How to use prostate-specific antigen in the early detection or screening for prostatic carcinoma.

Prostate Specific Antigen Isoforms and Human Glandular Kallikrein 2—Which Offers the Best Screening Performance in a Predominantly Black Population?

The TOSOH II PA (AIA-PACK PA in the U.S.A.) monoclonal immunoenzyme assay was used and the clinical usefulness of prostate specific antigen (PSA) was evaluated in 39 men with prostatic cancer and 32 men with benign prostatic hyperplasia (BPH) confirmed pathologically. We evaluated the lower limit of detection in this assay by the mean PSA level plue 3 standard deviations in 5 separate experiments with a zero control sera as well as the mean PSA level minus 3 standard deviations in 5 separate experiments with serial dilutions of a known concentration of PSA. PSA concentrations of 0 to 0.25 ng/ml could not be distinguished from the zero control. Therefore, we set the lower limit of detection for the assay as 0.25 ng/ml. At our laboratory, the normal standard value was determined by the mean PSA level plus 3 standard deviations in 79 healthy men as 2.3 ng/ml. Of patients that underwent radical cystoprostatectomy for bladder cancer, all had PSA levels less than 0.25 ng/ml, while only 6% had PAP levels less than 0.11 ng/ml, the lower limit of detection in the TOSOH II PAP assay. We compared TOSOH II PA with Markit PA, a commonly used assay in Japan. Although there was a close linear correlation (r = 0.90) between the TOSOH II PA and Markit PA, the difference of slope in the linear regression lines was great, it was thought due to anti-PSA antibodies in each assay recognizing different epitopes of PSA in the blood.(ABSTRACT TRUNCATED AT 250 WORDS)

This study was undertaken to assess the utility of prostate specific antigen (PSA) and PSA density (PSAD) in discriminating between benign and malignant prostate disease in the Kuwaiti Arab population. A total of 100 consecutive patients suspected of having prostate cancer because of serum PSA > 4 ng/ml, or detection of a prostatic nodule on rectal examination were further investigated by determination of PSAD, TRUS of prostate, sexant prostatic biopsy and histological analysis to establish the correct diagnosis. Other diagnostic measures included the determination of the area under the receiver operating characteristic (ROC) curve, sensitivity and specificity. Of the 100 prostate biopsies that were performed, 33 cases were confirmed to be prostate cancer and 67 were described as benign lesions comprising benign prostatic hyperplasia (BPH) with or without prostatitis. The age range for patients with prostate cancer was 42-90 years, and 52-90 years for those without prostate cancer. The mean prostate volume was 58.82 cc (range 9-177 cc) and 62.60 cc (range 15-140 cc), the mean PSA value was 36.65 ng/ml (range 5.8-200 ng/ml) and 16.49 ng/ml (range 1.4-46.0 ng/ml), while the mean PSAD was 0.92 (range 0.046-5.714) and 0.452 (range 0.034-2.294) for patients with prostate cancer and patients without prostate cancer respectively. Patients with PSA less than 4 ng/ml (3 cases) all had benign prostate lesions, and 7 cases with PSA more than 50 ng/ml all had prostate cancer and were excluded because values above 50 ng/ml have close to 100% specificity for prostate cancer. Further analysis was done on the remaining 90 cases which were patients with a PSA between 4 and 50 ng/ml. The discriminating power of serum PSA for detecting prostate cancer as estimated by the area under ROC was 0.686 while that for PSAD was 0.732. The maximum likelihood for a positive PSA was at a PSAD cut-off point of 0.32. For the PSA cut-off point of l0 ng/ml, the sensitivity was 80%, and specificity was 42.2%. For the PSAD cut-off point of 0.32, the sensitivity was 58% and the specificity 76.6%. Determination of PSAD is not a useful adjunct to serum PSA values in the range of 10-50 ng/ ml in our population. PSAD value less than 0.32 with PSA less than l0 ng/ml strongly suggests benign disease.

To evaluate the clinical significance of prostate-specific antigen (PSA) screening in early detection of prostate cancer in Chinese men. PSA screening was performed in 8562 asymptomatic men who had been enrolled for health checkup and all were > or = 50 years old. Prostate biopsy was recommended for those with a serum PSA level > or = 4.0 ng/ml. The pathological and clinical features of the patients with prostate cancer detected by the PSA screening were compared with that of 82 clinically diagnosed prostate cancer patients during the same period. Of the 8562 asymptomatic men, 719 had PSA levels > or = 4.0 ng/ml and biopsy was performed in 295 of them. Fifty-eight prostate cancers were detected. The biopsy rate was 41.0% and positive detection rate was 19.7%. The overall age distribution in the screening group and the clinical groups was not significantly different (P = 0.176). However, 41.4% (24/58) of the patients in screening group were > 75 years old, and significantly more than that in the clinical group (25.6%, P = 0.0491). The proportion of the patients with PSA levels > or = 20 ng/ml in the screening group was significantly less than that in the patients of the clinical group (44.8% vs. 75.6%, P = 0.0002). Whether in the patients whose age was > 75 years old (P < 0.05) or < or = 75 years old (P = 0.0002), the patients in the screening group had significantly lower Gleason scores < 7 (60.3% vs. 34.1%, P = 0.002), more T1 or T2 tumor (87.9% vs. 26.8%, P < 0.0001) and more chance to receive radical prostatectomy (50.0% vs. 18.3%, P < 0.0001) than the patients in the clinical group did. However, the distributions of PSA levels at diagnosis and biopsy Gleason scores were not significantly different between the above mentioned two groups (P > 0.05). Prostate-specific antigen (PSA) screening is useful for early detection of prostate cancer in Chinese men aged > or = 50 years. The patients detected by PSA screening usually show a lower PSA level, Gleason scores and early clinical stage disease, and have more chance for radical prostatectomy than the clinically diagnosed patients.

PREDICTORS OF SUBSEQUENT PROSTATE CANCER IN MEN WITH A PROSTATE SPECIFIC ANTIGEN OF 2.6 TO 4.0 NG/ML AND AN INITIALLY NEGATIVE BIOPSY

On the use of prostate-specific antigen for screening of prostate cancer in European Randomised Study for Screening of Prostate Cancer

To improve the specificity of cancer detection in patients with normal digital rectal examination and intermediate prostate specific antigen (PSA) level, PSA density has been recommended, with biopsy based on a PSA density of 0.15 or more. PSA density is reportedly higher in Japanese men than in white men, because of physiological differences between the 2 races. We prospectively evaluated PSA density as a discriminator of prostate cancer in Japanese men. We evaluated prospectively 60 consecutive men with normal digital rectal examinations and serum PSA levels of 4.1 to 10.0 ng./ml. enrolled during a 17-month period. All patients underwent transrectal ultrasound guided sextant biopsies, regardless of calculated PSA density and transrectal ultrasound findings. Serum PSA levels were determined by IMx assay. Overall, 8 of 60 men (13%) had prostate cancer. There was no significant difference in mean PSA between those with positive and those with negative biopsies, but the difference was significant in the mean PSA density (mean 0.24 and 0.15, respectively, p < 0.01). Receiver operating characteristics curves for PSA and PSA density demonstrated superior benefit for PSA density in this patient population. A reference PSA density value of 0.19 was chosen because it showed the highest sum of sensitivity and specificity, which gave a sensitivity of 75%, a specificity of 87%, a positive predictive value of 46% and a negative predictive value of 96%. The results suggest that PSA density improves the specificity of cancer detection in men with a normal digital rectal examination and an intermediate PSA level. Although further study with a larger patient population is needed to obtain a best-fit value, an optimal PSA density cutoff seems to be higher than that recommended in the literature from western countries. Because of possible racial differences in serum PSA and prostate volume, the role of PSA density in Asian men should be studied independently.

This study was undertaken to determine whether the prostate specific antigen (PSA) density (PSAD) and PSAD of the transition zone (PSADT) are useful in the detection of prostate carcinoma in Japanese men with intermediate levels of serum PSA. Two hundred and eighty-seven Japanese men with intermediate serum PSA levels (2.1 ng/mL to 10 ng/mL) underwent measurement of prostate volume by transrectal ultrasound (TRUS) and systematic biopsy under TRUS guidance. The volume of the transition zone was also measured by TRUS in 134 patients. The PSAD and PSADT were determined for each patient, and their relationship to prostate carcinoma detection was examined. Prostate carcinoma was detected in 30 of 287 patients (10.5%). Although the serum PSA levels were similar in patients with benign and malignant prostate disease (P = 0.541), the prostate volume (P 0.0009) and PSAD (P < 0.0001) differed significantly in the two groups; in the patients with prostate carcinoma, the prostate volume was smaller, and the PSAD higher, than in the patients with benign disease. At the PSAD cutoff value of 0.18 ng/mL/cm3 or greater, the sensitivity was 70% and the specificity was 67% for the diagnosis of prostate carcinoma. The PSAD was found to be significantly better in the differentiation between benign and malignant prostate disease than the serum PSA in the receiver operating characteristic analyses (P = 0.045). However, the receiver operating characteristic curve for PSAD was not significantly different compared with that for PSA in the men with negative digital rectal examination findings. Prostate carcinoma was detected in 9.0% (12 of 134) of the patients who underwent PSADT determination. Receiver operating characteristic analyses showed that PSADT was not superior to PSA in the detection of prostate carcinoma. In Japanese men with intermediate serum PSA concentrations, PSAD offers additional information useful in the detection of prostate carcinoma, but PSADT does not. Although use of PSAD may decrease the number of unnecessary biopsies, a significant number of prostate carcinomas may be overlooked. Therefore, the authors recommend that serum PSA levels continue to be used as an indicator for biopsy in Japanese men.

Clinical Characteristics and Biopsy Specimen Features in African-American and White Men Without Prostate Cancer

UP-1.115: Comparison of the Predictive Accuracy of Serum Prostate Specific Antigen Levels (PSA), Free PSA and PSA Density in the Detection of Prostate Cancer

Comparison of Prostate Specific Antigen Concentration Versus Prostate Specific Antigen Density in the Early Detection of Prostate Cancer: Receiver Operating Characteristic Curves

Since the discovery of prostate specific antigen (PSA) and its relation to prostate cancer detection, there have been countless studies attempting to improve its accuracy. “Improve detection and avoid unnecessary biopsies” has been the objective for more than 2 decades. Surprisingly, after so many years of defining and fine-tuning its use for clinical practice, the PCPT study1 painfully showed us that prostate cancer can be found no matter what level of serum PSA. In this issue of CUAJ Bolduc and colleagues2 report on their experience of measuring urinary PSA in the hopes of improving the accuracy of serum PSA in prostate cancer early detection. Although this is not the first time such an attempt has been made, these authors have made some unique observations. Despite the small number of cases, the authors observed that at a cutoff of 150 ng/mL for urinary PSA an impressive sensitivity of 92.5% was achieved. Unfortunately, there was no clear relation with cancer grade, but urinary PSA appeared to be helpful in addition to serum PSA for identifying more advanced stage cancers. Obviously, a much larger series of cases and controls is required to validate the usefulness in everyday clinical practice. For those urologists who are looking for ways to reduce unnecessary prostatic biopsies, urinary PSA may one day be added to the series of biomarkers and nomograms for such a purpose. However, for those who do not wish to miss any prostate cancers, urinary PSA will probably not be very useful. Interestingly, one can probably say the same for serum PSA. Nevertheless, if urinary PSA can indeed provide additional prognostic information over serum PSA in the low levels, then it would be most welcome.

To determine the usefulness of prostate-specific antigen (PSA) screening for prostate cancer in patients with end-stage renal disease (ESRD), as although serum PSA is effective in the early detection of this cancer in the general population, there are few reports of its utility in patients with ESRD. Blood samples were obtained for PSA screening from April 2002 to September 2003; 1250 men with ESRD aged >50 years were compared with 1007 healthy control men aged >55 years, all in Kumamoto Prefecture, Japan. All men with a serum PSA level of >4.0 ng/mL were categorized as PSA-positive and were further assessed, including a prostate biopsy. There was a statistically significantly greater increase in PSA level with age in the ESRD group than in the healthy controls. The rate of cancer detection among men with a PSA level of >10 ng/mL was significantly higher in patients with ESRD than in healthy controls. Thirteen patients with ESRD and five healthy control men were finally diagnosed with prostate cancer. The serum PSA level was slightly higher and the incidence of prostate cancer at higher PSA levels appeared to be greater in men with ESRD than in healthy controls. The findings of this large study suggest that PSA screening is useful for the diagnosis of prostate cancer in these patients.

Purpose: We prospectively evaluated the prostate cancer detection rate and pathologic characteristics of patients with a serum prostate-specific antigen (PSA) level of 3.0 to 4.0ng/ml and we compared this with the patients who had a PSA level in the range of 4.1 to 10.0ng/ml. Materials and Methods: We analyzed the data of patients who had PSA levels of 3.0 to 10.0ng/ml, benign findings on digital rectal examination (DRE) and no specific lesion identified on transrectal ultrasound. The clinical characteristics, cancer detection rate and pathologic findings of the biopsy and prostatectomy specimen were compared between the low (3.0 to 4.0ng/ml) and intermediate (4.1 to 10.0ng/ml) PSA groups. Results: A total of 370 patients met our criteria and so they were included in the study. Sixty five and 305 patients had low or intermediate PSA levels, respectively. The mean age and the number of prostate biopsy cores were not different between the two groups. Prostate cancer was diagnosed in 26% of the low PSA group and in 20% of the intermediate PSA group. No significant difference was found between the two groups on the pathologic findings of the biopsy and on the pathology findings of the prostatectomy specimens, including the mean Gleason score, the percentage of patients with a Gleason score 7 or higher, the pathologic stage and the percentage of insignificant prostate cancer. Conclusions: No statistically significant difference was found in the incidence of prostate cancer or pathological characteristics on comparison between the low and intermediate PSA groups. These results suggest that a lower PSA cutoff should be considered as an indication for a prostate biopsy in the Korean population. (Korean J Urol 2006;47:358-361) ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ

NOVEL STAGING TOOL FOR LOCALIZED PROSTATE CANCER: A PILOT STUDY USING GENETIC ADAPTIVE NEURAL NETWORKS