SERUM AND SEMEN PROSTATE SPECIFIC ANTIGEN CONCENTRATIONS ARE DIFFERENT IN YOUNG SPINAL CORD INJURED MEN COMPARED TO NORMAL CONTROLS

PURPOSE: Recent investigations have indicated that factors within the seminal plasma may contribute to the condition of low sperm motility in men with spinal cord injury. To determine whether the prostate gland functions normally in these men we chose prostate specific antigen (PSA) as a marker of prostatic function, and compared serum and semen concentrations in spinal cord injured and healthy noninjured men. MATERIALS AND METHODS: The study included 21 spinal cord injured men (mean age 33.3+/-1.2 years) and 22 noninjured normal men (mean age 30.3+/-1.5 years). Blood was obtained from subjects following at least 24 hours of abstinence from ejaculation and serum PSA was determined by modified enzyme immunoassay. Antegrade ejaculates from all subjects were frozen to -80 C, exactly 15 minutes after collection. Seminal plasma PSA was determined using Hybritech Tandem MP assay. RESULTS: Mean serum PSA concentration was 1.20+/-0.19 ng./ml. in spinal cord injured and 0.69+/-0.07 ng./ml. in noninjured men (p<0.02). Mean seminal plasma PSA concentration was 0.59+/-0.11 mg./ml. in spinal cord injured and 1.29+/-0.15 mg./ml. in noninjured men (p<0.001). CONCLUSIONS: Our findings of elevated serum and decreased seminal plasma PSA concentrations indicate that prostatic secretory dysfunction is present in men with spinal cord injury.     

The accuracy of the increased prostate specific antigen level (greater than or equal to 20 ng./ml.) in predicting prostate cancer: is biopsy always required?

PURPOSE: Urologists are often referred patients who initially present with an extremely high serum prostate specific antigen (PSA) level. Despite a presumptive diagnosis of prostate cancer, many of these men undergo biopsy to obtain a tissue diagnosis before treatment with androgen ablative therapy. We examined a data base of men undergoing prostate biopsy to determine the accuracy of high PSA levels (greater than or equal to 20 ng./ml.) in predicting prostate cancer. MATERIALS AND METHODS: We reviewed the records of 1,250 consecutive patients undergoing transrectal ultrasound guided prostate biopsy at 1 institution. From this data base we identified all patients with PSA greater than or equal to 20 ng./ml. at the time of prostate biopsy. The accuracy of PSA in predicting cancer was determined by calculating positive predictive values for PSA ranges and PSA cutoffs. RESULTS: We identified 187 men (15%) presenting with PSA greater than or equal to 20 ng./ml. Of these 187 men 157 (84.0%) were diagnosed with prostate cancer on initial biopsy. Due to a negative initial biopsy, yet a high suspicion of cancer, 12 (6.4%) patients underwent at least 1 repeat biopsy. Of these 12 men 6 (50%) were diagnosed with cancer on repeat biopsy. Overall, 163 of the 187 men (87.2%) were diagnosed with prostate cancer by biopsy. Stratified by PSA ranges, positive predictive values were 73.6% for 20 to 29.9, 90.3% for 30 to 39.9, 93.8% for 40 to 49.9, 100% for 50 to 99.9, 95% for 100 to 199.9 and 100% for greater than or equal to 200 ng./ml. Using PSA cutoffs positive predictive values were 95.7% for PSA greater than or equal to 30, 97.6% for PSA greater than or equal to 40 and 98.5% for PSA greater than or equal to 50 ng./ml. CONCLUSIONS: Serum PSA, when increased above 50 ng./ml., is 98.5% accurate in predicting the presence of prostate cancer on tissue biopsy. Nonetheless, since transrectal prostate biopsy has a low complication rate and is relatively well tolerated, we recommend continuing to biopsy most patients with high PSA levels. However, carefully selected elderly patients on chronic anticoagulation, with severe co-morbidities or presenting with spinal cord compression may not require biopsy before androgen ablative therapy since PSA is highly accurate in diagnosing prostate cancer at levels greater than 50 ng./ml.     

Prostate specific antigen based biennial screening is sufficient to detect almost all prostate cancers while still curable

PURPOSE: We evaluated whether biennial screening with prostate specific antigen (PSA) only is sufficient to detect prostate cancer while still curable. MATERIALS AND METHODS: In G?teborg, Sweden 9,972 men 50 to 65 years old were randomized to PSA screening. During 1995 and 1996 these men were invited for a first PSA screening and invited during 1997 and 1998 for a second screening. The screening procedure included PSA measurement in all men and in those with a PSA of 3 ng./ml. or greater also it included digital rectal examination, transrectal ultrasound and sextant biopsies. RESULTS: In the first screening 5,854 men participated and 145 cancers were detected. In the second screening 5,267 men participated and 111 cancers were detected. Only 9 interval cancers were diagnosed. In the second screening 102 cancers (92%) were associated with PSA less than 10 ng./ml. Of 465 men with increased PSA and who underwent biopsy with a benign outcome in the first screening 50 had cancer at the second screening. Of 241 men in whom PSA increased between screenings 1 and 2 cancer was detected in 46. None of the 2,950 men with an initial PSA of less than 1 ng./ml. had a PSA of greater than 3 ng./ml. or interval cancer. CONCLUSIONS: In men with a PSA of less than 2 ng./ml. it seems safe to offer repeat screening after 2 years with PSA only. Men with a PSA of 2 to 3 ng./ml. or a value of greater than 3 ng./ml. with negative biopsy may be better served by a shorter screening interval. Thus, different screening intervals are implied depending on baseline PSA.     

Retrospective evaluation of PSA density for selection of biopsy candidates with prostate specific antigen in the gray zone

PURPOSE: We examined the usefulness of prostate specific antigen density (PSAD) for selection of biopsy candidate with prostate specific antigen levels between 4.1 and 10.0 ng./ml. in prostate cancer screening retrospectively. MATERIALS AND METHODS: The screening was conducted on male candidates in Natori city, aged 55 years or older, for 6 years from 1994 through 1999. We could analyze serum PSA levels and PSA density in 118 men with PSA levels between 4.1 and 10.0 ng./ml. All of 118 men underwent ultrasound guided systematic prostate biopsy regardless of findings of digital rectal examination and transrectal ultrasound. Prostate volume was estimated by transrectal ultrasound measurements using the prolate ellipse formula (pi/6 x length x width x height). PSAD was calculated by dividing serum PSA level by prostate volume. Serum PSA levels were determined by Tandem-R assay. RESULTS: In 118 men, twenty-five men had prostate cancer. There was no significant difference in mean PSA between those with prostate cancer and those without prostate cancer, but the difference was significant in the mean PSA density (mean 0.26 and 0.16, respectively, p < 0.0001). Receiver operating characteristic curves for PSA and PSAD demonstrated superior benefit for PSAD in 118 men. A sensitivity, a specificity, a positive predictive value and a negative predictive value of PSAD cut-off of 0.15 were 88%, 52.7%, 33.3% and 94.2%. PSAD cut-off of 0.18 showed the highest sum of sensitivity and specificity, which gave a sensitivity of 80%, a specificity of 72%, a positive predictive value of 43.5% and a negative predictive value of 93.1%. PSAD cut-off of 0.15 would seem to be preferable to cut-off of 0.18 because of less cancer missing. CONCLUSIONS: Although further studies are needed to determine optimal cut-off value to be used in clinical practice, PASD seems to be useful for the selection of biopsy candidates with PSA levels of 4.1 to 10.0 ng./ml. in the prostate cancer screening.     

A prospective study to evaluate the role of complexed prostate specific antigen and free/total prostate specific antigen ratio for the diagnosis of prostate cancer

PURPOSE: Patients are increasingly undergoing prostatic biopsy to identify localized prostate cancer. The decision to perform a biopsy is often made on the basis of total prostate specific antigen (PSA). However, this value lacks adequate specificity for this task. We evaluate the role that a number of these tests, including the Bayer complexed PSA (Bayer Diagnostics, Tarrytown, New York) and free/total PSA ratio, may have in our clinical practice. MATERIALS AND METHODS: A total of 160 consecutive patients attending a prostate assessment clinic were enrolled during an 18-month period in our study. All patients had a previously recorded total PSA (range 2.6 to 20.0 ng./ml.). Before transrectal ultrasound biopsy of the prostate gland, a blood sample was taken with patient consent. The findings on ultrasound were then recorded, including prostate volume. Serum samples were immediately sent for subsequent storage and analysis. RESULTS: Of the patients enrolled 109 had benign histology while 51 had prostatic carcinoma. The 2 patient groups were well matched for age. In our series patients with prostate cancer had significantly smaller prostates and higher mean total PSA. At a high sensitivity, such as 95%, it appeared that Bayer complexed PSA performed better than the other tests and ratios, with an estimated specificity of 24.8% compared with 17.4% for Bayer total PSA and 15.6% for Abbott free/total PSA (Abbott Laboratories, Abbott Park, Illinois). Receiver operator characteristics curves were drawn, and when the areas under them were calculated, we demonstrated that the area under the curve for Bayer complexed PSA (0.706) was between the values for total PSA (0.671) and free/total PSA ratio (0.731). However, the only statistically significant improvement in performance was in Bayer complexed PSA over the total PSA assays. CONCLUSIONS: Our study revealed that the overall diagnostic performance of Bayer complexed PSA appears to be better than the other PSA tests and ratios studied. The use of Bayer complexed PSA may lead to a reduction in the number of men undergoing unnecessary prostatic biopsy.     

Leukocytospermia in spinal cord injured patients is not related to histological inflammatory changes in the prostate

PURPOSE: Patients with spinal cord injuries have abnormal seminal plasma, which contributes to impaired sperm motility and viability. A common finding in these patients is an elevated leukocyte count in semen. We examined the prostatic tissue of spinal cord injured patients vs young healthy controls to determine whether a pathological process related to the prostate gland is a possible source of leukocytospermia. MATERIALS AND METHODS: Seven men with a mean age of 26.1 years with spinal cord injury and 4 controls with a mean age of 35.0 years underwent standard transrectal ultrasound guided prostate biopsy. Semen analyses were performed prior to biopsies. At least 3 biopsy cores were obtained from each prostate and all underwent routine hematoxylin and eosin staining. RESULTS: No significant abnormalities were found in any prostate biopsy cores. Two spinal cord injured patients had minor evidence of prostatic inflammation in 1 core. No inflammation was seen in any control specimens. None of the specimens showed signs of malignancy. CONCLUSIONS: Prostate biopsies obtained in this study did not show any signs of a chronic or acute significant inflammatory process that could explain increased leukocytospermia seen in patients with spinal cord injury.     

Prostate cancer detection at low prostate specific antigen

PURPOSE: At low prostate specific antigen (PSA) the indication for prostate biopsy is usually an abnormal digital rectal examination. We evaluate the diagnostic value of PSA, digital rectal examination, transrectal ultrasonography and tumor characteristics at low PSA (0 to 4.0 ng./ml.). We confirm and add to recent evidence that digital rectal examination has a low predictive value and that many significant cancers at this PSA range may be missed. MATERIALS AND METHODS: From 1994 to 1997 a total of 10,523 participants 54 to 74 years old were randomized to screening in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer. Of the participants 9,211 (87.5%) had PSA less than 4.0 ng./ml., and underwent digital rectal examination and transrectal ultrasonography. Expected rates of prostate cancer detection were calculated using logistic regression analysis. Radical prostatectomy was performed in about half of the 478 men diagnosed with prostate cancer. Tumors were characterized by pT category, Gleason score and cancer volume in 166 processed radical prostatectomy specimens. In 50 of these cases PSA was 0 to 4.0 ng./ml. RESULTS: The positive predictive value of digital rectal examination and transrectal ultrasonography at PSA 0 to 4.0 ng./ml. was only 9.7%. Positive predictive value strongly depended on PSA. Sensitivity was calculated by using estimates of the prevalence of sextant biopsy detectable prostate cancers. Of 760 detectable cancers 478 (67%) were diagnosed irrespective of PSA in men screened with digital rectal examination, transrectal ultrasonography and PSA. Only 127 of 348 detectable prostate cancers (36.5%) were actually diagnosed in men with PSA 2 to 4 mg./ml. The importance of these missed cancers was evaluated with parameters of tumor aggressiveness within PSA ranges. CONCLUSIONS: Approximately half of the tumors missed with PSA 0 to 4 ng./ml. had aggressive characteristics (Gleason score 7 or greater, Gleason 4-5 components) and were organ confined. These tumors should be diagnosed and treated according to the present understanding of their natural history. More sensitive and selective screening strategies are needed. Presently a wrong "window of opportunity" is used for early detection of prostate cancer.     

Insulin-like growth factor-1 and insulin-like growth factor binding protein-3 for prostate cancer detection in patients undergoing prostate biopsy

PURPOSE: Laboratory and epidemiological studies suggest that high circulating insulin-like growth factor (IGF)-1 and low IGF binding protein-3 are associated with increased prostate cancer risk. However, the usefulness of serum IGF-1 or IGF binding protein-3 for predicting pathology results in men undergoing prostate biopsy is unclear. We examined the relationships of serum IGF-1, IGF binding protein-3 and the results of prostate biopsy. MATERIALS AND METHODS: A total of 652 consecutive patients with elevated serum prostate specific antigen (PSA) or abnormal digital rectal examination who were referred for transrectal ultrasound sextant prostate needle biopsy underwent blood sampling before biopsy. PSA, free PSA, IGF-1 and IGF binding protein-3 were measured. There were 244 men (37.4%) with cancer and 408 controls with benign conditions. RESULTS: Mean IGF-1 plus or minus SD in the cancer and control groups was 176.1 +/- 58.3 and 178.7 +/- 54.7 ng./ml., respectively (p = 0.57). Mean IGF binding protein-3 in the cancer and control groups was 2,724 +/- 647 and 2,673 +/- 589 ng./ml., respectively (p = 0.3). Adjustment for age and PSA showed significantly lower IGF-1 in cancer cases, while IGF binding protein-3 was not significant. ROC values were significantly higher for free-to-total PSA and PSA than for crude and age adjusted IGF-1 and IGF binding protein-3. CONCLUSIONS: Our data indicate that serum IGF-1 or IGF binding protein-3 does not predict the results of prostate biopsy in men with elevated PSA or abnormal digital rectal examination. This finding implies that while there is evidence that the IGF-1 level is a risk factor for prostate cancer, neither IGF-1 nor IGF binding protein-3 can be used as a tumor marker for this disease.     

The changing pattern of prostate cancer at the time of diagnosis: characteristics of screen detected prostate cancer in a population based screening study

PURPOSE: We describe the clinical and pathological features of prostate cancer diagnosed through serum prostate specific antigen (PSA), digital rectal examination and transrectal ultrasonography in a population based randomized screening study. MATERIALS AND METHODS: Between November 1993 and June 1997, 20,632 volunteers 55 to 76 years old were included in the study. In the screening arm 9,776 men underwent digital rectal examination, transrectal ultrasound and serum PSA determination. Biopsies were taken if the digital rectal examination and/or transrectal ultrasound findings were abnormal or if PSA was 4 ng/ml or greater. A total of 2,262 men underwent biopsy and 474 cases of prostate cancer were diagnosed. RESULTS: The pretreatment data were complete in 459 men, of whom 78% had clinically organ confined disease. Bone or lymph node metastases were seen in 8 cases (1.7%). Of 172 men who underwent radical prostatectomy 2 had lymph node metastases. Overall 66.3% of men treated with radical prostatectomy had organ confined disease. CONCLUSIONS: Comparison of the characteristics of prostate cancer detected through screening of the general population with those in a population based cohort of men in which there was no organized screening revealed stage reduction, primarily with regard to number of metastatic cases. Whether this stage reduction will lead to a decrease in disease specific mortality remains unknown until the study is completed and the end point of prostate cancer specific mortality is evaluated.     

A prospective randomized trial comparing 6 versus 12 prostate biopsy cores: impact on cancer detection

PURPOSE: Several studies suggest that sextant transrectal ultrasound guided biopsy of the prostate provides insufficient material to detect all clinically important prostate cancer, and obtaining more biopsy cores may improve the cancer detection rate. We performed a prospective randomized trial comparing 6 to 12 prostate biopsy cores to determine the impact on the cancer detection rate. MATERIALS AND METHODS: We prospectively randomized 244 men, including 71 (29%) black men, with a mean age plus or minus standard deviation of 65 +/- 8 years to undergo biopsy with 6 or 12 peripheral zone tissue cores. In our study subjects serum total prostate specific antigen (PSA) was between 2.5 and 20 ng./ml., and/or digital rectal examination was suspicious for cancer. All men completed a self-administered pre-biopsy and 2 post-biopsy questionnaires at 2 and 4 weeks. Cancer detection rates were compared in the groups and correlated with race, biopsy history, digital rectal examination findings, total PSA, transrectal ultrasound volume and PSA density, as determined by the formula, total PSA/transrectal ultrasound volume. RESULTS: The cancer detection rate in the 6 and 12 core groups was almost identical (26% and 27%, p = 0.9). There was no significant difference in cancer detection in the 2 trial arms with respect to subject race, biopsy history, digital rectal examination findings, total PSA, transrectal ultrasound volume or PSA density. However, our study did not have the statistical power to rule out small differences. CONCLUSIONS: The overall cancer detection rate is not materially increased by 12 core, peripheral zone biopsy in men in whom prostate cancer was mainly detected by screening.     

Prevalence and Predictors of a Positive Repeat Transrectal Ultrasound Guided Needle Biopsy of the Prostate

Purpose

We determined the prevalence of and risk factors for carcinoma in patients with 1 previously negative prostate biopsy.

Materials and Methods

Transrectal ultrasound guided prostate needle biopsies were repeated in 130 men. Risk factors analyzed included age, pathological result of initial biopsy, inter-biopsy interval, prostate specific antigen (PSA), PSA density, PSA velocity, digital rectal examination, abnormal transrectal ultrasound and family history of prostate cancer.

Results

A total of 39 patients (30%) had positive biopsies for cancer. Univariate analysis revealed that PSA more than 20 ng./ml. and abnormal transrectal ultrasound were more frequent in men with positive second biopsies. Using multivariate logistic regression analysis only PSA more than 20 ng./ml. was a significant risk factor (adjusted odds ratio 4.48, 95% confidence interval 1.02 to 20.1). We determined the incidence of carcinoma in patients who represent the lowest risk group as defined by PSA less than 10 ng./ml., PSA density less than 0.15 mg./ml./cm.³, PSA velocity less than 0.75, ng./ml. per year, no prostatic intraepithelial neoplasia plus negative transrectal ultrasound, digital rectal examination and family history. Of 21 patients who fit this cohort 5 (23.8%) had carcinoma on repeat biopsy.

Conclusions

A significant false-negative rate for initial transrectal ultrasound guided prostate biopsies exists. Baseline risk in lowest risk patients is sufficiently high such that one cannot define a subset of patients for whom repeat biopsy is unnecessary. We recommend repeat biopsy in all patients who meet the criteria for a transrectal ultrasound guided biopsy and in whom the initial biopsy is negative.     

PROSTATE CANCER DIAGNOSIS USING A SATURATION NEEDLE BIOPSY TECHNIQUE AFTER PREVIOUS NEGATIVE SEXTANT BIOPSIES

PURPOSE: We hypothesized that markedly increasing the number of cores obtained during prostate needle biopsy may improve the cancer detection rate in men with persistent indications for repeat biopsy. MATERIALS AND METHODS: We performed saturation ultrasound guided transrectal prostate needle biopsy in 224 men under anesthesia in an outpatient surgical setting in whom previous negative biopsies had been performed in the office. The mean number of previous sextant biopsy sessions plus or minus standard deviation before saturation biopsy was 1.8 (range 1 to 7). A mean of 23 saturation biopsy cores (range 14 to 45) were distributed throughout the whole prostate, including the peripheral, medial and anterior regions. Indications for repeat biopsy were persistent elevated serum prostate specific antigen (PSA) in 108 cases, persistent elevated PSA and abnormal rectal examination in 27, persistent abnormal rectal examination in 4, high grade prostatic intraepithelial neoplasia in the previous biopsy in 64 and atypia in the previous biopsy in 21. RESULTS: Cancer was detected in 77 of 224 patients (34%). The number of previous negative sextant biopsies was not predictive of subsequent cancer detection by saturation biopsy. Median PSA was 8.7 ng./ml. and median PSA velocity was 0.63 ng./ml. yearly. Of the 77 patients in whom cancer was detected radical prostatectomy was performed in 52. Pathological stage was pT2 in 48 patients and pT3 in 4, while Gleason score was 4 to 5, 6 to 7 and 8 in 5, 46 and 1, respectively. At prostatectomy median cancer volume was 1.04 cc and 85.7% of removed tumors were clinically significant, assuming a 3-year doubling time. The overall complication rate for saturation needle biopsy was 12% and hematuria requiring hospital admission was the most common event. CONCLUSIONS: Saturation needle biopsy of the prostate is a useful diagnostic technique in men at risk for prostate cancer with previous negative office biopsies. This technique allows adequate sampling of the whole prostate gland and has a detection rate of 34% in this cohort of patients.     

CHARACTERISTICS OF SCREENING DETECTED PROSTATE CANCER IN MEN 50 TO 66 YEARS OLD WITH 3 TO 4 NG./ML. PROSTATE SPECIFIC ANTIGEN

Purpose

We defined the yield and nature of prostate cancer in the setting of population based, randomized prostate specific antigen (PSA) guided screening in men with PSA levels between 3 and 4 ng./ml. who were 50 to 65 years old at the time of randomization.

Materials and Methods

Sextant biopsies were performed in 243 men with PSA of 3 to 4 ng./ml. Therapy decisions were based on core cancer length, histological grade and life expectancy.

Results

Of the men 32 (13.2%) had prostate cancer constituting 23% of all of the 137 prostate cancers to date detected in the first round of our screening study. Age and PSA were similar in men with and without prostate cancer. Men with prostate cancer had significantly lower free PSA and free-to-total PSA ratio, and higher PSA density. Cancer was clinical stage T1c in 27 cases and stage T2 in 5. Hypoechoic areas were noted at transrectal ultrasound in 10 cases. Digital rectal examination and transrectal ultrasound were normal in 21 cases (66%). To date 14 patients have undergone prostatectomy. Surgical specimens showed a mean tumor volume of 1.8 cc (range 0.6 to 4.4) and significant amounts of high grade tumor were present in only 3 cases. Margins were positive in 5 cases, and pathological stage was pT2 in 8 cases and pT3 in 6.

Conclusions

By lowering the PSA cutoff from 4 to 3 ng./ml. an increase in cancer detection by 30% was achieved. While the addition of free-to-total ratio and PSA density may reduce the number of biopsies by about 15% with sensitivity maintained at 90%, systematic sextant biopsies were necessary in most of these men as 66% of the tumors were negative on transrectal ultrasound and digital rectal examination. The majority of these cancers were clinically significant and suitable for curative treatment. If therapy decisions are based on the pathological findings of the biopsies, the risk of treating insignificant cancers seems low.     

Evaluation of the effect of spinal cord injury on serum PSA levels

OBJECTIVES: Prostatic structure and secretory activity are thought to be influenced by autonomic innervation of the prostate. Prostatic denervation is especially likely in patients with spinal cord injury (SCI) at the level of the cauda equina or the conus medullaris, where the peripheral nerve supply to the prostate may be specifically damaged. This may result in changes in serum prostate-specific antigen (PSA) levels, either directly or indirectly. Therefore, we measured serum PSA levels and also studied the influence of factors such as age, catheterization, duration of SCI, urinary tract infection, and history of cystitis on serum PSA values in men with SCI. METHODS: Serum PSA levels were determined in 79 men with SCI (age older than 40 years) using banked sera by the Abbott MEIA PSA assay. Variables such as age, catheterization, duration of SCI, urine culture results, and history of cystitis were obtained from a review of patient records. Comparisons were made with a randomly selected, non-SCI control population of 501 men, 40 to 89 years old, who underwent serum PSA determination at our institution. Statistical comparisons were performed using the Mann-Whitney U test (nonparametric), since the populations were not normally distributed. Multivariate logistic regression analysis was used to assess the correlation between the various factors and the serum PSA levels in men with SCI. RESULTS: No statistically significant differences were found in the median serum PSA values between the SCI group and the non-SCI control population. The age-specific PSA values obtained in the SCI group were also comparable to those reported for the general population at large. Age (P <0.03) and the presence of a catheter (P <0.0002) were the only two factors that were correlated with higher serum PSA values in the SCI group by regression analysis. CONCLUSIONS: Men with SCI tended to have serum PSA value distributions that were similar to those of the general population. However, those in the SCI group who had indwelling catheters were more likely to have higher PSA values at baseline, as were older men with SCI.     

The significance of early detection for prostate cancer in mass screening

PURPOSE: In Mitaka city, mass screening for prostate cancer was conducted for 3 years from 1995 to 1997. Clinical stages were compared between patients found by screening and those diagnosed at our clinic during the same time. The significance of serum-free prostate specific antigen (PSA) in mass screening for prostate cancer was examined. MATERIAL AND METHODS: A prospective clinical trial was conducted on men aged 50 years or older. The primary examination consisted of taking the international prostate symptom score, quality of life score, PSA (Tandem-R) and digital rectal examination (DRE). If PSA was greater than 4.0 ng./ml and/or if DRE suggested cancer, transrectal ultrasound-guided sextant prostate biopsies were indicated. RESULTS: Of the men screened, 23.2% (320/1375) had serum PSA greater than 4.0 ng./ml. and/or suspicious findings on DRE. Biopsy was performed in 199 of 320 (62.1%). Cancer was detected in 21 (1.5%, 21/1375). Prostate cancer was found in one case among 154 males (0.65%, 1/154) who were screened twice or more. The cancer stage found by screening was significantly earlier than that diagnosed at the outpatient clinic (Wilcoxon's rank-sum test: p = 0.0047). Receiver operating characteristics analysis showed that the optimal free PSA-to-PSA ratio was 12%. Positive predictive value increased from 18% to 50% when free PSA-to-PSA ratio was combined with PSA. CONCLUSION: 1. Cancer detection rate was 1.5% in the mass screening in Mitaka City. 2. Cancer stage found by screening was significantly earlier than that diagnosed at the outpatient clinic. 3. Free PSA determination might eliminate unnecessary biopsies in men with PSA above 4.0 ng./ml with minimal loss of cancer detection.     

Prospective identification of National Institutes of Health category IV prostatitis in men with elevated prostate specific antigen

PURPOSE: Although prostatitis may cause elevated prostate specific antigen (PSA), asymptomatic patients are not routinely screened for this diagnosis before transrectal biopsy is performed to rule out cancer. Many negative biopsies reveal evidence of prostatitis classified as National Institutes of Health (NIH) category IV prostatitis or asymptomatic inflammation. To our knowledge this report represents the initial study of the incidence of NIH category IV prostatitis in men before biopsy and its clinical significance. MATERIALS AND METHODS: From 1996 to 1998 asymptomatic men with elevated PSA levels were evaluated for laboratory signs of prostatitis. Patients with expressed prostatic secretions or post-prostate massage urine (voiding bottle 3 [VB3]) positive for greater than 20 and greater than 10 white blood cells per high power field, respectively, received antibiotics for 4 weeks and were reevaluated after 6 to 8 weeks. Men without these clinical signs promptly underwent biopsy. Those with acute urinary tract infection and PSA greater than 30 ng./ml., without a rectum or who refused biopsy were excluded from study. RESULTS: Of the 187 study patients 122 were evaluable with a mean PSA of 9.35 ng./ml., including 51 (42%) with laboratory signs of prostatitis. After treatment PSA was normal in 22 cases and remained elevated in 29, including 9 in which biopsy revealed cancer. The change or improvement in PSA was significantly greater in men with benign results than in those with prostate cancer (-21.32 versus -1.33%, p = 0.001). In the cohort with negative expressed prostatic secretion and VB3 results transrectal ultrasound guided biopsy was done promptly. Screening decreased the number of biopsies by 18% (22 of 122 cases). The positive predictive value of PSA for detecting biopsy proved cancer improved with screening for prostatitis (45 of 122 cases or 37% versus 36 of 71 or 51%). Long-term followup revealed continued normal or stable PSA in the prostatitis cohort. CONCLUSIONS: Screening for NIH category IV prostatitis should be considered in men with elevated PSA. Although patients may be asymptomatic, anxiety caused by prostate cancer and diagnostic procedures contributes to the clinical significance of this disorder.     

Usefulness of PSA screening in outpatients with bladder cancer: Preliminary results

BACKGROUND: We performed prostate-specific antigen (PSA) screening and evaluated its usefulness in outpatients with bladder cancer who may have an elevated risk for prostate cancer. METHODS: Sixty-one new or followed-up outpatients with bladder cancer were examined between September 1999 and December 2000 in the Department of Urology, Gunma University Hospital, Japan. PSA was measured after informed consent was obtained, and patients in whom the PSA level was 4.1 ng/mL or higher were selected for thorough examination. In the examination, one examiner performed DRE (digital rectal examination) and, based on DRE and TRUS (transrectal ultrasonography) findings, determined whether prostate biopsy was indicated. RESULTS: The average age of the 61 cases was 69.1 +/- 8.6 years, and the average PSA level was 3.5 +/- 5.8 ng/mL. The PSA level was 4.1 ng/mL or higher in 11 (18.0%) patients, nine of whom underwent six-sextant biopsy under TRUS guidance. Of these nine cases, four (6.6%) were diagnosed as having prostate cancer. The Gleason score was 7 in three cases and 9 in one case. The clinical stage was T2N0M0 in three cases and T3N0M0 in one case. CONCLUSIONS: On PSA screening in patients with bladder cancer and patients with a history of transurethral resection of the bladder tumor (TUR-BT), prostate cancer was found in 6.6%. This rate is higher than in the general population. These cancers were classified into intermediate to high-risk groups, and the prognosis of prostate cancers could be more important than those of the bladder cancers in two cases (50%). We conclude that PSA screening for inpatients with bladder cancer may be useful.     

Prostate specific antigen predicts the long-term risk of prostate enlargement: results from the Baltimore Longitudinal Study of Aging

PURPOSE: Prostate specific antigen (PSA) is a predictor of prostate growth in men with lower urinary tract symptoms. The long-term risk of prostate enlargement as a function of PSA among community dwelling volunteers is unknown. MATERIALS AND METHODS: A Cox proportional hazards regression model was used to study the relationship between baseline PSA level at ages 40 to 49.9 years in 194 men, 50 to 59.9 in 191 and 60 to 69.9 in 144, and prostate enlargement, defined as a prostate volume larger than the 75th percentile for age decade, as measured by magnetic resonance imaging in a longitudinal study of aging (Baltimore Longitudinal Study of Aging, National Institute on Aging). Kaplan-Meier survival analysis was performed to estimate the probability of freedom from prostate enlargement with time as a function of baseline PSA level. RESULTS: The relative risk of prostate enlargement was 3- to 6-fold higher for men 40 to 49.9 years old with a baseline PSA of 0.31 ng./ml. or more compared to men with PSA levels of 0.30 ng./ml. or less at baseline. The relative risk was increased 5- to 9-fold in men 50 to 59.9 years old and 11-fold in those 60 to 69.9 years old when comparing men with PSA greater than 0.80 ng./ml. and greater than 1.70 ng./ml. with those with PSA 0.50 or less. The cumulative probability of freedom from prostate enlargement at 20 years was 0.89 (95% confidence interval ([CI] 0.79-0.99) and 0.63 (0.52-0.74) for men 40 to 49.9 years old with PSA levels below and above 0.30 ng./ml., respectively. For men 50 to 59.9 years old the 10-year probability of freedom from prostate enlargement was 0.90 (95% CI 0.84-0.96) and 0.59 (0.43-0.74) when PSA levels were below and above 0.80 ng./ml., respectively. At age 60 to 69.9 years the 10-year probability of freedom from prostate enlargement was 0.83 (95% CI 0.72-0.93) and 0.27 (0.09 to 0.48) when PSA levels were below and above 1.70 ng./ml., respectively. CONCLUSIONS: These data demonstrate the long-term risk of prostate enlargement by PSA level. Risk stratification based on PSA level may be useful to identify men at greatest risk for adverse events due to prostate enlargement and selection of men for future benign prostatic hyperplasia studies.     

Can Free and Total Prostate Specific Antigen and Prostatic Volume Distinguish Between Men With Negative and Positive Systematic Ultrasound Guided Prostate Biopsies?

Purpose

We evaluated the role of free and total serum prostate specific antigen (PSA) and prostate volume in discriminating between men with negative and positive transrectal ultrasound guided biopsies.

Materials and Methods

A total of 104 consecutive men with a positive biopsy and at least 3 mm. of prostate cancer was compared to 110 consecutive men with a negative biopsy. Prostate volume was determined by transrectal ultrasound. Total PSA was determined by the Tosoh AIA-600† PSA assay and free PSA was measured by the PSA II Dianon‡ assay. We determined the free-to-total PSA ratio, free and total PSA densities, and the relationship of free PSA and free-to-total PSA ratio to prostate volume.

Results

Using a 23% cutoff value of free-to-total PSA, only 22.7% of biopsies were preventable in patients with a negative biopsy but 9.6% of the cancers were missed. At a total PSA of 4 to 10 ng./ml. 44.4% of the biopsy negative cases were correctly identified while missing 9.1% of the cancers if a 20% free PSA cutoff is used. For total PSA more than 10 ng./ml. an 18% free PSA cutoff properly identified 30.2% of the biopsy negative cases while missing 9.3% of the cancers. Percent free PSA is a better discriminant than prostate volume for total PSA more than 4 ng./ml. and the combination was not helpful. Free PSA density was identical in patients with negative and positive biopsies. There was no relationship between free PSA or free-to-total PSA ratio levels and prostate volume.

Conclusions

Use of a single discriminant criterion of free-to-total PSA ratio in the practical clinical setting of distinguishing negative and positive biopsies appears useful in patients with a total PSA of 4 to 10 ng./ml. Since free PSA is unrelated to prostate volume in biopsy negative and positive cases the physiological basis of free PSA is an enigma.     

Prostate cancer screening at an equal access tertiary care center: its impact 10 years after the introduction of PSA

INTRODUCTION AND OBJECTIVES: Dwight D. Eisenhower Army Medical Center has been involved in Prostate Cancer Awareness Week (PCAW) screening during the period 1995-2000. The purpose of this study is to review the results of screening in a self-selected population of military beneficiaries at our institution. MATERIALS AND METHODS: Screening involving a brief urologic history, digital rectal examination (DRE) and serum prostatic specific antigen (PSA) measurement was offered to our screening population. Patients with an elevated PSA (>4.0 ng/ml) and/or a suspicious DRE were considered for transrectal ultrasonography with prostate needle biopsy (TRUS/PNB). Patient health records were reviewed retrospectively and analyzed to determine patient demographic characteristics, PSA distribution, DRE results and cancer detection rates. RESULTS: A total of 455 screening visits were performed from 1995 to 2000, of which 426 visits were included for analysis. Mean age of the study population was 57.4 y (40-83). Seventy-one percent of the patients reported prior PSA screening visits. Forty-four patients met indications for biopsy. A total of 30 TRUS/PNB were performed demonstrating presence of cancer in three patients for an overall cancer detection rate of 0.7%. CONCLUSIONS: Our study shows that the overall prostate cancer detection rate at our institution is lower than detection rates previously reported in the literature. Potential reasons for this finding may include that the subjects participating in PCAW screening tended to be younger than in other series and that a majority of them had already undergone prior screening. These findings suggest the need to modify prostate cancer screening recommendations and to improve prostate cancer screening efficacy.