levels. CONCLUSIONS: Prostate cancer is no more common in men with ED than in the normal male population. Therefore, routine screening for prostate cancer in men with ED is not indicated.     

Diagnostic value of percent free prostate-specific antigen: retrospective analysis of a population-based screening study with emphasis on men with PSA levels less than 3.0 ng/mL

OBJECTIVES: To retrospectively investigate the use of percent free prostate-specific antigen (PSA) compared with total PSA in serum as predictor of prostate cancer in men selected randomly from the general population who underwent biopsy on the basis of abnormal findings on digital rectal examination (DRE) or transrectal ultrasound (TRUS) and/or serum PSA levels greater than 10 ng/mL. METHODS: A single intervention, population-based screening study was undertaken in 1988 and 1989. Of the 2400 men aged 55 to 70 years invited to participate, 1782 men responded and were examined with DRE, TRUS, and PSA testing (Tandem-Hybritech). In 1995, frozen serum samples from 1748 men were analyzed for percent free PSA (Prostatus, Wallac OY). Five-year follow-up data on new cancers in the screened population were obtained from the Swedish Cancer Registry (SCR). RESULTS: Of the 1748 men, 367 underwent TRUS-guided biopsies because of abnormal findings on either DRE or TRUS or serum PSA levels of greater than 10 ng/mL. This resulted in the diagnosis of 64 cases of prostate cancer (3.7%). PSA levels of 3.0 ng/mL or greater were found in 55 (86%) of 64 cancer cases and in 399 (24%) of the 1684 benign cases. Among the 1294 men with PSA less than 3.0 ng/mL, 9 prostate cancers were diagnosed (14% of all prostate cancers). All 9 patients with cancer and with PSA less than 3.0 ng/mL had a percent free PSA of 18% or less. In the group of 1109 patients with PSA less than 3.0 ng/mL and a percent free PSA greater than 18%, 159 biopsies were performed because of abnormal DRE or TRUS. However, no prostate cancer was diagnosed in this category of patients. Five years after the screening intervention, 7 more cases of prostate cancer were clinically diagnosed in the screened population according to the SCR. CONCLUSIONS: The combination of PSA levels less than 3.0 ng/mL and percent free PSA greater than 18% defines a large part of the population at a very low risk of cancer of the prostate both at the time of screening and during the following 5 years. Men in this group may be spared DRE, and longer screening intervals may be considered. However, the risk of having prostate cancer is not negligible in men with PSA less than 3.0 ng/mL and percent free PSA of 18% or less. The results of this study indicate that biopsy should be recommended to men fulfilling these criteria, although these results should be confirmed in larger prospective studies because of the limited number of patients with prostate cancer in the present series.     

Diagnostic value of serum prostate-specific antigen in hemodialysis patients

BACKGROUND: The value of serum prostate-specific antigen (PSA) screening was examined to detect prostate cancer in men receiving hemodialysis. METHODS: Forty-one male patients age 60-95 (median age, 70 years) receiving hemodialysis were investigated for PSA levels. We set the cut-off point at 4 ng/mL (the usual reference range). Digital rectal examination (DRE) and transrectal ultrasonography (TRUS) of the prostate were performed in patients whose PSA was more than 4 ng/mL and/or who expected further examination of the prostate. When prostate cancer was suspected, biopsy of the prostate was performed. In patients with prostate cancer, magnetic resonance imaging, computed tomography and bone scintigraphy were performed to diagnose the clinical stage. RESULTS: The mean serum level of PSA was 2.10 +/- 0.49 ng/mL. In this screening study, four of 41 men required further examinations for prostate cancer. Two of four refused further examinations. The other two were diagnosed with prostate cancer. The incidence of prostate cancer was at least 5% in our hemodialysis patients. One man, whose clinical stage was T2aN0M0, was treated with radical retropubic prostatectomy. Another man, whose clinical stage was T2bN0M0, was treated with luteinizing hormone-releasing hormone analogue. CONCLUSION: In our preliminary study, prostate cancer screening with PSA was useful for the early detection of prostate cancer in hemodialysis patients. If possible, DRE and TRUS should be performed in conjunction with PSA tests.     

Clinicopathological Features of Prostate Cancer Detected by Transrectal Ultrasonography-Guided Systematic Six-Sextant Biopsy

Background :
The objectives of this study were to compare the efficacy of 3 modalities (prostate-specific antigen (PSA) assay, digital rectal examination (DRE), and transrectal ultrasonography (TRUS)) in detecting prostate cancer which was pathologically confirmed by TRUS-guided systematic six-sextant biopsy, and to investigate the relationship between the number of positive cores and several clinicopathological parameters.
Methods :
Between 1 992 and 1994, 297 males (155 from a mass screening program and 142 identified as outpatients) with a mean age of 71 years, underwent examinations including PSA determination, DRE, TRUS and systematic six-sextant biopsy, and/or additional directed biopsy.
Results :
Prostate cancer was detected in 93 men. The sensitivity level of the PSA assay was significantly higher (85%) than that of either DRE or TRUS. Patients with an abnormal DRE or TRUS, elevated PSA levels, and those in the T3-T4 category or with moderate to poorly-differentiated adenocarcinomas had more positive biopsy cores (P< 0.05). Also, the relationships of both the number of positive biopsy cores and tumor grade to bone metastasis were significant (P < 0.01). Of 209 hypoechoic areas identified by transrectal ultrasonography, 42% were cancerous, and of 427 isoechoic areas, 1 2% were cancerous. The percentage of positive biopsy cores with hypoechoic areas was 86% in the subjects with a PSA > 10 ng/mL, but low (9%) in subjects with a PSA < 4 ng/mL, and the percentage of negative biopsy cores with a normal TRUS was high (98%) in subjects with a PSA of < 4 ng/mL, but lower (67%) in subjects with a PSA > 10 ng/mL.
Conclusion :
The serum PSA assay was more useful than either DRE or TRUS in detecting prostate cancer. The percentage of bone metastasis increased concomitant with the number of positive biopsy cores, and the positive biopsy rate of hypoechoic areas positively correlated with the PSA level.     

Prostate-specific antigen changes in hypogonadal men treated with testosterone replacement

Testosterone supplementation is commonly used as a treatment for hypogonadal men with or without erectile dysfunction. The effect of parenteral testosterone replacement therapy on the development or growth of prostate cancer is unclear. We assessed the effect of this treatment on serum prostate-specific antigen (PSA) levels and risk of prostate cancer in hypogonadal men with erectile dysfunction. Criteria for inclusion were a normal pre-treatment PSA (<4.0 ng/mL) in conjunction with a normal digital rectal examination (DRE) or a negative pretreatment prostate biopsy for men with either an abnormal DRE or an elevated PSA. Patients received intramuscular injections every 2 to 4 weeks, allowing for dose titration. In this retrospective analysis, 54 hypogonadal men with erectile dysfunction were included, with a mean age of 60.4 years (range 42.0-76.0) and a mean follow-up of 30.2 months (range 2.0-82.0) on testosterone therapy. Mean pretreatment total testosterone level was 1.89 ng/mL (range 0.2-2.92), which increased during treatment to a mean of 9.74 ng/mL (range 1.50-26.30, P <.001). Mean pretreatment PSA was 1.86 ng/mL (median 1.01 ng/mL, range 0.0-15.80), which increased to a mean PSA level of 2.82 ng/mL (median 1.56 ng/mL, range 0.0-32.36, P <.01) with testosterone treatment. Of the 54 men included in this study, 6 (11.1%) required prostate biopsy while on testosterone therapy because of a rise in serum PSA above 4.0 ng/mL. One patient (1.9%) was diagnosed with prostate cancer. In conclusion, testosterone replacement therapy in men with erectile dysfunction and hypogonadism is associated with a minor PSA elevation, but there does not appear to be a short-term increase in risk for the development of prostate cancer.     

Prostate cancer screening in the Prostate,Lung, Colorectal and Ovarian cancer screening trial: update on findings from the initial four rounds of screening in a randomized trial

OBJECTIVE

To describe the results of the first four rounds (T0‐T3) of prostate cancer screening in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial (designed to determine the value of screening in the four cancers), that for prostate cancer is evaluating whether annual screening with prostate‐specific antigen (PSA) and a digital rectal examination (DRE) reduces prostate cancer‐specific mortality.

SUBJECTS AND METHODS

In all, 38 349 men aged 55–74 years were randomized to undergo annual screening with PSA (abnormal >4.0 ng/mL) and a DRE. The follow‐up of abnormal screening results was at the discretion of subjects’ physicians. PLCO staff obtained records related to diagnostic follow‐up of positive screen results.

RESULTS

Compliance with screening decreased slightly from 89% at baseline to 85% at T3. Both PSA positivity rates (range 7.7–8.8% at T0‐T3) and DRE positivity rates (range 6.8–7.6% at T0‐T3) were relatively constant over time. The positive predictive value (PPV) of a PSA level of >4.0 ng/mL decreased from 17.9% at T0 to 10.4–12.3% at T1‐T3; the PPV for DRE (in the absence of a positive PSA test) was constant over time (2.9–3.6%). Cancer was diagnosed in 1902 men (4.9%). Screen‐detected cancers at T0 (549) were more likely to be clinical stage III/IV (5.8%) and to have a Gleason score of 7–10 (34%) than screen‐detected cancers at T1‐T3 (1.5–4.2% stage III/IV and 24–27% Gleason score 7–10 among 1054 cases).

CONCLUSION

The present findings on serial prostate screening are similar to those reported from other multi‐round screening studies. Determining the effect of PSA screening on prostate cancer mortality awaits further follow‐up.     

Age, prostate-specific antigen, and digital rectal examination as determinants of the probability of having prostate cancer

Objectives. The decision to perform prostate biopsy has traditionally been based on an abnormal prostate-specific antigen (PSA) level or abnormal digital rectal examination (DRE) findings. For example, a 60-year-old man with a benign DRE and PSA level of 4.1 ng/mL would be counseled for biopsy, and the same man with a PSA level of 3.9 ng/mL might be counseled against biopsy. However, the difference in these PSA levels and in the likelihood of these two men having prostate cancer is not significant. We constructed a probability nomogram for the likelihood of detecting prostate cancer, thus aiding in the decision of whether to perform a prostate biopsy.Methods. Using multivariate logistic regression analysis and data from 2054 men (mean age 64 years) participating in the Tyrol Screening Project between January 9, 1993 and January 9, 1997, patient age, PSA level, and DRE findings were analyzed for their ability to determine the likelihood of finding prostate cancer on transrectal ultrasound-guided biopsy.Results. DRE was suspicious in 278 men (13.5%). Overall, 498 (24.5%) of 2054 men biopsied had prostate cancer. The probability of discovering cancer on biopsy was calculated using patient age, DRE findings, and PSA level.Conclusions. DRE status had a large influence on the likelihood of positive biopsy across all PSA and age ranges. A combination of PSA, DRE result, and age better defined the probability of a positive biopsy than any factor alone. Using this nomogram, the decision to proceed with or defer prostate biopsy can be based on an actual probability of discovering prostate cancer rather than a single PSA-based cutpoint. These data may aid physicians and patients in decision-making.     

Serum testosterone levels in African-American and white men undergoing prostate biopsy

Objectives. Because androgen levels are known to influence prostate growth, we performed a prospective analysis of serum testosterone levels in all African-American and white men who underwent transrectal ultrasound-guided prostate biopsies to evaluate an abnormal digital rectal examination (DRE) and/or serum prostate-specific antigen (PSA) level greater than 4 ng/mL.Methods. From June 1996 through July 1998, we evaluated 453 men (189 African-American and 264 white men) who underwent prostate needle biopsy because of an abnormal DRE or serum PSA greater than 4 ng/mL, or both. All men had morning serum testosterone levels determined just before undergoing prostate needle biopsy. Serum testosterone levels were compared on the basis of the prostate biopsy result (positive or negative for prostate cancer) and by race.Results. A total of 453 men underwent prostate biopsy and had morning serum testosterone levels available for comparison. Of the 264 white men who underwent biopsy, 88 (33%) were found to have prostate cancer compared with 67 (35%) of 189 African-American men who underwent biopsy. In the white men without cancer, the mean serum testosterone level was 380.19 ng/dL; those with prostate cancer had a mean serum testosterone level of 419.52 ng/dL. The mean serum testosterone level in African-American men without cancer was 424.30 ng/dL; it was 386.55 ng/dL in those with prostate cancer. There was no statistical difference in serum testosterone levels based on biopsy result or race.Conclusions. Although several studies have suggested that African-American men have higher serum testosterone levels than white men, these differences were noted only in men 40 years of age or younger. As was noted in our study, after age 40, African-American and white men have comparable serum testosterone levels. In addition, although prostate growth is androgen dependent, we found no difference in serum testosterone levels in men with and without prostate cancer.     

Would prostate cancer detected by screening with prostate-specific antigen develop into clinical cancer if left undiagnosed? A comparison of two population-based studies in Sweden

OBJECTIVE: To assess the risk of over-diagnosing and over-treating prostate cancer if population-based screening with serum prostate-specific antigen (PSA) is instituted. PATIENTS AND METHODS: From a serum bank stored in 1980, PSA was analysed in 658 men with no previously known prostate cancer from a well-defined cohort from G?teborg, Sweden (men born in 1913); the incidence of clinical prostate cancer was registered until 1995. From the same area, and with the same selection criteria, another cohort of 710 men born in 1930-31, who in 1995 accepted an invitation for PSA screening, was also analysed. RESULTS: Of men born in 1913, 18 (2.7%) had died from prostate cancer and the cumulative probability of being diagnosed with clinical prostate cancer was 11.1% (5.0% in those with a PSA level of < 3 ng/mL vs 32.9% in those with a PSA level of > 3 ng/mL, P < 0.01). The mean lead-time from increased PSA (> 3 ng/mL) to clinical diagnosis was 7 years. The prostate cancer detection rate in men born in 1930-31 was 4.4% (22% among those with increased PSA levels) and 30 of 31 detected cancers were clinically localized. CONCLUSIONS: Screening and sextant biopsies resulted in a lower detection rate (22%) than the cumulative risk of having clinical prostate cancer (33%) in men with increased PSA levels, indicating that under-diagnosis rather than over-diagnosis is the case at least with 'one-time' screening. Even if the stage distribution in screening-detected cancers seems promising (and thus may result in reduced mortality) it is notable that screening 67-year-old men will result in treatment a mean of 7 years before clinical symptoms occur and only one in four men anticipated to develop prostate cancer will die from the disease within 15 years. Large randomized screening trials seem mandatory to further explore the benefits and hazards of PSA screening.     

Tissue-resonance interaction method for the noninvasive diagnosis of prostate cancer: analysis of a multicentre clinical evaluation

OBJECTIVE: To determine, in a multicentre prospective study, the accuracy of the tissue-resonance interaction method (TRIMprob, new technology developed for the noninvasive analysis of electromagnetic anisotropy in biological tissues) in the diagnosis of prostate cancer. PATIENTS AND METHODS: Two hundred patients (mean age 67.4 years) scheduled to have prostatic biopsies (because of a prostate-specific, PSA, antigen level of >/=4 ng/mL or a suspicious digital rectal examination, DRE) were preliminarily examined while unaware of their clinical details using TRIMprob in five different centres. The final diagnosis obtained with TRIMprob was compared with the final histological diagnosis after extended biopsies. RESULTS: Of the 188 evaluable patients (mean PSA level 9.3 ng/mL, sd 8.8; mean prostate volume 62.0 mL, sd 32.4), 61 (32.4%) had a positive biopsy for adenocarcinoma of the prostate. The overall sensitivity, specificity, positive predictive value, negative predictive value (NPV) and accuracy of TRIMprob were 80%, 51%, 44%, 84% and 60%, respectively. The prostate cancer detection rate after biopsy was significantly higher in patients with a positive examination (49/111, 44%) than in patients with a negative TRIMprob (12/77, 15%; P < 0.001). When TRIMprob results were combined with DRE findings the sensitivity and NPV both increased to 92%. CONCLUSION: TRIMprob seems to be a useful tool in the diagnosis of prostate cancer and can increase the accuracy of PSA or DRE results. The high NPV suggests that this new technology might be useful to reduce the indications for prostatic biopsy or repeated series of biopsies in patients suspected of having prostate cancer.