Serum Prostate-specific Antigen Measurement Research Articles

Detection and Quantification of Protein Biomarkers from Fewer than 10 Cells

The use of antibody microarrays continues to grow rapidly due to the recent advances in proteomics and automation and the opportunity this combination creates for high throughput multiplexed analysis of protein biomarkers. However, a primary limitation of this technology is the lack of PCR-like amplification methods for proteins. Therefore, to realize the full potential of array-based protein biomarker screening it is necessary to construct assays that can detect and quantify protein biomarkers with very high sensitivity, in the femtomolar range, and from limited sample quantities. We describe here the construction of ultramicroarrays, combining the advantages of microarraying including multiplexing capabilities, higher throughput, and cost savings with the ability to screen very small sample volumes. Antibody ultramicroarrays for the detection of interleukin-6 and prostate-specific antigen (PSA), a widely used biomarker for prostate cancer screening, were constructed. These ultramicroarrays were found to have a high specificity and sensitivity with detection levels using purified proteins in the attomole range. Using these ultramicroarrays, we were able to detect PSA secreted from 100 LNCaP cells in 3 h and from just four LNCaP cells in 24 h. Cellular PSA could also be detected from the lysate of an average of just six cells. This strategy should enable proteomic analysis of materials that are available in very limited quantities such as those collected by laser capture microdissection, neonatal biopsy microspecimens, and forensic samples.

Imaging androgen receptor function during flutamide treatment in the LAPC9 xenograft model

The current understanding of the response of androgen receptor to pharmacologic inhibitors in prostate cancer is derived primarily from serum prostate-specific antigen (PSA) levels. In this study, we test whether a novel androgen receptor-specific molecular imaging system is able to detect the action of the antiandrogen flutamide on androgen receptor function in xenograft models of prostate cancer. Adenoviruses bearing an optical imaging cassette containing an androgen receptor-responsive two-step transcriptional amplification system were injected into androgen-dependent and hormone-refractory tumors of animals undergoing systemic time-controlled release of the antiandrogen flutamide. Imaging of tumors with a cooled charge-coupled device camera revealed that the response of AdTSTA to flutamide is more sensitive and robust than serum PSA measurements. Flutamide inhibits the androgen signaling pathway in androgen-dependent but not refractory tumors. Analysis of androgen receptor and RNA polymerase II binding to the endogenous PSA gene by chromatin immunoprecipitation revealed that flutamide treatment and androgen withdrawal have different molecular mechanisms. The application of imaging technology to study animal models of cancer provides mechanistic insight into antiandrogen targeting of androgen receptor during disease progression.

Phase II study of oral capecitabine in patients with hormone-refractory prostate cancer

Currently available treatment for hormone refractory prostate cancer is limited in efficacy and associated with significant toxicity. This phase II study was performed to assess the efficacy of the oral fluoropyrimidine capecitabine in advanced prostate cancer. Patients who had a rising prostate-specific antigen (PSA) despite androgen withdrawal, but who remained free from cancer-related symptoms. In total, 14 patients received oral capecitabine 1250 mg/m2 twice daily for two weeks of a three-week cycle. Tumour response was assessed using serum PSA measurement at 3-weekly intervals and, where present, imaging of soft tissue metastases. One of 14 patients experienced a partial response as assessed by both PSA and imaging of liver metastases. In seven other patients (50%), treatment decreased the rate of PSA rise. The duration of PSA stabilisation was generally short, but in 5/14 patients (36%) was sustained beyond 18 weeks, and in one patient to 24 weeks. Toxicity was significant but manageable, the most common adverse events being nausea, mucositis and hand-foot syndrome, each occurring in 50% of patients. Other common side effects were diarrhoea and lymphopenia. All toxicities were grade 1 or 2, except for grade 3 hand-foot syndrome occurring in one patient, and no dose reduction was required because of toxicity. Capecitabine has limited activity as a single agent in prostate cancer, but appears to modulate tumour biology. Considering the added convenience of oral administration, these results support further evaluation of combinations containing capecitabine in hormone-refractory prostate cancer.

Neoadjuvant Docetaxel before Radical Prostatectomy in Patients with High-Risk Localized Prostate Cancer

To determine the clinical, pathologic, and molecular effects of neoadjuvant docetaxel chemotherapy in high-risk localized prostate cancer. Patients with biopsy Gleason scores of 8 to 10, serum prostate-specific antigen levels >20 ng/mL, and/or clinical stage T3 disease received weekly docetaxel (36 mg/m2) for 6 months, followed by radical prostatectomy, and were monitored with weekly visits, serum prostate-specific antigen measurements, and endorectal magnetic resonance imaging (MRI). Frozen tumor specimens were collected for microarray analysis. The 19 patients enrolled received 82% of the planned chemotherapy. Toxicity was mild to moderate; fatigue and taste disturbance were common. Prostate-specific antigen declines of >50% were seen in 11 of 19 patients (58%; 95% confidence interval, 33-80%) and endorectal MRI showed maximum tumor volume reduction of at least 25% in 13 of 19 patients (68%; 95% confidence interval, 47-85%) and at least 50% in 4 patients (21%; 95% confidence interval, 6-46%). Sixteen patients completed chemotherapy and had radical prostatectomy; none achieved pathologic complete response. Microarray analysis identified coordinate up-regulation of genes involved in androgen metabolism associated with docetaxel therapy. Specifically, RNA expression for genes that decrease cellular levels of bioactive androgens was coordinately increased in response to chemotherapy. Neoadjuvant docetaxel administered for 6 months before radical prostatectomy is feasible, well tolerated, and often results in prostate-specific antigen declines of >50% and decreased tumor volume on endorectal MRI. No pathologic complete responses were observed. Altered androgen metabolism may partially account for the noted declines in prostate-specific antigen and be a mechanism for chemotherapy resistance.

Is serum prostate-specific antigen level affected by fasting and nonfasting?

Objectives To determine whether the level of serum prostate-specific antigen (PSA) varies with fasting and nonfasting. Methods The study involved 80 male patients with normal digital rectal examination who were hospitalized for benign urologic problems. The patients with active urinary tract infection, urologic cancer, urethral catheterization, diabetes mellitus, or acute or chronic renal failure and those who had undergone urologic manipulations within the past 45 days were excluded from the study. All the patients were asked to fast between 12:00 am and 8:00 am. The next morning, 10-mL venous blood samples were obtained at 8:00 am. Then each patient was provided with breakfast, which was followed by additional serial venous serum sampling during the first and second hour. The patients ate lunch at 12:00 pm. The final venous serum sampling was conducted at 2:00 pm. The serum PSA levels were determined for all the serum samples. Results The mean patient age was 62.42 ± 8.75 years (range 46 to 82). The mean serum total PSA value at fasting and the first, second, and sixth hour was 2.78 ± 2.19, 2.7 ± 2.0, 2.7 ± 2.1, and 2.78 ± 2.10 ng/mL, respectively. In the comparisons of the fasting values and first, second, and sixth hour values and the values at each hour with those at the other hours, no significant differences were observed ( P >0.05). Conclusions According to our results, blood samples can be obtained for serum PSA measurement at any time of the day, regardless of whether the patient has fasted or not.

Population Standards of Prostate Specific Antigen Values in Men over 40: Community Based Study in Turkey

To determine the prostate specific antigen (PSA) population standards of a cluster of Turkish men with no clinical evidence of prostate cancer. We evaluated PSA values of the men who were living in a well-defined, rural district of Western Anatolia. Two hundred fifty-seven men agreed to participate in this population-based study. They underwent clinical examination, transrectal ultrasonography and serum PSA measurement. The association between serum PSA and age, prostate volume and age, PSA and prostate volume, and PSA density (PSAD) and age were assessed. Distributions of serum PSA levels, prostate volumes (PV), and PSAD values as a function of age were generated. The upper limit of normal PSA concentration were 4.51 ng/ml for men aged 40-49 years, 4.36 ng/ml for 50-59 years, 6.17 ng/ml for 60-69 years, and 10.18 ng/ml for over 70 years. The upper limit of normal (95th percentile) for the serum PSA concentration increased with age. Across the entire age range, no correlation was found between the serum PSA concentrations and age while significant correlation was found between serum PSA concentration and prostate volume. In this present study, the PSA values in different age intervals showed higher than those observed in previous studies. The PSA values are mainly affected by prostate volume rather than age.

Second-line chemotherapy with docetaxel for prostate-specific antigen (PSA) relapse in men with hormone-refractory prostate cancer (HRPC) previously treated with docetaxel-based chemotherapy

4682 Background: Docetaxel-based chemotherapy has demonstrated a significant survival benefit in men with HRPC. However, about 80% of patients demonstrate PSA relapse within 12 months and median time to progression is approximately 6 months after an initial response to docetaxel. Thus, we evaluated repeat treatment with low-dose docetaxel for men with HRPC and PSA progression. The primary endpoint was PSA response (PSA decrease ≥50%). Methods: Twenty-five consecutive patients with PSA progression after docetaxel-based chemotherapy were enrolled. PSA progression was defined as a continuous increase in PSA measured at 3 consecutive points 2 weeks apart and a PSA level ≥2x nadir after the first 12-week cycle or the previous chemotherapy cycle. PSA doubling time was ≤6 months in all patients. Docetaxel 35 mg/m2 was given on Days 2, 9, and 16 of a 4-week cycle x 3 cycles. Treatment was stopped in patients with stable disease or a PSA response (≥50% decrease in PSA from baseline, confirmed after 4 weeks). Patients were monitored with serial PSA measurements at 4-week intervals and the same 12-week sequence was restarted in patients with PSA progression. Patients who progressed during therapy were withdrawn and received palliative care. Results: Median baseline PSA level was 34.3 (range: 15–189) ng/mL. A PSA response was achieved by 18/25 (72%) patients; mean duration of response was 5.8 (range: 3–10) months. To date, 5 patients have undergone a second 12-week sequence of docetaxel owing to PSA progression; 3/5 (60%) subsequently achieved a PSA response (median follow-up: 8.5 (range: 3–15) months. Hematologic toxicity was acceptable: 5 patients (20%) and 3 patients (12%) had NCI-CTC grade 3–4 anemia and leukopenia, respectively. Grade 3–4 nonhematologic toxicities were nail changes (5 patients; 20%), diarrhea (3 patients; 12%), and fluid retention (3 patients; 12%). Conclusions: These results suggest that rechallenge with low-dose intermittent docetaxel may be an effective and well-tolerated treatment option in men with HRPC and PSA progression following an intial response to docetaxel-based chemotherapy. No significant financial relationships to disclose.

Prognostic and predictive factors in prostate cancer: Historical perspectives and recent international consensus initiatives

An understanding of prognosis in cancer medicine is important for patient care, research and cancer control programs. In prostate cancer, prognostic (predictive) factors are particularly important given the marked heterogeneity of this disease at clinical, morphologic and biomolecular levels. Clinical stage and histologic grade have historically played major roles in defining heterogeneity in prostate cancer. More recently, serum prostate-specific antigen measurement has assumed a significant prognostic role. Over the last two decades there has been an explosion of research into biomarkers, many of which have been purported to have prognostic significance. In this paper we present an overview of the various consensus initiatives that have transpired over the last dozen years. Criteria for evaluating prognostic factors and classifications of predictive factors have emerged that have proven useful and advanced our understanding of the biology of prostate cancer. The results of these consensus initiatives form a foundation on which the current international consultation on prognosis (prediction) in prostate cancer is built. Advances in our understanding of the new and promising prognostic factors will require a more rigorous evidence-based approach to the analysis of published studies. Furthermore, appropriate mathematical models for the analysis of the multiple factors that influence a prognostic system will have to be employed.

Prostate-specific antigen velocity accurately predicts response to salvage radiotherapy in men with biochemical relapse after radical prostatectomy

Objectives To determine whether prostate-specific antigen (PSA) velocity (PSAV), used as a selection criterion for salvage radiotherapy (RT) after radical prostatectomy (RP), predicts the likelihood of response to RT in men with biochemical relapse. Methods We retrospectively reviewed the records of 48 patients who had undergone salvage RT for biochemical relapse after RP. All men were followed up with serial PSA measurements for a minimum of 6 months from their initial PSA recurrence, and RT was only offered to those patients with a serum PSA level remaining at less than 1.0 ng/mL. The response to RT was defined as maintenance of a PSA level of less than 0.1 ng/mL. The pathologic and clinical parameters, including PSAV, were examined to determine their individual ability to predict the response to RT. Results Of the 48 patients, 30 had maintained a PSA level of less than 0.1 ng/mL at a median follow-up of 16 months. The PSAV was strongly predictive of the likelihood of a response to salvage RT. The median relapse-free survival time for patients with a PSAV of less than 0.035 ng/mL/mo was 28 months compared with 16 months for patients with a PSAV greater than 0.035 ng/mL/mo. All other parameters tested, including Gleason score, seminal vesicle invasion, extracapsular extension, and margin status, were not predictive of the likelihood of a response to RT. Conclusions In the present study, PSAV accurately predicted the likelihood of response to salvage RT in men with biochemical relapse after RP. No other pathologic parameters predicted the likelihood of response to RT. Using PSAV as a sole selection criterion for salvage RT after RP may allow improvement in the historically low rates of durable response.

Prostate specific antigen as a clinical biomarker for prostate cancer: What’s the take home message?

Prostate specific antigen (PSA) continues to be challenged as a legitimate clinical biomarker in early detection of prostate cancer due to lack of specificity for malignant transformation. Skepticism surrounding the utility of serum PSA as a clinical marker is not new and many questioned its initial use in widespread prostate cancer screening due to non-specific expression and low predictive value for cancer detection. Despite these initial concerns, serum PSA measurement along with digital rectal examination (DRE) is currently the accepted practice for prostate cancer screening in the United States with hundreds of thousands of men undergoing serum PSA measurement annually. In contrast to its role for early detection, serum PSA measurement as a surrogate for prostate cancer recurrence (biochemical failure) following curative intent therapy has consummate clinical utility in post-treatment surveillance. As thousands of men each year are aggressively treated for potentially curable prostate cancer, development of simple and effective diagnostic tools for detecting treatment failures should be an important area of biomedical and clinical investigation. We have constructed and tested a home-based prostate cancer surveillance device for use by patients to detect PSA from blood obtained by finger stick. Our initial results suggest that home based PSA testing is feasible and may have clinical utility in management of men treated for prostate cancer.

BRACHYTHERAPY OF PROSTATE CANCER AFTER COLECTOMY FOR COLORECTAL CANCER: PILOT EXPERIENCE

We present a method of brachytherapy for prostate cancer using a 3-dimensional stereotactic system and computerized tomography guidance in patients without a rectum due to previous treatment for colorectal cancer. From June 1994 to November 2003 a cohort of 800 patients were treated with brachytherapy for prostate cancer. Four patients had previously been treated for colorectal cancer with 4,500 cGy external beam radiation therapy, abdominoperineal resection and chemotherapy, while 1 underwent abdominoperineal resection alone for ulcerative colitis. Because of previous radiation therapy, these patients were not candidates for salvage external beam radiation therapy or radical prostatectomy and they had no rectum for transrectal ultrasound guided transperineal brachytherapy or cryotherapy. A previously described, 3-dimensional stereotactic system was used for brachytherapy in these patients. The prescribed radiation dose was 120 to 144 Gy with iodine seeds in rapid strand format. Patient followup included clinical examination and serum prostate specific antigen measurement. Average followup was 18.6 months. Four patients had excellent biochemical control, while 1 had biochemical failure. Patients did not experience any gastrointestinal morbidity. One patient had a stricture of the distal ureter, requiring a stent. Three-dimensional computerized tomography guided brachytherapy for prostate cancer in patients with a history of colorectal cancer who have no rectum is a feasible method of treatment.

The effect of acute urinary retention on serum prostate-specific antigen level.

Our aim was to evaluate the effect of acute urinary retention on serum prostate-specific antigen (PSA) level. Men aged 50 years and older who presented with acute urinary retention were studied. Patients with urethral stricture, neurogenic bladder, prostate cancer, and those with a history of recent instrumentation or prostate biopsy were excluded. Blood samples for serum PSA measurement were obtained (PSA1), and an indwelling urethral catheter was inserted for 2 weeks. Before catheter removal, a second blood sample for measurement of serum PSA level (PSA2) was obtained. In patients who were able to void, a third sample was obtained 3 weeks later (PSA3). In the first and second visits, digital rectal examinations (DRE1, DRE2) were performed to assess prostate volume. Mean PSA levels (PSA1, PSA2, and PSA3) and prostate volumes (DRE1, DRE2) were compared. Forty-five patients with a mean age of 70.18 years (range 56 to 85 years) participated in this study. Mean PSA1 and PSA2 levels were 9.8 ng/mL and 5.05 ng/mL, respectively (P < 0.001; medians, 6.2 and 4.2 ng/mL). Mean prostate volumes at the time of retention and 2 weeks later were 43.4 mL and 37.8 mL, respectively (P < 0.001; medians, 45 and 40 mL). PSA3 was measured in 31 patients 2 weeks after catheter removal. In this group of patients, mean PSA2 and PSA3 levels were 5.03 ng/mL and 4.97 ng/mL, respectively (P = 0.49; medians, 4.3 and 4.1 ng/mL). Acute urinary retention can increase serum PSA levels by approximately 2 fold. In this series, we found that this effect may continue up to 2 weeks.

FERROMAGNETIC THERMAL ABLATION OF LOCALLY RECURRENT PROSTATE CANCER: PROSTATE SPECIFIC ANTIGEN RESULTS AND IMMEDIATE/INTERMEDIATE MORBIDITIES

Curative options for locally recurrent prostate cancer following external beam radiotherapy are limited due to the significant morbidity associated with surgical therapy. ThermoRods (Ablation Technologies, San Diego, California) are permanently implantable, 14 mm cobalt-palladium alloy rods that produce heat through oscillation of a magnetic field. The rod is designed to self-regulate the temperature to 70C by a temperature dependent magnetic transition (Curie effect). We determined whether patients with prostate cancer and local failure could be treated with thermal ablation of the prostate using this novel technology. A total of 14 men with an average age of 72 years (range 62 to 81) were enrolled in the study. All had biopsy proven prostate cancer with increasing prostate specific antigen (PSA) (1.0 to 10.3 ng/ml). The seminal vesicles were not routinely biopsied. Metastatic disease was assayed in all men with bone scan and in later patients with abdominopelvic computerized tomography. Patients had ThermoRods placed under transrectal ultrasound guidance, similar to brachytherapy. The pre-plan was rigorously followed to produce a 3-dimensional array with rods separated by 1 cm across the short axis. Patients were treated in a magnetic field for 1 hour. Urethral and rectal temperatures were also monitored and cooled appropriately. Serial PSA measurements and 6 month posttreatment biopsies were obtained after the procedure. Average time since radiation was 4.5 years. PSA nadir values after radiation were between 0.3 and 2.2 ng/ml. Prostatic temperatures were homogeneously increased greater than 50C, while rectal and urethral temperatures did not exceed 44C at any point. The urethral catheter was removed 2 weeks postoperatively in all cases. Six months after the procedure 8 of the 14 men (57%) had a PSA decrease to less than 0.1 ng/ml. Complications included urinary retention as well as incontinence. Incontinence was generally temporary and only 1 patient (7%) had long-term incontinence. Most patients were impotent after treatment. Of the patients 21% experienced urinary retention. Five patients (36%) needed to undergo secondary procedures after therapy, including transurethral prostate resection in 2, balloon dilation in 1, cystoscopic removal of necrotic tissue in 1 and bladder irrigation in 1. This novel means of thermal ablation produces significant PSA decreases in patients. Morbidity is predominantly in the form of incontinence and impotence. Incontinence is generally temporary. The use of ferromagnetic rods enables the precise control of tissue destruction with the sparing of immediately adjacent structures. The technology uses skills familiar to the urologist and avoids radiation. The durability of the PSA response and incidence of late morbidity remain to be defined.

Proteomic analysis of voided urine after prostatic massage from patients with prostate cancer: A pilot study

Objectives Serum prostate-specific antigen measurements are widely used for the early detection of prostate cancer but lack specificity, thus warranting the search for additional biomarkers. Methods Two-dimensional gel electrophoresis followed by matrix-assisted laser desorption ionization–time of flight–mass spectroscopy (MALDI-TOF-MS) analysis was used to investigate the protein profiles of voided urine after prostatic massage from 6 patients with histologically confirmed prostate cancer and 6 age-matched patients with benign prostatic hyperplasia. Results The median number of protein spots per gel was lower in the urine from the patients with cancer (median 143 spots, range 118 to 163) than in the urine from those with benign prostatic hyperplasia (median 154 spots, range 142 to 209), although the difference was not statistically significant. MALDI-TOF-MS analysis identified six commonly expressed proteins: alpha-enolase, isocitrate dehydrogenase, beta-2-microglobulin, alpha-1-microglobulin, complex-forming glycoprotein HC, and PRO2044. Of the five protein spots seen in a subset of patients with cancer, one was identified as calgranulin B/MRP-14. Immunohistochemical staining of prostatic tissue showed greater expression of calgranulin B/MRP-14 in 2 of 7 well-differentiated, 1 of 12 moderately differentiated, and 0 of 8 poorly differentiated tumors relative to adjacent benign tissue; expression of calgranulin A/MRP-8, a heterodermic binding partner of calgranulin B/MRP-14, was absent. Conclusions The role of urinary calgranulin B/MRP-14 as a potential novel marker for prostate cancer needs additional investigation.

Results of a Randomized, Population-Based Study of Biennial Screening Using Serum Prostate-Specific Antigen Measurement to Detect Prostate Carcinoma

BACKGROUND. The purpose of the current study was to evaluate the effectiveness of a prostate carcinoma screening program in which serum prostate-specific antigen (PSA) levels were measured. METHODS. From a group of 20,000 men born between January 1, 1930, and December 31, 1944, 10,000 men were randomized into a screening group and 10,000 were randomized into a control group. Patients in the screening group were invited to undergo initial PSA testing between 1995 and 1996 and then were invited to receive testing every second year thereafter for 8 years (for a total of 4 PSA tests). Men with PSA levels 3 ng/mL (or 2.54 ng/mL, in the third and fourth screening rounds) were invited to undergo clinical investigation, which included sextant biopsy of the prostate. By linking to the regional cancer registry, the authors were able to obtain the true and expected incidence rates for the screening and control groups. RESULTS. The screening participation rate was high (73%). A total of 884 malignancies have been detected to date, with 640 having been detected in the screening group. There was an early and marked shift toward more favorable disease stage and grade for malignancies detected on repeat screening. In the fourth screening round, only 2 of 82 detected malignancies were classified as advanced disease. Of the 227 screen-detected tumors on which surgery was performed, only 20 (8.8%) had small volume ( 0.2 cm). Forty-three interval malignancies were detected, but only five were accompanied by symptoms. At 8 years, the cumulative disease incidence rate among screening participants was 7.3%, compared with 2.4% in the control arm. The incidence rate observed in the screening population corresponds to the cumulative incidence rate observed in the Swedish male population at age 72 years. CONCLUSIONS. Biennial PSA screening was very successful in diagnosing prostate carcinoma at an early stage, when curative treatment typically is effective. In addition, the results regarding interval malignancies were favorable. Thus, decreased mortality should be observed on long-term follow-up. The lead time associated with screening appears to fall within the range described in earlier studies involving frozen sera (i.e., 5–9 years).

Molecular diagnosis of prostate cancer.

The diagnosis, staging, and management of prostate cancer as we know it today is greatly dependent on our ability to measure serum prostate-specific antigen (PSA) concentration. Nevertheless, because serum PSA concentration, particularly when less than 10 ng/mL, reflects the presence of benign prostatic hyperplasia more often than cancer, there is a clear need for more specific prostate cancer markers. The most promising new markers for prostate cancer are the various molecular forms of free PSA. Mass spectrometry also is emerging as a potential tool in prostate cancer screening. Because it is unlikely that any one marker will have 100% sensitivity and specificity, as new serum markers are tested, nomograms that incorporate multiple independently predictive parameters for the detection of prostate cancer will become indispensable in our efforts to improve prostate cancer screening.

Serum prostate specific antigen levels in women with polycystic ovary syndrome and the effect of flutamide+desogestrel/ethinyl estradiol combination.

Prostate-specific antigen (PSA) is expressed in many female tissues and its concentrations were higher in hirsute subjects. We aimed to determine serum PSA level in hirsute women and evaluate the effect of flutamide+desogestrel/ethynil estradiol combination. Thirty patients with polycystic ovary syndrome (PCOS) and 30 healthy controls were studied. Hirsutism was defined by modified Ferriman-Gallwey score (FGS). Free androgen index (FAI) was used for hyperandrogenism. Patients received flutamide (500 mg/d) and oral contraceptive (desogestrel+ethinyl estradiol) for 9 months. Mean FGS (p<0.0001), insulin (p<0.01), FAI (0.0001), androstenedione (p<0.0001), LH (p<0.05), and free testosterone (p<0.003) levels of patients with PCOS were higher than the control group. Mean serum total and free PSA level of PCOS patients were higher than the control group (p<0.0001 and p<0.0001). We found a positive correlation between total PSA levels and FGS (r=0.568, p<0.001), FAI and FGS (r=0.456 and p<0.01). There was also a positive correlation between FAI and total PSA (r=0.503 and p<0.005). At the end of treatment, FGS, androstenedione, free and total testosterone, FAI, serum PSA and LH levels decreased significantly [serum total PSA was 0.0208 +/- 0.0178 ng/ml at baseline and 0.0061 +/- 0.0044 ng/ml after treatment (p<0.0001)]. 1. Serum prostate specific antigen level is higher in patients with PCOS; 2. There is a positive correlation among FGS, FAI and PSA levels; 3. Serum PSA levels decrease with antiandrogen treatment; 4. Serum PSA measurement might be a marker for hirsutism.

Serum Total Prostate-Specific Antigen Assay in Women with Cushing’s Disease or Alcohol-Dependent Pseudo-Cushing’s State

Background: The distinction between Cushing’s disease (Cushing’s syndrome dependent on adrenocorticotropic hormone (ACTH)-secreting tumors of pituitary origin) and pseudo-Cushing’s states (Cushingoid features and hypercortisolism sometimes present in alcoholic, depressed or obese subjects) can present a diagnostic challenge in clinical endocrinology. Recently, the availability of a highly sensitive immunofluorometric assay for the measurement of total prostate-specific antigen (PSA) provided the possibility to measure serum PSA levels in women. Interestingly, PSA gene expression and protein production has been found to be upregulated by steroid hormones, such as androgens, glucocorticoids, mineral corticoids and progestins. In fact, serum total PSA concentrations appear to be higher in female patients with Cushing’s disease than in normal women. We wondered whether a similar phenomenon also occurs in pseudo-Cushing’s state. Methods: In order to answer this question, we compared the serum total PSA levels measured in 10 female subjects with alcohol-dependent pseudo-Cushing’s state with those observed in 8 female patients with Cushing’s disease and in 15 age-matched healthy women. Serum testosterone, ACTH and cortisol, and 24-hour urinary cortisol levels were measured; cortisol suppression after dexamethasone was also tested in all subjects. Results: The basal serum levels of ACTH and cortisol were significantly lower in normal subjects than in patients with Cushing’s disease or pseudo-Cushing’s state; these latter groups showed similar basal hormonal values. Dexamethasone administration was unable to suppress serum cortisol levels in 5 subjects with Cushing’s disease and 6 subjects with pseudo-Cushing’s state. Serum testosterone values in the group with Cushing’s disease were higher than in the other groups. No differences were observed between pseudo-Cushing’s and normal subjects. Serum total PSA levels were significantly higher in women with Cushing’s disease than in subjects with pseudo-Cushing’s state and normal controls; these latter groups showed similar PSA values. When serum total PSA and testosterone levels were considered together, a significant positive correlation was observed in the group with Cushing’s disease, but not in the other groups. Conclusions: These data indicate that the steroid milieu responsible for the elevation in serum PSA in women with Cushing’s disease is not present in subjects with alcohol-dependent pseudo-Cushing’s state, suggesting the possible use of PSA as a marker of differentiation between these pathological conditions in women.

Individualized Predictions of Disease Progression Following Radiation Therapy for Prostate Cancer

Following treatment for localized prostate cancer, men are monitored with serial prostate-specific antigen (PSA) measurements. Refining the predictive value of post-treatment PSA determinations may add to clinical management, and we have developed a model that predicts future PSA values and the time to future clinical recurrence for individual patients. Data from 934 patients treated between 1987 and 2000 were used to develop a comprehensive statistical model to fit the clinical recurrence events and patterns of PSA data. A logistic model was used for the probability of cure, mixed models were used for serial PSA measurements, and a proportional hazards model was used for recurrences. Data available through February 2001 were fit to the model, and data collected between February 2001 and September 2003 were used for validation. T-stage, baseline PSA, and radiotherapy dosage are all associated with probability of cure. The risk of clinical recurrence in those not cured is strongly affected by the slope of PSA values. We show how the model can be used for individual monitoring of disease progression. For each patient the model predicts, based on baseline characteristics and all post-treatment PSA values, the probability of future clinical recurrences and future PSA values. The model accurately predicts risk of recurrence and future PSA values in the validation data set. This predictive information on future PSA values and the risk of clinical relapse for each individual patient, which can be updated with each additional PSA value, may prove useful to patients and physicians in determining post-treatment salvage strategies.

徳島市前立腺がん検診について

Screening with prostate specific antigen (PSA) only to detect prostate cancer was started in Tokushima City from 2001 as one of health check lists. We evaluated the first year result. Fifty-five years old or elder men living in Tokushima City who wants to measure serum PSA level to screen for prostate cancer were entered to screening program. The men whose PSA levels detected as over normal; range were recommended to visit to urologists for further examination to detect prostate cancer include prostate biopsy. The results of further examination were reported to Tokushima City and evaluated. The population of fifty-five or elder men in Tokushima City was 25,416 and 9,019 (35.5%) men were measured serum PSA levels. In 801 (8.9%) men, PSA levels were over normal range, and recommended further examination to detect prostate cancer. 451 (56.3%) men visited to urologists for further examination, and prostate biopsy was performed in 231 (51.2%) men. Finally, 121 men were diagnosed as prostate cancer, 52.1% of 231 men performed prostate biopsy, 26.7% of 451 men visited to urologist for further examination, 1.34% of 9,019 men measured serum PSA levels. Patient number for each clinical stages were 49 in B0, 16 in B1, 16 in B2, 29 in C, one in D1, and 10 in D2. Patients number in each age range were 3 in 55-59, 11 in 60-64, 22 in 65-69, 37 in 70-74, 33 in 75-79, 15 in 80 or elder. Patient number of Stage B and 74 years old or younger was 48 (39.7%). Prostate cancer was detected in 1.34% of 9,019 men who measured serum PSA levels, and early stage B was two thirds. PSA screening to detect prostate cancer as one of health check-lists in Tokushima City was useful to detect early prostate cancer.