Higher Prostate-specific Antigen Values Research Articles

Detection of Prostate Cancer and Changes in Prostate-Specific Antigen (PSA) Six Months after Surgery for Benign Prostatic Hyperplasia in Patients with Elevated PSA

Objective: To evaluate early postoperative results of patients with elevated prostate-specific antigen (PSA) levels who underwent surgery due to benign prostatic hyperplasia (BPH). Patients and Methods: 64 patients who had lower urinary tract symptoms (LUTS), normal digital rectal examinations (DRE), elevated PSA levels and prostate biopsies reported as being benign pathologically in specimens obtained by transrectal ultrasound (TRUS)-guided biopsies, were included in the study. Patients were assessed in accordance with PSA density, free/total PSA ratio and uroflowmetric studies. Patients had no cancer pre- and postoperatively (according to operative specimens). Six months postoperatively, 32 patients were accepted for re-evaluation for all PSA parameters, routine tests and prostatic biopsies. Results: 64 patients with a mean age of 66.8 (SD 6.72) were included in the study. Total PSA average value was 14.38 (SD 7.49) ng/ml. Free PSA average value was 2.11 (SD 1.43) ng/ml. Average PSA density and free/total PSA ratio were 25.19 SD (14.12) ng/ml/cm³ and 14.53% (SD 5.35%) respectively. 56 patients had BPH, 7 had chronic prostatitis and 1 had prostatic intraepithelial neoplasia (PIN) preoperatively with biopsies. Re-biopsy of the patient with PIN was reported as BPH. In pathologic examination with resected tissues postoperatively, 49 patients had BPH, 14 had chronic prostatitis and 1 had PIN. In the sixth month, average values of free/total PSA were 0.45 (SD 0.26) and 3.71 (SD 4.96) ng/ml respectively. Average PSA density and free/total PSA ratio were 12.41 (SD 13.8) ng/ml/cm³ and 19.59% (SD 10.33%) respectively. There were significant decreases in PSA densities (p < 0.001) and increases in free/total PSA ratios (p = 0.004). Seven patients still had elevated PSA levels 6 months postoperatively. Three of 7 patients were reported as chronic prostatitis. One of them was indicated as prostatic carcinoma who was reported as PIN preoperatively. All other patients were stated as BPH at re-biopsies. Conclusion: If pretreatment biopsies are negative and operative specimens are also benign in patients with high PSA values, these patients can be followed up like usual BPH patients, but long-term follow-up is still unclear.

Prostate-specific antigen as surrogate for characterizing prostate cancer subgroups.

To evaluate how serum prostate-specific antigen (PSA) levels in a population-based cohort of men with prostate cancer vary with age and intensity in the diagnostic activity and to describe the treatment selection processes associated with PSA level. All men in the Swedish National Prostate Cancer Register diagnosed during 1996-1997 were included. In 1996 the register included 19 counties, covering 61% of the Swedish male population, and in 1997 21 counties with 79% of the Swedish male population. A total of 8328 men were registered. PSA levels were missing in 341 cases. With increasing PSA there was a shift towards more advanced and poorly differentiated tumours. PSA at diagnosis increased with age, with the exception of patients younger than 50 years who had higher PSA values. The mean logarithm of PSA correlated negatively with the percentage of localized tumours (p < 0.005) and the age-adjusted incidence (p < 0.05) in each respective county in 1997. PSA was higher in men receiving radiotherapy compared with those treated with radical prostatectomy as well as in the group treated with bilateral orchiectomy compared with those receiving GnRH-analogues. If PSA is used as a surrogate measure of extent of tumour volume in a population of prostate cancer patients, our findings indicate that age distribution and differences in incidence (possibly due to variation in diagnostic activity) should be taken into account. In our cohort there was a selection process, probably in part guided by PSA level, when choosing type of curative or palliative treatment.

Biochemical Course after Radical Retropubic Prostatectomy: Preliminary Results

Objective: To investigate prognostic factors in localized and lymphatically spread prostate cancer. Methods: The biochemical course after radical retropubic prostatectomy in 306 patients was subject to a retrospective analysis. Results: Prostate–specific antigen (PSA), Gleason score (prostatectomy specimen) and pathological stage proved to be prognostically relevant (p<0.0001). PSA, Gleason score and tumor stage also were to be considered as (independent) prognostic factors by means of a multivariate analysis (p<0.001), whereas perineural invasion (prostatectomy specimen) and preoperative bone marrow findings (CK 2) had no impact on the course of the disease. After a median follow–up of 1,307 days (3.6 years), a biochemical relapse occurred in 41.8%. Conclusion: High preoperative PSA values and the resulting high portion of advanced tumor stages are a possible basis for the high biochemical relapse rate in our collective. The learning curves of several surgeons and the previously more restrictive pelvic lymphadenectomy (surgical understaging) may also be considered causes.

Combination of signal intensity measurements of lesions in the peripheral zone of prostate with MRI and serum PSA level for differentiating benign disease from prostate cancer.

The aim of this study was to predict the benign or malignant nature of a prostatic lesion by defining a threshold value of signal intensity ratio and a limiting value of serum prostate-specific antigen (PSA) in patients with elevated PSA level. Twenty-six patients with elevated PSA level and no hypoechogenic lesions at endosonography underwent MR imaging using an endorectal body phased-array coil at 1.5 T (Siemens Magnetom Symphony). A T2-weighted turbo-spin-echo (TSE) pulse sequence was applied in a transverse orientation. Two radiologists evaluated the images. In the presence of a pathological finding they defined regions of interest (ROI) in the suspicious pathological area of the peripheral zone and in muscle for reference. The quotient of the two ROIs was calculated and then correlated with the actual PSA level. Diagnosis was confirmed by prostate biopsy. Ten of 12 patients with quotients smaller than 4 showed cancer at histology. Nine of 12 men with cancer proven by biopsy had PSA levels higher than 10 ng/ml. A significant difference (p < 0.001) was found between the quotients of cancer and quotients of chronic prostatitis, fibrosis, or glandular atrophy. The accuracy of tumor differentiation of the method was 77%. Measurement of signal intensity quotients in the peripheral zone of the prostate in combination with knowledge of defined limits of PSA levels the technique could be helpful in detecting additional cancer areas for prostate biopsy. False-negative tumor results of standard sextant biopsy can be reduced. In men with high PSA values the method has a role in differentiating between patients who require prostate biopsy and those of clinical observation.

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.

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

Background: The reported incidence of prostate cancer is higher among African-American men than among white men. We conducted a study of African-American and white men without prostate cancer to determine whether clinical and histologic findings might be associated with racial differences in serum prostate-specific antigen (PSA) levels. Methods: From January 1990 through March 1997, 493 (59.5%) of 829 African-American men and 736 (74.1%) of 993 white men who had elevated serum PSA levels (>4.0 ng/mL) and/or abnormal digital rectal examinations and who underwent transrectal ultrasound-guided prostate biopsies were found to be without prostate cancer. Also reviewed were patients’ age and race, indication for biopsy, histologic features of the prostate biopsy specimen, ultrasound-measured prostate volume, PSA density (i.e., the PSA level divided by the prostate volume), and (in some cases) serum testosterone levels. Results: Among these men without prostate cancer, there were no statistically significant differences by race in the ages of the patients, their prostate volumes, or their serum testosterone levels; however, the mean serum PSA levels and PSA densities were significantly higher in African-American men than in white men (twosided P values of .00003 and .000009, respectively). A higher proportion of African-American men than white men had inflammation in their prostate biopsy specimen, and men of both races with prostate inflammation had higher PSA values than those without inflammation. African-American men without inflammation had higher PSA values than white men without inflammation. Conclusions: In this study, African-American men without histologic evidence of prostate cancer had significantly higher PSA levels and PSA densities than similarly aged white men. This finding was not accounted for by racial differences in patients’ age, serum testosterone level, or prostate volume. [J Natl Cancer Inst 1998;90:756‐60]

Inability of bone turnover marker as a strong prognostic indicator in prostate cancer patients with bone metastasis: comparison with the extent of disease (EOD) grade.

Although clinical investigations of bone turnover markers in prostate cancer patients have been conducted, the relationships of pretreatment levels of the markers to the prognosis of patients with bone metastasis has not been fully examined. The serum levels of carboxy-terminal propeptide of type I procollagen (PICP) and carboxy-terminal telopeptide of type I collagen (ICTP), alkaline phosphatase (ALP), and prostate-specific antigen (PSA) were examined in 48 untreated prostate cancer patients with bone metastasis, and the prognoses of the patients were evaluated using univariate and multivariate analyses. The patients with low PICP or ALP values had significantly better outcomes in terms of cause-specific survival compared to the patients with high PICP or ALP values. There was no significant difference in survival between patients with high and low ICTP or PSA values. The multivariate analysis of PICP, ICTP, ALP, PSA, and extent of disease (EOD) grade revealed that only the EOD grade was an important prognostic indicator for survival. These results demonstrate that the extent of bone metastasis evaluated by bone scintigrams is a more important prognostic indicator than are the serum biochemical markers of bone turnover.

Clinical characteristics and biopsy specimen features in African-American and white men without prostate cancer.

The reported incidence of prostate cancer is higher among African-American men than among white men. We conducted a study of African-American and white men without prostate cancer to determine whether clinical and histologic findings might be associated with racial differences in serum prostate-specific antigen (PSA) levels. From January 1990 through March 1997, 493 (59.5%) of 829 African-American men and 736 (74.1%) of 993 white men who had elevated serum PSA levels (> or = 4.0 ng/mL) and/or abnormal digital rectal examinations and who underwent transrectal ultrasound-guided prostate biopsies were found to be without prostate cancer. Also reviewed were patients' age and race, indication for biopsy, histologic features of the prostate biopsy specimen, ultrasound-measured prostate volume, PSA density (i.e., the PSA level divided by the prostate volume), and (in some cases) serum testosterone levels. Among these men without prostate cancer, there were no statistically significant differences by race in the ages of the patients, their prostate volumes, or their serum testosterone levels; however, the mean serum PSA levels and PSA densities were significantly higher in African-American men than in white men (two-sided P values of .00003 and .000009, respectively). A higher proportion of African-American men than white men had inflammation in their prostate biopsy specimen, and men of both races with prostate inflammation had higher PSA values than those without inflammation. African-American men without inflammation had higher PSA values than white men without inflammation. In this study, African-American men without histologic evidence of prostate cancer had significantly higher PSA levels and PSA densities than similarly aged white men. This finding was not accounted for by racial differences in patients' age, serum testosterone level, or prostate volume.

MAGNETIC RESONANCE IMAGING OF CLINICALLY LOCALIZED PROSTATIC CANCER

Purpose We assess the accuracy of endorectal coil magnetic resonance imaging (MRI) for detecting tumor localization, capsular penetration and seminal vesicle invasion in clinically organ confined prostate cancer. We also evaluate intra-observer and interobserver agreement in interpreting MRI studies. Materials and Methods MRI studies of 51 consecutive patients a mean of 61 years old with biopsy proved prostate cancer were retrospectively read twice by 2 radiologists in random order. Both radiologists marked tumor localization, capsular penetration and seminal vesicle invasion on standard tumor maps. These findings were compared with the histopathological results of radical prostatectomy specimens. Results The overall accuracy of detecting cancer localization was 61%. The detection rate for cancer foci less than 5 mm. was only 5% but for lesions greater than 10 mm. it was 89%. There was 91 and 80% accuracy for detecting capsular penetration and seminal vesicle invasion, respectively. Sensitivity and specificity were 60 and 63, 13 and 97, and 59 and 84% for localization, capsular penetration and seminal vesicle invasion, respectively. Intra-observer and interobserver agreement ranged from fair to good (kappa coefficient 0.240 to 0.647). Conclusions Endorectal MRI seems to be better than previously reported for detecting seminal vesicle invasion and tumor foci in the anterior half of the prostate. Sensitivity in detecting minor capsular penetration of the tumor was low, which can probably be improved by methodological development. MRI may be useful for locating cancer foci in patients with high prostate specific antigen values but repeatedly negative biopsy findings.

CURRENT TRENDS IN PROSTATE CANCER DIAGNOSIS AND STAGING AMONG UNITED STATES UROLOGISTS

Purpose We analyzed current practice patterns and determined whether urologists are diagnosing and staging prostate cancer in accordance with one another and with available literature. Materials and Methods An anonymous questionnaire was mailed to 1,500 randomly selected practicing American Urological Association members throughout the United States, categorized according to practice setting and decade of residency training completion. Results There were 624 respondents (41.6%). Annual routine prostate cancer detection is being aimed toward the right of the age spectrum. More than half of respondents use age specific prostate specific antigen (PSA), while fewer than half use PSA density in determining need for biopsy. The vast majority will perform radical prostatectomy on patients whose age suggests that they will not benefit from surgery. High PSA values and Gleason scores often are disregarded as independent precluding factors when deciding to perform radical prostatectomy. Computerized tomography and radionuclide bone imaging are used routinely far in excess of what the literature suggests is appropriate. Regardless of preoperative staging results, most urologists still perform lymphadenectomy with all radical prostatectomies. Conclusions Discrepancies exist in practice patterns between urologists as well as inconsistencies in logic within individuals. There is little variation between individuals in different practice settings. Our results reflect the often confusing and conflicting data published during the last decade.

Increasing prostate-specific antigen profile following definitive radiation therapy for localized prostate cancer: clinical observations.

To examine the natural history of patients who have received definitive radiation therapy alone for clinically localized prostate cancer and have an increasing prostate-specific antigen (PSA) profile. One hundred fifty-one men with an increasing PSA profile after definitive radiotherapy were identified. The subsequent natural history of these men, including local recurrence, distant metastasis, and survival, was examined. In 119 men, posttreatment PSA doubling times (PSADT) were calculated using linear regression. Cox regression models were used to examine the effect of clinical and treatment variables on clinical failure and survival. Patients with high pretreatment PSA values, high Gleason scores, and T3 tumors were more likely to develop a PSA elevation. The median calculated post-treatment PSADT was 13 months, and 95% of patients had posttreatment PSADT of less than 3 years. PSADT was correlated with tumor stage and Gleason score. Five years after PSA elevation, the estimated rate of clinical local recurrence is 26% and the estimated rate of distant metastases is 47%. Rapid PSADT (< 12 months) and a short interval from the end of treatment to PSA elevation (< 12 months) were significant independent predictors of distant metastases. The estimated rates of overall and cause-specific survival 5 years after PSA elevation are 65% and 76%, respectively. Gleason grade is the only significant independent predictor of overall and cause-specific survival after PSA elevation. The natural history of men who have an increasing PSA profile following definitive radiotherapy is heterogeneous. In the absence of salvage therapy, at least three quarters of men will have clinical evidence of recurrent disease 5 years after a PSA elevation is detected. Men with a rapid posttreatment PSADT and a short interval from the end of treatment to an increasing PSA profile are at a very high risk of developing distant metastasis within 5 years of PSA elevation.

Value of Prostate Specific Antigen in Early Diagnosis of Prostate Cancer: Study of Men Born in 1913

Purpose We attempt to elucidate the performance of serum prostate specific antigen (PSA) as a screening test for prostate cancer. Materials and Methods We analyzed sera stored since 1980 in a nested case-control study. Results The 36 patients with prostate cancer had a markedly greater mean serum PSA level than did 68 subjects without cancer (22.71 versus 2.67, respectively, p less than 0.0001). Among the controls 24 percent had a serum PSA of greater than 4.0 microgram/l. A serum PSA value exceeding 4.0 microgram/l. in 1980 was associated with a 20-fold excess risk of cancer between 1981 and 1986, and an 8-fold risk between 1987 and 1991. Conclusions Diagnosis of clinically significant prostate cancer can be advanced substantially by serum PSA testing. However, the large number of high serum PSA values in men who remained free of clinical disease emphasizes the need for a more specific screening test.

Urinary Prostate Specific Antigen Levels: Role in Monitoring the Response of Prostate Cancer to Therapy

We have shown that prostate specific antigen (PSA) levels can be as readily obtained from voided urine as from serum samples. This procedure was found to give stable and reproducible results. PSA analyses were performed on voided urine collected from 42 patients with benign prostatic hypertrophy (BPH), 27 with stage D2 prostate cancer and 57 after radical prostatectomy. The 42 BPH samples had a mean urinary PSA level of 216ng./ml., which did not correlate with estimated prostate size. For 4 of 5 patients with stage D2 disease who presented before hormonal therapy urinary PSA levels were greater than 50ng./ml. For 22 stage D2 patients seen after initiation of hormonal therapy the majority had low urinary PSA levels. After initiation of hormonal therapy in most cases low urinary PSA levels were found in conjunction with high serum PSA values. However, in other cases we found high urinary PSA with low serum PSA levels. Of 43 patients who underwent radical prostatectomy for stages A to C disease it was noteworthy that 77% had elevated urinary PSA levels, while only 33% had elevated serum levels. Therefore, close to 80% of these patients have prostate tissue remaining locally after this operation.

Prostate-Specific Antigen (PSA) in the Management of 500 Prostatic Patients

Blood samples from 500 patients with clinical prostatic symptoms were radioimmunoassayed with prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) kits. On the basis of histological data, directed by PSA results and other investigations, 200 prostatic cancers (adenocarcinomas), 276 benign prostatic hypertrophy (BPH), 16 cases of prostatitis, 5 cancers of the bladder, and 3 prostatodynias were diagnosed. All of the serum samples from prostatic cancer patients showed elevated PSA levels at diagnosis, whereas about 70% of these showed normal PAP values. The sensitivity of the PSA assay is 100% when 2.5 ng/ml is taken as the upper limit of normal. However, the specificity and the positive predictive value are better at 10 ng/ml: 99 and 79%, respectively. High PSA values alerted the clinician when diagnosing a cancer without symptoms on rectal or ultrasonographic examination (3%). In BPH, when the PSA level is between 2.5 and 10 ng/ml, a PSA control must be performed within 2 months. If PSA increases above 10 ng/ml, the risk of cancer has to be considered. In the follow-up, PSA is a better marker than PAP to detect disease progression and seems to constitute an evolutive tumor mass index. PSA is the most sensitive, the earliest, and the most prognostically reliable marker for diagnosis and follow-up of prostate cancer patients.