Normal Prostate-specific Antigen Levels Research Articles

Diagnosis of Prostatic Carcinoma: The Yield of Serum Prostate Specific Antigen, Digital Rectal Examination and Transrectal Ultrasonography

Three tests are commonly used to diagnose prostate carcinoma to date: serum prostate specific antigen (PSA), digital rectal examination and transrectal ultrasonography. We evaluated these 3 tests in 1,001, 6-sector prostate needle biopsies to rule out prostate carcinoma. Of the biopsies 253 (25.3%) revealed prostate cancer. As a single test, PSA was superior to digital rectal examination or transrectal ultrasonography in predicting cancer in this patient population using difference of proportions tests. Receiver operating characteristic analysis also showed PSA to be the superior test. The combinations of PSA plus transrectal ultrasonography and PSA plus digital rectal examination were superior to digital rectal examination plus transrectal ultrasonography. We found cancer in 35 of 188 patients (18.6%) with intermediate PSA levels of 4.1 to 10.0 ng./ml. and normal or asymmetric nonindurated rectal examinations. Only 5 of 79 patients (6.3%) with a normal digital rectal examination and PSA level of less than 4.0 ng./ml. demonstrated carcinoma on biopsy. Of the 5 patients 4 had annual increases in PSA of 40% or greater. While hypoechoic sectors were more than twice as likely as isoechoic sectors of the prostate to contain malignancy on biopsy, nearly 37.6% of the cancers were found in isoechoic sectors. A strategy of performing biopsy of only hypoechoic sectors would have misdiagnosed 24.6% of the patients with prostate cancer. We conclude that serum PSA is the most accurate of the 3 diagnostic tests evaluated. We also recommend a systematic sextant biopsy technique.

Prostate-specific antigen and digital rectal examination in screening for prostate cancer: a community-based study.

In this study, 1,027 healthy men over age 40 were screened for prostate cancer with digital rectal examinations (DRE) and prostate-specific antigen (PSA) levels. Findings were abnormal in 189 (18%). PSA levels alone were abnormal (> 4.0 ng/mL) in 111 men (12%), 60 men (8%) had abnormal DRE and normal PSA, and 18 men had abnormal results of both examinations. Of the 189 men, 176 (93%) were referred for follow-up studies, and 39 cases of prostate cancer were detected. Of the 60 men with abnormal findings on DRE and normal PSA levels, only 2 men (3%) were found to have prostate cancer. Twenty-two of the 107 men (21%) with PSA levels between 4.0 and 9.9 ng/mL and 14 of 22 men (64%) with a PSA level greater than 10 ng/mL had prostate cancer. Conversely, 36 of the 39 men (92%) with prostate cancer had a PSA level greater than 4.0 ng/mL. Of 18 men with both abnormal DRE and elevated PSA, 9 (50%) were found to have prostate cancer. Overall, the 39 men found to have prostate cancer constituted 3.8% of the population screened; 25 of them (64%) had disease clinically confined to the prostate. PSA in combination with DRE appears to be useful in detecting prostate cancer in its early stages. Prospective randomized trials must be completed to determine whether early detection will have an impact on overall mortality from prostate cancer.

Clinical Significance of Prostate Specific Antigen for Early Stage Prostate Cancer Detection

The characteristics of serum prostate specific antigen (PSA) in normal Japanese men were studied in 1480 subjects examined by mass screening (MS) for prostate cancer (Pca) in Gunma Prefecture in 1992. The serum PSA concentration was correlated with patient age. The average serum PSA level increased by 0.04 ng/ml/year. The upper normal limits (95 percentiles) of age specific PSA for normal men are 1.33 ng/ml for those aged 39-49 years, 3.65 ng/ml for those aged 50-59 years, 4.06 ng/ml for those aged 60-69 years, 5.09 ng/ml for those aged 70-79 years and 5.66 ng/ml for those aged 80-89 years. Among 227 normal men examined by our MS in 1991 and 1992, the PSA velocity (PSAV) was calculated to be 0.05 ng/ml/year. Among 10 Pca patients with normal PSA levels (< 6 ng/ml) detected previously by our MS, three had an abnormal PSAV. We demonstrated the possibility that PSA density could distinguish between Pca and benign prostate hypertrophy. The significance of PSA as a Pca screening modality should be evaluated across multiple age ranges and in combination with previous PSA data and/or prostate volume estimated by sonography.

Correlation of serum prostate specific antigen levels and bone scintigraphy in carcinoma prostate.

Serum prostate specific antigen (PSA) has been suggested as an accurate means of monitoring prostate cancer. An analysis of PSA levels and bone scan findings was carried out in a heterogeneous group of patients with a view to determine whether PSA can accurately predict bone metastases in carcinoma prostate. Of the 48 patients studied, all 10 untreated cases had elevated PSA levels, eight having bone metastases. In 29 cases on follow-up after treatment of the primary, 10 out of 11 cases with normal PSA had a negative bone scan. In the nine who received hormonal therapy, the PSA levels were generally lower than others in the study group. Two out of four with normal PSA had bone metastases. In 26 cases with positive bone scans, 23 had elevated PSA levels (mean 109.9 ng ml-1). Among 22 patients who had normal bone scans, all 10 with high PSA were found to have soft tissue disease which could explain the elevated PSA. In those with normal PSA, 12 out of 15 patients had negative scans. PSA has fairly high sensitivity (86.5%) and negative predictive value (80%). But it suffers from low specificity (54.5%) and low positive predictive value (69.7%) for bone metastases. In an untreated patient with elevated PSA, a bone scan may be required to exclude bone metastases, whereas during follow-up after treatment, a normal PSA level may obviate a "routine" bone scan.

Clinical and US findings in prostate cancer: patients with normal prostate-specific antigen levels.

To determine guidelines for biopsy in men with normal prostate-specific antigen (PSA) levels and suspected prostate cancer. The clinical-sonographic features of 91 lesions of reduced echogenicity in 83 men with normal PSA levels who underwent transrectal ultrasound-guided biopsy were analyzed. Sixteen men (19%) had cancer, two with bilateral foci, and four had prostatic intraepithelial neoplasia (PIN). Fourteen of 47 discrete hypoechoic lesions yielded cancer or PIN versus only five of 44 ill-defined vaguely hypoechoic lesions (P = .03). Fifteen of 18 malignant lesions exceeded 1 cm in longest dimension. In 47 men, sonographic and digital rectal examination (DRE) findings corresponded; 17 (36%) had cancer or PIN. By contrast, of 36 patients with differing sonographic and DRE findings, only three (8%) had malignancy at biopsy (P < .01). Predictors of malignancy at sonography of the peripheral prostate gland in men with normal PSA levels include (a) lesion size, (b) degree and focality of hypoechogenicity, and (c) correspondence with the site of DRE abnormality.

Re-evaluation of the need for pelvic lymphadenectomy in low grade prostate cancer.

In a series of 166 patients undergoing radical prostatectomy and bilateral pelvic lymph node dissection for clinical stage A and B prostate cancer we found that 83% of patients with lymph node metastases had a final tumour Gleason score > or = 7. Gleason scoring of the pre-operative biopsy demonstrated 3 groups of patients with biopsy scores < or = 5, 6, and > or = 7, and a prevalence of lymph node metastases of 2, 13 and 23% respectively. The pre-operative serum prostate specific antigen (PSA) was of marginal value in predicting either the presence of lymph node metastases or the presence of cancer, since 15% of patients with nodal metastases had normal pre-operative PSA levels, as did 54% of patients with tumour Gleason scores < or = 5. It was concluded that the need for pelvic lymph node dissection in patients with low grade tumours is questionable because of the low prevalence of lymph node metastases, and that the pre-operative biopsy can identify those patients who are at low risk for lymph node metastases.

Prostate-specific antigen to determine progression-free survival after radiation therapy for localized carcinoma of prostate

Prostate-specific antigen (PSA) levels after radiation therapy will more precisely and objectively identify the presence of persistent prostate carcinoma. We determined the impact of PSA marker levels on progression-free status for 123 patients treated by interstitial implantation (I-125) and 311 patients treated by external beam therapy (XRT) who have been followed for a median of 109 and 51 months, respectively. Actuarial progression-free survival curves were calculated, using standard clinical criteria, and then recalculated, using PSA marker criteria. Sera obtained twelve months or more after the initiation of XRT and twenty-four months or more after the date of I-125 were used for determination of PSA levels. Using normal PSA level (by Hybritech assay ≤ 4.0 ng/mL) as the criterion for progression-free status for patients treated by XRT, 35 percent of patients with Stage A2, 20 percent of patients with Stage B1 or B2, and 10 percent of patients with Stage C tumor were progression-free at ten years. The progression-free survival by clinical criteria for Stage A2 was 65 percent, B 1 was 40 percent, B2 was 35 percent, and C was 25 percent. Using undetectable PSA level (≤ 0.5 ng/mL) as the criterion, less than 10 percent of patients were progression-free at ten years, regardless of stage, grade; and treatment modality. This information should not be interpreted as indicating that radiation is ineffective therapy for prostate cancer, since clinical control of the disease among men in their eighth decade is a more practical goal than marker control. However, PSA monitoring after radiation therapy and after any local therapy for prostate cancer will provide more precise information on the success of that therapy in ablating disease.

Can prostate specific antigen predict bone metastases?

The aim of our study was to determine whether a normal or raised Prostate Specific Antigen (PSA) level could negate the need for a bone scan in the staging or post-therapeutic follow-up of carcinoma of the prostate. A retrospective study was made of 759 consecutive patients who had had PSA levels assayed in our laboratory. We selected the 147 patients in whom a bone scan investigation was performed within one month of the PSA level determination. Patients were grouped according to PSA concentrations and the likelihood of metastatic disease on bone scan. Results as shown: PSA(μg/I)nBone Scan ReportNormal or Intermediate(%)Insignificant or significant(%)0 - 45343(81)10(19)4-101717(100)0(0)10-502815(53)13(47)>50497(14)42(86)Total14782(56)65(44) PSA levels are dependent on androgens¹. When exclusions were made for patients being followed-up after anti-testosterone intervention, 7 patients (14%) with a normal PSA level and prostatic carcinoma had an intermediate or significant bone scan report. Prostatic acid phosphatase was found to be of no additional value to PSA in predicting bone scan findings. Our results show that while PSA levels tend to correlate with bone scan findings, it cannot be used with certainty to predict bone scan findings and hence abrogate the need for a bone scan. 1Bilhartz DL, Young CYF, Flanagan WF, He W, Tindall DJ. Androgen regulation of prostate specific antigen (PSA) in human prostate carcinoma. (Abstract) J Urol 1990; 143: 203A

Prostate Specific Antigen in the Management of Patients with Localized Adenocarcinoma of the Prostate Treated with Primary Radiation Therapy

The records of 143 patients treated at 5 institutions with external beam megavoltage irradiation for localized prostatic cancer were reviewed to evaluate post-treatment changes in prostate specific antigen (PSA) in the context of subsequent events. Complete responders were defined as patients clinically well with normal PSA, clinical failures were patients with documented local tumor recurrence or distant metastases and chemical failures were patients clinically well but with a PSA level above the upper limits of normal. Correlations with pre-treatment PSA values were also made for the 50 of 143 patients for whom pre-treatment PSA data were available. Median patient followup was 27 months (range 18 to 91 months). The data were analyzed with parametric and nonparametric univariate and multivariate statistical procedures.Pre-treatment PSA levels increased with increasing tumor stage (p = 0.004) but not with increasing summed Gleason pattern scores (p = 0.15). The probability of remaining a complete responder decreased with increasing stage (p = 0.008) but not with increasing Gleason score (p = 0.14). Increasing pre-treatment PSA correlated with clinical failure (p = 0.01) and chemical failure (p = 0.006). Of the patients with a pre-treatment PSA level of less than 4 times the upper limits of normal 83% remained as complete responders compared to 30% of those with a higher pre-treatment PSA (p = 0.0002). The return of PSA levels to the normal range within 6 months after treatment was strongly correlated with a favorable outcome when analyzed by multivariate logistic regression. The status at last followup of patients who had a normal PSA level at 6 months versus those with an elevated PSA level 6 months after treatment is 94% versus 8% for complete responders (p = 0.0001), 0% versus 60% for clinical failures (p = 0.002) and 6% versus 32% for chemical failures (p = 0.14). Similar results occurred when analyzing outcomes in relationship to PSA normalization within 12 months after treatment (p = 0.001 for clinical failures, p = 0.02 for chemical failures and p = 0.001 for complete responders). We conclude that the pre-treatment level of PSA is an independent prognostic factor for prostate cancer patients treated with primary radiation therapy, and that the failure of PSA to return to the normal range within 1 year after completion of treatment identifies a group of patients at high risk for tumor recurrence.

Prostate Specific Antigen and Local Recurrence after Radical Prostatectomy

We evaluated the location of recurrent disease in 63 patients with carcinoma of the prostate who had abnormal levels of prostate specific antigen (>0.4ng./ml., Tandem-R† assay) 6 to 240 months after radical prostatectomy but who were otherwise considered to be without evidence of disease. The evaluation involved physical examination including digital rectal examinations by 3 urologists, isotopic bone scans, computerized tomography scans of the abdomen and pelvis, cystoscopy, and random needle biopsies of the urethrovesical anastomotic area. In 6 patients metastatic disease to the bone and/or lymph nodes was found and local prostate cancer was discovered in 5. Among 57 patients without evidence of disease by the usual methods of evaluation needle biopsies of the anastomosis revealed local disease in 42%. No local disease was discovered in 30 post-radical prostatectomy patients with normal prostate specific antigen levels. There was a wide range of transrectally palpable contours after radical prostatectomy in patients with and without elevated prostate specific antigen levels. We conclude that prostate specific antigen but not digital rectal examination is an excellent early indicator of possible local recurrence after radical prostatectomy. Whether the prevalence of local disease after radical prostatectomy using prostate specific antigen levels and needle biopsies of the anastomosis is greater than heretofore has been appreciated will require further study. (J. Urol., 144: 921–926, 1990)