PSA Monitoring Research Articles

Surprising activity of nilutamide in post-castration progressive prostate cancer

4762 Background: Increasingly patients with post-castration prostate cancer seek treatment for PSA only progression. Many of these patients are elderly, have considerable co-morbidities, are concerned about a rising PSA, and seek relatively non-toxic therapies. Methods: Twelve patients with progressive post-castration prostate cancer were treated with oral nilutamide at FDA approved doses (150 mg/day). LHRH agonist maintenance therapy was continued in non-surgically castrated patients. Monthly PSA monitoring was recommended. PSA progression was defined as a 25% increase from baseline or nadir with a minimum increase of 5 ng/ml as recommended by Bubley et al (J Clin Oncol 17:3461). Results: All patients had failed either orchiectomy (n=2) or LHRH agonist therapy (n=10) and had clear evidence of a rising PSA prior to starting nilutamide. Median age was 81 (range 62–87), median PSA was 12 ng/ml (range 2.7–92.1), and radiographically positive metastatic disease was present in 33% (4/12). Antiandrogens were previously used in 50% of patients (5/12 were bicalutamide pretreated, 1/12 were pretreated with flutamide). PSA declines were noted in 9/12 patients; PSA declines of >50% were noted in 4/12 (33%) patients. Median progression free survival was 7 months (range 1–36+). One patient had CT evidence of progression without PSA progression. Progression-free survival of more than 6 months was noted in both antiandrogen (4/6) and non-antiandrogen (2/6) pretreated patients. One patient became nauseated after four doses and refused further therapy, two patients had fatigue and weight loss and stopped therapy prior to PSA progression. No other toxicities were noted except alterations in visual light-dark adaptation Conclusions: Nilutamide at FDA approved dosages can delay PSA progression in patients with prostate cancer failing to respond to primary androgen deprivation therapies. Toxicities necessitated cessation of therapy in 3/12 patients. No significant financial relationships to disclose.

Surprising activity of nilutamide in post-castration progressive prostate cancer

4762 Background: Increasingly patients with post-castration prostate cancer seek treatment for PSA only progression. Many of these patients are elderly, have considerable co-morbidities, are concerned about a rising PSA, and seek relatively non-toxic therapies. Methods: Twelve patients with progressive post-castration prostate cancer were treated with oral nilutamide at FDA approved doses (150 mg/day). LHRH agonist maintenance therapy was continued in non-surgically castrated patients. Monthly PSA monitoring was recommended. PSA progression was defined as a 25% increase from baseline or nadir with a minimum increase of 5 ng/ml as recommended by Bubley et al (J Clin Oncol 17:3461). Results: All patients had failed either orchiectomy (n=2) or LHRH agonist therapy (n=10) and had clear evidence of a rising PSA prior to starting nilutamide. Median age was 81 (range 62–87), median PSA was 12 ng/ml (range 2.7–92.1), and radiographically positive metastatic disease was present in 33% (4/12). Antiandrogens were pr...

A seven-year follow-up of men following a benign prostate biopsy.

To determine the incidence and clinical relevance of newly diagnosed cases of prostate cancer in a group of men who had an elevated PSA and benign prostate biopsy 7 years previously. Patients under the age of 80 years with an elevated PSA who had had a benign prostate biopsy in the 12 months between March 1, 1994 and February 28, 1995 were studied. One hundred and sixty four patients with a mean age of 66.8 years (range 47-79 years) were identified. The mean PSA for this group was 10.3ng/ml (range 4.1-81ng/ml). One hundred and fifty nine of the 164 (97%) hospital records were available for review and all but 21 (12.8%) of the General Practitioners were contacted. Eighteen (11%) of the original 164 patients were subsequently diagnosed with prostate cancer, 2 died from their disease. In a population where the follow-up of patients with a benign biopsy was arranged on clinical grounds alone, 11% of the study group were diagnosed with prostate cancer during a seven-year follow-up. Although some of these cancers appear to be slow growing, most of those diagnosed in the initial follow-up period were deemed to be clinically significant and a small proportion progressed rapidly to metastases. All patients who have an elevated PSA, but benign biopsy, should undergo a period of PSA monitoring until it is clear that their PSA is not rising. We propose an initial intensive monitoring period to avoid missing those with clinically aggressive disease.

Use of early PSA velocity to predict eventual abnormal PSA values in men at risk for prostate cancer.

The purpose of this study was to determine if early PSA velocity (EPSAV), drawn from PSA values within normal ranges, predicts the later occurrence of abnormally high PSA values or positive prostate biopsy early enough to be clinically beneficial. Early PSAV (ng/ml/y) calculated from two normal PSA readings was tested to predict later PSA exceeding 4 ng/ml (1551 evaluable patients) or 10 ng/ml (1905 evaluable patients) and positive prostate biopsy. The time from EPSAV to develop abnormal PSA was recorded.A post-EPSAV PSA>4 ng/ml was reached by 367 patients and >10 by 293. EPSAV was significantly different (P<0.001) between patients whose PSA did or did not reach the PSA cut-off point and also significantly predicted a positive biopsy result (P<0.001). EPSAV predicted abnormal PSA more than 1 y in advance in 68 and 52% of the PSA 4 and 10 ng/ml cut-off point groups, respectively. Early PSAV from normal PSA readings may allow early detection of men at risk for prostate cancer. This may help identify men for earlier prostate biopsy or for less frequent PSA monitoring.

PADAM from the urologic viewpoint

PADAM stands for partial androgen deficiency in the aging male, and it is currently diagnosed with a testosterone level below 3 ng/ml (300 ng/dl or 12 nmol/l), and with symptoms varying according to the individual. The symptoms are a reduction or even loss of libido, a decline in muscle mass and strength, enhancement of visceral fatty tissue-padding, dryness of the skin, apathy, tiredness and distortion of mood right up to depression, and ostalgia due to osteoporosis. Before starting any form of hormonal substitution, which is only indicated if clinical symptoms and testosterone deficiency correlate, it is absolutely essential to exclude prostate cancer by using clinical evaluation and PSA values. Close PSA monitoring is necessary during testosterone substitution. In more than 95% of all patients with erectile dysfunction, the cause is not testosterone deficiency. Even a decreased level of dehydroepiandrosterone (DHEA) in an elderly male needs no replacement. There is also no indication for estradiol therapy in men--except in the rare case of aromatase deficiency.

An ultrasensitive immunoassay for prostate-specific antigen based on conventional colorimetric detection

Objective: Development of an ultrasensitive immunoassay for serum PSA involving conventional detection probes. Design and Methods: The assay involves a polyclonal antibody immobilized in microtitration Wells and a monoclonal antibody labeled with horseradish peroxidase. In a one-step assay, the enzymatic activity of the bound detection antibody is monitored by the addition of hydrogen peroxide/tetramethylbenzidine substrate reagent followed by spectrophotometric quantification of the conversion product. Results: The assay has a lower detection limit of 0.003 μg/L, biological detection limit of 0.009 μg/L, and intra- and inter-assay CVs of 8.2% and 10.5% at PSA concentrations of 0.022 and 0.065 μg/L, respectively. The recovery of the assay averaged 104% and it demonstrated a dilution linearity down to at least 0.01 μg of PSA/L. Results of comparison data correlated well with those obtained by a well established enzyme immunoassay. The serum PSA concentrations were <0.012 μg/L in the majority of patients (53.8%) who had undergone radical prostatectomy. Conclusions: This assay is well suited for post-surgical monitoring of PSA in patients with prostate cancer.