Prostate-specific antigen as a marker of adenocarcinoma of prostate

Summary Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) serum levels were measured in 117 patients with prostatic adenocarcinoma, in 9 patients with prostatic hyperplasia and in 14 patients with other malignancies to compare the clinical usefulness of the PSA and PAP levels. PSA was elevated (PSA⁺) in 14 of 18 untreated patients (78%) with prostatic cancer. PAP was elevated (PAP⁺) only in 3 of these untreated cases (17%). Also in previously treated patients PSA was more often positive than PAP. PSA was positive in 40 of the 99 treated patients (40%), PAP was elevated only in 21 cases (21%). There was a significantly (P<0.001) higher tendency towards elevated PSA in the prostatic cancer patients: 32 (27%) patients with PSA⁺ and PAP^- compared with only 2 cases (2%) with PAP⁺ and PSA^-. The PSA⁺/PAP^- patients were analyzed further. In seven of them the PSA level also returned to its normal level after orchiectomy or/and radiotherapy. In two patients the PSA levels indicated tumor progression earlier than PAP, their PAP levels did not rise until bone metastasizing was evident. There were also progressive disease in some patients evidenced only by increased PSA levels. In addition to cancer patients the PSA level was increased in three (30%) of the prostatic hyperplasia patients. It was also elevated in three patients with other malignancies. However, these three patients also had prostatic hyperplasia and the increase in the PSA level is considered more likely to be due to that. According to these findings it is suggested that PSA is more sensitive than PAP in local and advanced prostatic cancer and may be more useful in monitoring responses and recurrence after therapy.     

Comparison of prostate secretory protein with prostate specific antigen and prostatic acid phosphatase as a serum biomarker for diagnosis and monitoring patients with prostate carcinoma

Serum prostate secretory protein (PSP) levels were measured in 49 patients with benign prostatic hyperplasia (BPH), 144 patients with various stages of prostatic carcinoma (CaP), and 82 CaP patients who were followed serially. PSP values were compared with serum levels of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). In the BPH group, PSP was elevated (> 10 ng/ml) in 41% of patients, whereas PSA (> 4 ng/ml) and PAP (> 3.3 ng/ml) were elevated in 39% and 23% of the cases, respectively. PSP levels were elevated in 48% of the CaP pretreatment specimens, compared to 79% for PSA and 40% for PAP. PSP levels in cancer patients who had intracapsular disease were about two to three times higher than those observed for PAP. PSP was found to be the only marker elevated in eight (6%) pretreatment CaP patient serum specimens, while PAP was never found to be elevated when PSA was normal. PSP serum concentrations correlated with the clinical course of the disease in 79% of patients, compared with 90% for PSA and 66% for PAP. In certain patients, monitored over time, disease correlation was reflected in serum values with only a single biomarker, i.e., 1% with PAP, 8% with PSP, and 10% with PSA. This study has shown that PSP is a less sensitive serum biomarker than PSA, but more sensitive than PAP for detection and monitoring the early stages of prostate cancer. This suggests that PSP as a biomarker may be a useful adjunct for the management of a subpopulation of low-stage and -grade CaP. © 1993 Wilcy-Liss, Inc.     

The significance of serum gamma-seminoprotein in prostatic cancer

The level of serum gamma-seminoprotein (gamma-Sm) was determined by enzyme immunoassay using an EIA gamma-Sm test kit in 32 patients with prostatic cancer (before treatment for 12 and after treatment was started for 20), 24 patients with benign prostate hypertrophy and 22 patients with other urogenital cancer. A gamma-Sm level of over 4.0 ng/ml was considered to be positive. The positive rate was 43.8% in prostatic cancer patients (83.3% before and 20.0% after treatment), 25.0% in benign prostate hypertrophy and 0% in other urogenital cancer. Since the positive rate of prostatic acid phosphatase (PAP) was 34.3% in prostatic cancer patients (75.0% before and 10.0% after treatment) and 16.7% in benign prostate hypertrophy patients, gamma-Sm may be more sensitive but less specific as an indicator of prostatic cancer in PAP. In 9 patients with prostatic cancer before treatment, the levels of serum gamma-Sm and PAP were serially determined for up to 11 months. The level of gamma-Sm decreased in 7 patients, and PAP in all patients after hormone therapy. One patient showed a consistently positive gamma-Sm level and the level of the others became positive only for gamma-Sm during follow-up. There was a statistical correlation between the levels of serum gamma-Sm and PAP in patients with prostatic cancer (r = 0.595, p less than 0.01), in patients with benign prostate hypertrophy (r = 0.882, p less than 0.01) and also in the patients in both groups together (r = 0.590, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of prostate-specific antigen in untreated prostatic carcinoma

A study was performed on 290 men to compare the level of serum prostate-specific antigen (PSA) in controls, patients with benign prostatic hyperplasia (BPH) and patients with prostatic cancer. The upper limit of normal was 5.0 micrograms/l as determined in 110 elderly hospitalized males (mean age 62 years) without urological complaints. Of the 106 patients with BPH, 33% had raised values above 5.0 micrograms/l. Values above 10 micrograms/l were found in 18 BPH patients. A positive correlation was found between prostate volume (grams of tissue removed during transurethral resection) and preoperative PSA levels (r = 0.55, n = 106, p less than 0.001). PSA levels above 10 micrograms/l were found in 4% of BPH patients with a prostate volume of less than 20 g (n = 54), in contrast with 45% of patients with a prostate volume above 40 g (n = 20). The sensitivity of this PSA assay (cutoff level 10 micrograms/l) as established in 74 prostate carcinoma patients was 31% for category T0 (n = 13), 56% for category T1-2 (n = 16), 75% for category T3-4 (n = 20) and 100% for category M1 or N1-4 (n = 25). In an earlier study prostatic acid phosphatase (PAP) was measured in these same samples. PSA appeared to be much more sensitive than PAP. Seventeen of the 74 prostatic carcinoma patients (23%) had normal PAP levels but their PSA values were raised above 10 micrograms/l, while in only 2 patients an increased PAP level was combined with a normal PSA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prediction of pelvic lymph node metastases by a prostate-specific antigen and prostatic acid phosphatase in clinical T3/T4M0 prostatic cancer.

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) were determined in the serum of 69 patients with clinical T3/T4M0 prostatic cancer before staging lymphadenectomy. In principle, high-dose radiotherapy was given only to patients of pathological N0 category. Seventeen patients had a prelymphadenectomy PSA level below the normal upper reference limit (10 micrograms/l) and only 3 of them had pelvic lymph node metastases. Fifteen of 52 patients with a preoperative PSA level > or = 10 micrograms/l were of N0 category. Only 8 of the 41 evaluable patients had PAP values above the normal range, and 6 of these 8 patients had pelvic lymph node metastases. Preoperative PSA values, but not preoperative PAP levels, assist the clinician in predicting regional lymph node metastases in patients with clinical T3/T4M0 prostatic cancer. Two-thirds of the patients with T3/T4 tumours and PSA values between 10 and 50 micrograms/l have regional lymph node metastases. About 80% of the patients with PSA levels < 10 micrograms/l belong to the N0 category. About 75% of the patients with PSA > 50 micrograms/l have N+ disease. Taking into account the individual preoperative PSA values, the indication for preradiotherapy staging lymphadenectomy should be balanced between the chance of demonstrating N+ disease, the expected postoperative morbidity and the benefit for the patient found to be of N0 category.     

Evaluation of prostate-specific antigen and prosttic acid phosphatase as prostate cancer markers

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) have been evaluated in patients with prostate cancer, benign prostatic hypertrophy (BPH), and prostatitis. PSA has proved to be diagnostically more sensitive than PAP for the detection of prostate cancer: 95.0 per cent vs 60.0 per cent for 40 newly diagnosed cancer cases, and 97.1 per cent vs 65.7 per cent for 35 relapsed cases. This also holds true for those patients with early-stage disease: 71.4 per cent vs 0 per cent for 7 Stage A1 cases. The specificities of PSA and PAP are comparable, 96.8 per cent vs 98.9 per cent, respectively. PSA is also more sensitive for monitoring therapy, since it usually rises before PAP and always precedes clinical signs of relapse. Although PSA may be elevated more frequently than PAP in some patients with BPH and prostatitis, it is postulated that these patients with elevated serum PSA and normal serum PAP may fall into a high-risk sub-population which may have early prostate cancer or precancerous conditions not easily detectable by current clinical and diagnostic techniques. Our data suggest PSA is a sensitive useful tumor marker for the diagnosis and management of prostate cancer. In addition, PAP, in combination with PSA, may serve as a useful adjunct for differential diagnosis and confirmation of advanced stage prostate cancer.     

Evaluation of prostate-specific antigen and prostatic acid phosphatase as prostate cancer markers

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) have been evaluated in patients with prostate cancer, benign prostatic hypertrophy (BPH), and prostatitis. PSA has proved to be diagnostically more sensitive than PAP for the detection of prostate cancer: 95.0 per cent vs 60.0 per cent for 40 newly diagnosed cancer cases, and 97.1 per cent vs 65.7 per cent for 35 relapsed cases. This also holds true for those patients with early-stage disease: 71.4 per cent vs 0 per cent for 7 Stage A1 cases. The specificities of PSA and PAP are comparable, 96.8 per cent vs 98.9 per cent, respectively. PSA is also more sensitive for monitoring therapy, since it usually rises before PAP and always precedes clinical signs of relapse. Although PSA may be elevated more frequently than PAP in some patients with BPH and prostatitis, it is postulated that these patients with elevated serum PSA and normal serum PAP may fall into a high-risk sub-population which may have early prostate cancer or precancerous conditions not easily detectable by current clinical and diagnostic techniques. Our data suggest PSA is a sensitive useful tumor marker for the diagnosis and management of prostate cancer. In addition, PAP, in combination with PSA, may serve as a useful adjunct for differential diagnosis and confirmation of advanced stage prostate cancer.     

Efficacy and discriminative ability of prostate-specific antigen as a tumor marker.

A study was performed on 175 men to compare the level of prostate-specific antigen (PSA) in patients with benign prostatic hyperplasia (n = 83) and prostatic carcinoma (n = 92). There was a good correlation between T stage and increasing values of PSA. Using 2.5 ng/ml as the upper normal limit of PSA, the test sensitivity of PSA was 94%, but the specificity only 44%. Receiver-operator characteristic curve (ROC) analysis demonstrates that PSA is superior to prostatic acid phosphatase (PAP); this is particularly true in the higher T stages. Although ROC analysis shows that PSA is more discriminating than PAP, the sensitivity of PSA is dependent upon the choice of an appropriate cut-off point of the test. It was shown that PSA is not sufficient for detecting the presence or absence of prostatic cancer in a general population. However, PSA is the most sensitive marker in the detection of prostatic cancer.     

Clinical evaluation of a prostate-specific antigen as a serum marker of prostatic cancer

Combined measurement of serum prostate-specific antigen (PA) and prostatic acid phosphatase (PAP) was performed in 235 patients with various urologic diseases including 55 patients with prostatic cancer. A PA level of over 24.7 ng/ml and a PAP level of over 3.1 ng/ml were considered to be positive. The positive rate of PA was 57% in the patients with untreated prostatic cancer and 3% in the patients without prostatic cancer. The positive rate of PAP was 52% in the patients with untreated prostatic cancer and 1% in the patients without prostatic cancer. PA and PAP were considered to be equally sensitive and specific serum markers of prostatic cancer. However, the positive rate increased to 65% without increasing the false positive rate when the PA and PAP were both measured simultaneously. The combined assay of PA and PAP is recommended for screening prostatic cancer. The cross-over titer of PA and gamma-Sm using standard samples in each kit revealed linearity, which suggested that PA and gamma-Sm possess the same antigenicity.     

Clinical evaluation of serum basic fetoprotein for prostatic cancer--comparative study with PAP, gamma-Sm and PSA]

The clinical significance of serum basic fetoprotein (BFP) in prostatic cancer was investigated together with serum prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostate specific antigen (PA). Investigated in this study were 40 patients with prostatic cancer, ranging in age from 50 to 85 years (mean age: 69.5 years). According to clinical staging, 3 cases (7.5%) had a stage A disease, 10 cases (25.0%) a stage B disease, 7 cases (17.5%) a stage C disease, and 20 cases (50.0%) a stage D disease. The positive rates for serum BFP, PAP, gamma-Sm, and PSA were 60.0, 45.0, 63.6, and 68.4%, respectively, and these rates increased as the stage advanced. The above results suggest that BFP is the most useful marker of the four for monitoring prostatic cancer. In a combination assay of these four markers, 29 (87.9%) of 33 patients with prostatic cancer could be diagnosed by observing an elevated serum level in one of the markers. This suggests that a combination assay of BFP, PAP, gamma-Sm and PSA in patients with prostatic cancer is useful for diagnosis and monitoring of the disease.     

PROSTATE-SPECIFIC ANTIGEN IN MASS SCREENING FOR CARCINOMA OF THE PROSTATE

Background:
Prostate-specific antigen (PSA) has various advantages over prostatic acid phosphatase (PAP) as a marker for prostate cancer, but its role in prostate cancer mass screening remains controversial. We measured serum PSA in addition to serum PAP determination and digital rectal examination (DRE) in our mass screening program to assess the usefulness of PSA for prostate cancer mass screening.
Methods:
Serum PSA and PAP measurements and DRE were performed in 1249 patients in mass screening for carcinoma of the prostate in 1989 and 1990. Thirteen cancers were diagnosed. We calculated the mean plus standard deviations (2SD) of the PSA and PAP values of men without cancer, and assessed the usefulness of PSA for prostate cancer screening by using these figures as the upper limit of normal.
Results:
The number positive for PSA, PAP and DRE were 39, 36 and 48, respectively. If our screening had been performed without DRE, three cancers would have remained undetected, and the number would have been the same if performed without PSA. If the screening had been performed without PAP, on the other hand, no cancers would have remained undetected. The sensitivities of PSA and PAP were 54% and 23%, respectively. The screening detection rate with DRE and PSA was 0.88%, and with DRE and PAP was 0.64%.
Conclusions:
Measurement of serum PSA values with adjustment of the cut-off value was considered more useful than PAP in mass screening for prostate cancer.     

Excretion of three major prostatic secretory proteins in the urine of normal men and patients with benign prostatic hypertrophy or prostate cancer

We have studied the mode of excretion of three prostatic secretory proteins, namely acid phosphatase (PAP), prostate-specific antigen (PSA) and beta-inhibin, in the urine of normal adult men, and we have determined the urinary levels of these proteins in men with benign prostatic hypertrophy (BPH) or adenocarcinoma. The output of the three proteins was highly variable during the day. In order to minimize these variations, 24-hour urine samples were collected thereafter. Our study showed that PAP concentrations in 50% of men with or without symptomatic BPH were similar to those of normal young men. In the remaining 50%, PAP was undetectable. In contrast, average PSA and beta-inhibin concentrations were higher in patients with BPH than in young men (p less than 0.05). The three markers were decreased or nondetectable in about half of the patients with untreated prostatic cancer. This phenomenon was even more pronounced in patients receiving hormonal treatment (castration or diethylstilbestrol). However, some of these patients still excreted normal amounts of PAP, PSA, and beta-inhibin. Urinary and serum PAP levels showed no correlation. These results indicate that urinary prostatic markers provide an easy means to study the behavior of the primary prostatic tumor. This information may be of potential value since it is not obtained with serum markers which originate mostly from metastatic cells.     

Tumour markers in prostatic carcinoma. A comparison of prostate-specific antigen with acid phosphatase

A study was performed on 130 men to compare the level of serum prostate-specific antigen (PSA) in controls, patients with benign prostatic hyperplasia (BPH) and patients with prostatic carcinoma. The results showed that all 30 normal controls below 40 years of age had values less than 10 ng/ml. Of the 40 patients with BPH, all aged over 40 years, 13 (32.5%) had raised levels above 10 ng/ml. In the 60 patients with prostatic carcinoma, all over 40 years, 24 had localised disease (MO) and 36 had metastatic spread (M1), as judged by isotope bone scan. In patients with MO disease, 16 (66.6%) had raised PSA levels compared with 34 (94.5%) of those with M1 disease. The corresponding figures for raised prostatic acid phosphatase (PAP) values were 4% in the MO group and 52.7% in the M1 group. PSA levels reflected neither the histological grade nor the local stage of the tumour and were of no value in estimating tumour burden. PSA was found to be a valuable index in the management of prostatic cancer because of this sensitivity. Stable disease not requiring hormonal manipulation was reflected by unchanging levels of PSA, whereas progressive disease requiring hormonal therapy was reflected by an alteration in the PSA levels corresponding to the patients' response. The same group of progressive disease patients showed only a 50% rise in serum PAP levels, confirming the greater sensitivity of PSA as a measure of prostate cancer. PSA measurements should be included in any further trials on prostatic carcinoma and should be regarded as a standard marker for evaluating response to therapy.     

Daily variability in human serum prostate-specific antigen and prostatic acid phosphatase: a comparative evaluation

The daily variation of serum levels of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) was investigated simultaneously in 10 patients with osseous metastatic prostatic cancer, 10 patients with benign prostatic hyperplasia, and 10 volunteers without prostatic disease. Duplicate serum samples were obtained from all patients on the same day at 8 AM, 12 PM, 4 PM, and 8 PM. Statistical analysis (two-factor analysis of variance comparing time period to disease group) of the mean PSA and PAP levels at the four sampling times on all patient groups demonstrated no evidence of circadian rhythmic variation or any other distinct pattern for the observed sample times. Overall, the variability in PSA levels was significantly less than that observed for PAP. There was no significant difference in mean percent variation between patient groups (cancer, benign, and normal prostate glands) for both the PSA and PAP assays. Our data reveal that serum PSA measurements fluctuate unpredictably over the course of a day in patients with and without prostatic disease, but to a lesser extent than that seen for serum PAP values. These findings illustrate the potential inaccuracy of single determinations of serum PAP or PSA levels for monitoring disease recurrence and treatment response in patients with prostate cancer.     

Contribution of bone scintigraphy, prostatic acid phosphatase and prostate-specific antigen to the monitoring of prostatic cancer

Changes in the serial measurements of serum prostatic acid phosphatase (PAP), and prostatic specific antigen (PSA) have been compared against changes in serial bone scans in 120 patients with prostatic cancer. Of 54 patients who presented with negative bone scans 10 developed skeletal metastases, the PAP and PSA levels were rising in 5 and 9 of these patients, respectively. Local progression occurred in a further 9 patients in whom PAP was rising in 8 and PSA in all 9. In the 66 patients with previously documented skeletal metastases bone scan evidence of progression was seen in 36. At the time of the first evidence of progression PAP was rising in 20 (55%) and PSA was rising in 26 (72%). In 4 patients neither marker was raised at the time of first evidence of progression. We discuss the value of 'routine' serial bone scintigraphy in monitoring patients with prostatic cancer.     

Prostate specific antigen--a screening test for prostatic cancer?

A series of 287 patients referred by their family doctors with symptoms of bladder outflow obstruction were asked to attend the hospital for "pre-clinic" screening for carcinoma of prostate (CaP). Blood samples were collected from 211 patients and analysed for serum prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). Thirty-six patients had a serum PSA greater than 10 micrograms/l and 7 had PAP levels greater than 5 iu/l. In no instance was the PAP elevated without an associated increase in PSA concentration. Patients with raised markers underwent further investigations which included prostatic biopsy and/or resection; 17 patients were proved to have carcinoma of the prostate, 9 of whom had distant metastases. The specificity of PSA for detecting prostate cancer in this study was 90% with a sensitivity of 89.5%, in contrast to values for PAP of 100% and 36.8%. The routine use of PAP as a marker for prostatic cancer should be abandoned. The use of PSA as a screening test in a group of patients with prostatism appears justified, but with a positive predictive value of only 47%, its use in a mass unselected screening programme is not recommended.     

Comparative study of the clinical usefulness of prostate specific antigen and prostatic acid phosphatase in prostatic disease

The clinical usefulness of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) activity measurements has been compared in 45 patients with benign prostatic hyperplasia (BPH) and 132 patients with prostatic carcinoma (PC), 21 of whom had metastatic disease (MPC) and 111 of whom had intracapsular cancer. No BPH patient had increased PAP but 47% had increased PSA. Of the PC patients only 27% had increased PAP and 70% increased PSA. All of the MPC patients had increased PSA but only 62% had increased PAP. Increased PAP was found only in MPC but increased PSA was also found in BPH. In identifying PC, the predictive value of an increased PSA concentration is 83% and an increased PAP activity is 100%. On the other hand, the predictive value of a normal PSA concentration is 51% and of a normal PAP activity only 34%. As the PAP test is much less efficient than the PSA test, it should be discontinued.     

Serum prostate-specific antigen: hourly change/24 hours compared with prostatic acid phosphatase.

Simultaneous hourly changes in serum PSA and PAP levels per twenty-four-hour period was studied in 19 urologic patients with no prostatic disease. Serum PSA was determined using Hybritech PSA-R Kits, and PAP was determined using EIA method. PSA and PAP serum levels varied independently from each other. PSA level showed no diurnal variations. The level remained stable with minor variations around a low mean of 0.907 ng/mL, SD 0.09, and CV 9.9% in 16 of 19 (84%) patients, while PAP showed changes consistent with diurnal variations in 5 of those patients. Random variations with no discernible pattern in 7 and remained more or less constant in 4 other patients. Marked random variations in PSA serum level occurred in only 3 patients in the older age group and were accompanied by diurnal variations in PAP level in 2 patients and a constant high level of PAP in 1 patient. The highest PSA level obtained was 6.9 ng/mL which is important when selecting the cut-off level. PSA did not increase appreciably after prostatic massage, and on follow-up PSA returned to premassage level after twenty-four hours (except in 1 patient).     

PAP、PSA与前列腺癌的诊断

本院从1992年7月至1996年9月收治经病理检查证实的前列腺癌52例,均行直肠指检(DRE)、B超、血清前列腺酸性磷酸酶(PAP)和前列腺特异抗原(PSA)检查,其诊断前列腺癌阳性率分别为78.8％、50.0％、61.5％、84..％。PSA阳性率明显高于其它检查(P<0.005)。若结合DRE、TRUS则诊断前列腺癌之敏感性达到96.2％。经直肠前列腺穿刺活检31例,穿刺阳性率为87.1％。PAP、PSA升高患者的比例与前列腺癌的分期、肿瘤细胞分化程仅具相关性。因此,PAP、PSA对前列腺癌的诊断、临床分期、判断预后有较大价值。     

An evaluation of the immunochemical measurement of prostatic acid phosphatase and prostatic specific antigen in carcinoma of the prostate

Serum prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP) were evaluated with double monoclonal radioimmunoassays. In 250 patients with prostatic cancer the normal limits were as follows: PSA 0.1-2.7 ng/ml, and PAP 1.09 +/- 0.45 ng/ml (mean +/- SD). In 91 untreated patients with non-metastatic tumours, 42.8% had PSA greater than 10 ng/ml and 18.6% had PAP greater than 2 ng/ml. In 60 untreated patients with metastatic disease PSA was greater than 10 ng/ml in 91.7%; PAP was greater than 2 ng/ml in 65%. In prolonged remission PSA was generally less than 5 ng/ml and PAP less than 2 ng/ml. Longitudinal studies of 2-4 years showed the independence of these markers and a higher correlation of changes in the PSA level and clinical status than given by parallel PAP measurements. In non-metastatic disease, PSA greater than 10 ng/ml at presentation, with or without a coincidentally raised PAP, carried an increased risk of progression within 2 years.