Early stage prostatic cancer investigated by pelvic lymph node biopsy and bone marrow acid phosphatase

A prospective study was done to evaluate 47 patients with early stage prostatic cancer. Pelvic lymphadenectomy was combined with bone marrow acid phosphatase determination to evaluate early metastatic disease. Thirteen patients (28 per cent) had tumor in the pelvic lymph nodes. In no instance was the bone marrow acid phosphatase elevated to more than the normal value for serum by the substrate used. Combined high grade and stage tumors seemed to have an increased incidence of metastases to pelvic lymph nodes. A surprisingly high incidence of B1 lesions (5 of 21 patients or 24 per cent) had positive lymph nodes. Generally, the nodes were moderately well or well differentiated lesions. The metastases were unilateral, frequently microscopic only and involved 1 or only a few nodes. Pelvic lymphadenectomy seems to have a well defined role in the diagnostic study of early stage prostatic cancer, while bone marrow acid phosphatase determinations were of no value.     

Long-term cancer control after radical prostatectomy and bilateral pelvic lymph node dissection for pT3bN0M0 prostate cancer in the prostate-specific antigen era

ObjectivesWe evaluated long-term cancer control outcomes of radical prostatectomy and bilateral pelvic lymph node dissection (RP) for pT3bN0M0 prostate cancer in the era of prostate-specific antigen (PSA) screening.Materials and methodsA retrospective analysis of prospectively collected data from the University of Southern California Prostate Cancer Database was performed. Between 1987 and 2008, 229 men underwent open RP for pT3bN0M0 prostate cancer. The cohort was divided into early (1987–1997) and contemporary (1998–2008) PSA eras. The Kaplan-Meier method and Cox proportional regression models were used to analyze clinical recurrence (CR) and biochemical recurrence (BCR).ResultsThe median follow-up duration was 14.5 years (range, 0.2–21.1 y). The predicted 10-year freedom from CR and BCR rates for men treated in the early and contemporary PSA eras were 73% and 95% (Log-rank P = 0.001) and 65% and 73% (Log-rank P = 0.055), respectively. Multivariable analysis showed that pathologic Gleason grade 8–10 (CR: hazard ratio [HR] = 5.11; 95% confidence interval [CI] = 1.72–15.20; P = 0.003; BCR: HR = 3.47; 95% CI = 1.60–7.48; P = 0.002) and contemporary PSA era (CR: HR = 0.15; 95% CI = 0.06–0.41; P<0.001; BCR: HR = 0.49; 95% CI = 0.28–0.86; P = 0.013) were independently associated with cancer control. Adjuvant radiation therapy and positive surgical margins were not independently associated with outcomes.ConclusionsRP conferred long-term cancer control in men with pT3bN0M0 prostate cancer treated in the PSA era. Pathologic Gleason grade 8–10 and treatment in the early PSA era were independently associated with poorer cancer control outcomes.     

Value of prostate-specific antigen measurements in predicting lymph node involvement in prostatic cancer.

The preoperative serum levels of prostate-specific antigen (PA) were determined in 35 consecutive patients who had clinically localized prostatic cancer and underwent bilateral staging pelvic lymphadenectomy. When 10.0 ng/ml of PA was used as the cutoff value for lymph node staging the specificity of an elevated PA level in revealing lymph node involvement was 77% with a sensitivity of 85% and an accuracy of 80%. Only 1 of 18 (6%) patients with negative PA levels (below 10 ng/ml) and a preoperative Gleason score 2-7 tumor had metastatic lymph node disease. Among the 17 patients with positive PA levels (above 10 ng/ml) or a Gleason score 8-10 tumor, 12 (71%) had lymph node involvement. The preoperative PA level and the extent of local tumor invasion correlated strongly with each other. Our study suggests that the PA level could be a simple and objective parameter with which to predict metastatic lymph node disease if used in conjunction with the Gleason histological grade.     

Prostate-specific antigen and prostatic acid phosphatase in the detection of early prostate cancer and in the prediction of regional lymph node metastases.

Serum values of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) were determined in 180 patients prior to pelvic lymphadenectomy and radical prostatectomy and in 40 patients prior to pelvic lymphadenectomy alone. In all tumor stages, PSA was superior to PAP in detecting cancer of the prostate. By PSA determination using a cutoff level of 4 ng/ml (Tandem assay), 28.8% of the patients with prostate cancer, stage pT2pN0M0, and 17.8% of the cases with a stage pT3pN0M0 tumor could not be detected. All these tumors had been noticed, however, by digital rectal examination. This indicates that PSA determination cannot replace digital rectal examination as a screening method for prostate cancer. In this study, it was possible neither by PSA nor by PAP to define a practicable cutoff level for patients with and without lymph node metastases. A clear differentiation between the stages pT2pN0M0 and pT3pN0M0 was not possible by either PSA or PAP alone.     

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.     

Multiple marker evaluation in prostatic cancer with prostatic acid phosphatase, γ-seminoprotein and prostate-specific antigen

Serum prostatic acid phosphatase (PAP), γ-seminoprotein (γ-Sm), and prostate-specific antigen (PA) levels were measured in 63 untreated patients with prostatic cancer. The sensitivities of PAP, γ-Sm, and PA as markers of malignancy were 68%, 83%, and 77%, respectively. The latter two markers were more sensitive than PAP, especially in stage B disease. The specificities of PAP, γ-Sm, and PA were 95%, 93%, and 93%, respectively. Patients with multiple positive markers were very likely to have prostatic cancer. In reactivation of the disease, positive rates for γ-Sm and PA were higher than for PAP, indicating that the former two markers are more reliable for monitoring prostatic 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.     

Correlation between tissular levels of prostatic acid phosphatase and prostate-specific antigen and hormonal response of metastatic prostatic cancer

A correlation between the serum levels of testosterone and the tissular intensity of prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) in normal prostates has been demonstrated. In prostatic cancer patients, we studied the correlation between the percentage of neoplastic cells secreting PAP and PSA and the response to androgen deprivation, and found no relationship between them. Therefore it is not possible to predict the response to hormone therapy through the grade of tissular PAP or PSA.     

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).     

Prostate-specific antigen and prostate acid phosphatase in the detection of early prostate cancer and the prediction of regional lymph node metastases.

Serum values of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) were determined in 180 patients prior to pelvic lymphadenectomy and radical prostatectomy and in 40 patients prior to pelvic lymphadenectomy alone. In all tumor stages, PSA was superior to PAP in detecting cancer of the prostate. By PSA determination using a cutoff level of 4 ng/ml (Tandem assay), 28.8% of the patients with prostate cancer, stage pT2pN0M0, and 17.8% of the cases with a stage pT3pN0M0 tumor could not be detected. All these tumors had been noticed, however, by digital rectal examination. This indicates that PSA determination cannot replace digital rectal examination as a screening method for prostate cancer. In this study, it was possible neither by PSA nor by PAP to define a practicable cutoff level for patients with and without lymph node metastases. A clear differentiation between the stages pT2pN0M0 and pT3pN0M0 was not possible by either PSA or PAP alone.     

The immunohistochemical assessment of occult regional lymph node metastases in patients with T3pN0M0 prostate cancer before definitive radiotherapy

OBJECTIVE: To detect occult regional lymph node metastases in patients with T3pN0M0 prostate cancer not recognized by routine haematoxylin and eosin staining, and to evaluate the clinical relevance of this finding. PATIENTS AND METHODS: Formalin-fixed and paraffin-embedded pelvic lymph nodes (1118) from 92 patients were evaluated by immunohistochemistry using antibodies for prostate specific antigen (PSA) and pancytokeratin (AE1/AE3). Of the tumours, 14% were well, 69% moderately and 17% poorly differentiated. The extent of tumour was categorized as T3pN0M0 in all patients, who were referred for definitive radiotherapy after pelvic staging lymphadenectomy. The median (range) serum PSA value before treatment was 18.5 (0.4-342) microg/L. After radiotherapy, the patients were followed by assessing biochemical progression, pelvic recurrence and/or development of distant metastases. The median (range) observation time for all patients was 61 (16-136) months. RESULTS: Occult lymph node metastases were detected in four (4.4%) of the 92 patients. Patients with or without occult metastases had similar serum PSA levels and histological grades. None of the four patients with occult metastases progressed, compared with 37 of the 88 (42%) with no such metastases. CONCLUSION: Using immunohistochemistry the detection rate of occult lymph node metastases in patients with T3pN0M0 prostate cancer is low. The occurrence of such metastases is probably unrelated to the serum PSA value before treatment. The short-term outcome of patients subsequently treated with definitive radiotherapy does not seem to be associated with the finding of occult lymph node metastases, but long-term follow-up is needed. So far, the results do not justify the search for occult lymph node metastases as a routine procedure in these patients     

Urethral metastasis from prostatic carcinoma as diagnosed by immunoperoxidase technique using prostate-specific antigen and prostate-specific acid phosphatase

A rare case of urethral metastasis from prostatic adenocarcinoma is reported. Ordinary histological examination by hematoxylin and eosin staining could not determine whether the primary site was the prostate or the urethra. However, with an immunoperoxidase technique using prostate-specific acid phosphatase and prostate-specific antigen as markers for prostatic cells, we obtained a precise diagnosis of the primary sites. As a result, the patient could be successfully treated with hormonal therapy.     

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.     

The role of pelvic lymph node metastases in bladder cancer

Summary Among the 153 patients who had undergone cystectomy for primary bladder cancer, the expected deterioration of survival occurred as tumor stage advanced. Of 10 patients with either solitary, small resected intraabdominal metastases or involvement of the urethral margin, none survived longer than 3 years. Another 12 patients were found to have regional lymph node metastases; in 11 of these the positive nodes were located along the iliac or obturator vessels; these individuals also died within 3 years. The 12th patient, who had microscopic metastases in a lymph node from the perivesical fat, was alive with no evidence of disease at 42 months. Among the remaining 131 patients who had no evidence of lymphatic, intraperitoneal or distant metastases, nor tumor at the urethral margin, survival rates were not significantly different for the various pT categories. Our results suggest that patients with deeply invasive bladder carcinoma, but no evidence of extravesical spread (which becomes less likely the deeper the tumor infiltrates) have the same 5-year survival rate as patients with superficially invasive cancer of comparable grade. They also show that lymph node metastases along the pelvic wall portend an unfavorable outcome. However, those who have limited microscopic lymph node metastases, particularly if located in the perivesical fat, may expect a better prognosis as suggested by our patient and the reports in the literature.     

The significance of serum prostate-specific antigen, gamma-seminoprotein and prostatic acid phosphatase as prostate cancer markers

Prostate-specific antigen (PA), gamma-seminoprotein (gamma-Sm) and prostatic acid phosphatase (PAP) have been evaluated in patients with prostate cancer, benign prostatic hyperplasia (BPH), chronic prostatitis and acute prostatitis. PA has proved to be diagnostically more sensitive than PAP and gamma-Sm for the detection of prostatic cancer. Although PA may be elevated more frequently than PAP and gamma-Sm in patients with BPH, there are possibilities that these patients with elevated PA and normal PAP and gamma-Sm may have prostatic cancer or precancerous conditions not detectable in our routine diagnostic procedures. We report two cases of prostatic cancer with persistently elevated PA and diagnosed after repeated biopsies. Our data suggest that PA is a sensitive and useful tumor marker for the diagnosis of prostatic cancer. PAP and gamma-Sm in combination with PA may serve as more useful for differential diagnosis and confirmation of prostatic cancer.     

Suppression of LNCaP prostate cancer xenograft tumors by a prostate-specific protein tyrosine phosphatase,prostatic acid phosphatase

BACKGROUND: Although the molecular mechanism of androgen-independent prostate cancer growth and progression has been gradually elucidated, there is limited effective treatment for this prevalent disease. Human prostatic acid phosphatase (PAcP), a major protein tyrosine phosphatase in prostate epithelium, plays a critical role in regulating the growth of prostate cancer cells. In prostate carcinomas, the expression of cellular PAcP decreases. To explore directly the possible therapeutic potential of cellular PAcP, we investigated the suppression effect of PAcP by utilizing cDNA direct intratumoral administration in androgen-independent LNCaP xenograft tumors. METHODS: An androgen-independent LNCaP cell model (C-33 and C-81 cells) and stable subclones of PAcP cDNA-transfected C-81 cells (LNCaP-23 and LNCaP-34 cells) were used for the experiments. We examined the growth property and expression of PAcP and c-ErbB-2 of these different LNCaP cells in vitro and in vivo. We subsequently investigated the growth suppression effect of PAcP cDNA intratumoral injection in pre-established C-81 xenograft tumors, and analyzed the expression of PAcP, prostate-specific antigen (PSA), proliferating cell nuclear antigen (PCNA), and c-ErbB-2 in the tumors by immunohistochemistry and Western blotting. RESULTS: The different LNCaP cells exhibited different growth property and tumorigenicity, both in cell culture and xenograft. Biochemical characterizations revealed that the level of cellular PAcP correlated negatively with the growth property of different LNCaP cells, while the level of tyrophosphorylated c-ErbB-2 had an inverse correlation with cellular PAcP. The single intratumoral administration of the wild type PAcP cDNA showed a significant suppression effect on C-81 xenograft tumor growth, compared to vector alone-injected control (P<0.05). In the tumors injected with this PAcP cDNA, the PAcP expression was detected 1 week (wk) after injection, but was undetectable at 6 wk, which inversely correlated with the level of tyrophosphorylated c-ErbB-2 and the degree of cell proliferation indicated by PCNA staining. CONCLUSIONS: Our results clearly demonstrated that cellular PAcP has a suppression effect on the growth of androgen-independent LNCaP xenograft tumors. This effect occurs at least partly through the dephosphorylation of c-ErbB-2 by PAcP, the prostate-specific protein tyrosine phosphatase. The data indicates that human PAcP could be utilized in the corrective gene therapy for a subgroup of androgen-independent human prostate cancer cells that lack cellular PAcP expression.     

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.     

Histochemical study of R1881-binding protein, prostatic acid phosphatase, prostate-specific antigen, and r-seminoprotein in prostatic cancer

A histochemical study on R1881-binding protein, prostatic acid phosphatase (PAP), prostate-specific antigen (PA) and r-seminoprotein was conducted. These parameters and histologic grades were compared to each other and with the responsiveness to endocrine therapy. A good correlation was found between histologic grade and presence or absence of R1881-binding protein in the tissue. Presence or absence of R1881-binding protein as well as histologic grade correlated well with responsiveness to endocrine therapy. Positive staining patterns of PAP, PA, and r-seminoprotein in the tissues were similar to each other, particularly between PA and r-seminoprotein. However, no correlation was found between the histologic grade and ratios of PAP, PA or r-seminoprotein-positive cells. Nor was any correlation seen between the ratio of these marker-positive cells and responsiveness to endocrine therapy.