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Clinical utility of percent-positive prostate biopsies in predicting biochemical outcome after radical prostatectomy or external-beam radiation therapy for patients with clinically localized prostate cancer.

BACKGROUND AND PURPOSE: The clinical utility of the percentage of positive prostate biopsies in predicting prostate specific antigen (PSA) outcome after radical prostatectomy (RP) or external-beam radiation therapy (EBRT) for men with PSA-detected or palpable prostate cancer is not established. METHODS: A Cox regression multivariable analysis was used to determine whether percent-positive prostate biopsies provided clinically relevant information about PSA outcome after RP in 960 men, while accounting for the previously established risk groups based on the pretreatment PSA concentration biopsy Gleason score, and the 1992 American Joint Commission on Cancer clinical T stage. RESULTS: In the intermediate-risk group, 80% of the patients (stage T(2b) or biopsy Gleason 7 or PSA 10-20 ng/mL) could be classified into either an 11% or an 86% 4-year PSA control cohort using the preoperative prostate biopsy data. These findings were validated using an independent surgical (N = 823) and radiation (N = 473) data set. Percent-positive prostate biopsies added clinically significant information regarding time to PSA failure after RP. CONCLUSIONS: The percentage of positive prostate biopsies should be considered in conjunction with the PSA level, biopsy Gleason score, and clinical T stage when counseling patients with newly diagnosed and clinically localized prostate cancer about PSA outcome after RP or EBRT.

Biopsy↗

Tumor-associated forms of prostate specific antigen improve the discrimination of prostate cancer from benign disease.

Prostate-specific antigen (PSA) is a widely used serum marker for prostate cancer, but has limited specificity for distinguishing early prostate cancer(PCa) from benign disease since serum PSA can leak from both tumor and prostate tissues with benign disease. Molecular forms of free PSA have been identified that are associated with either benign or malignant prostate tissues. BPSA is a form of free PSA that is associated with benign prostatic hyperplasia(BPH), the predominant benign disease in men. The inactive precursor of PSA, proPSA, is associated with prostate tumors. We have developed research immunoassays with high sensitivity and specificity for BPSA and proPSA. Each of these PSA forms can range from 0-50% of the free PSA in individual serum samples in the total PSA range of 2-10 ng/ml. Typically, BPSA represents from 20-30% of the free PSA in serum, while proPSA ranges from 30-40% of the free PSA. ProPSA greatly improves the early detection of cancer in men with less than 4 ng/ml total PSA. More importantly, proPSA is more highly associated with aggressive cancers than other PSA forms such as PSA-ACT and free PSA. The BPH-associated BPSA and cancer-associated proPSA forms are complementary and provide improved detection of prostate cancer from benign disease.

Biomarkers, Tumor↗

[Local prostatic hyperthermia in the therapy of urinary obstruction caused by prostatic adenoma. Experimental, clinico histologic and structural findings].

A specifically designed system of selective prostate heating was used to treat 197 patients with prostatic diseases: 164 benign prostatic hypertrophy cases, 14 prostatic adenocarcinoma cases, 19 chronic abacterial prostatitis cases. Ninety-one benign prostatic hypertrophy patients could be evaluated at the three month follow-up date. Sixty-eight patients complained of severe obstructive symptoms and 23 had an indwelling catheter. Prostates were heated up to 42 +/- 0.5 degrees C during 60 minute long sessions, once or twice a week for five weeks. Local prostatic hyperthermia determined a marked amelioration of the clinical picture in 67% of patients who presented without an indwelling catheter. Sixteen patients (70%) were weaned off the catheter. Major complications were not encountered.

Aged↗

Monitoring of prostate-specific antigen during external beam radiotherapy for carcinoma of the prostate.

In 35 patients with histologically confirmed carcinoma of the prostate confined to the pelvis, the value of prostate-specific antigen (PSA) was evaluated during external beam radiotherapy to the prostate and draining pelvic lymph nodes. In eleven patients initial prostate-specific antigen levels were more than 10 ng/ml and in twelve patients between 4 and 10 ng/ml. In the remaining twelve, initial prostate-specific antigen levels were less than 4 ng/ml. In the course of radiotherapy we could see a significant decrease of the prostate-specific antigen, even in those with levels between 4 and 10 ng/ml. This decrease seems to follow a logarithmic course but, because only three measurements during radiotherapy were made, this needs further study. With higher levels (more than 20 ng/ml), we rarely saw a value of less than 10 ng/ml at the end of radiotherapy but had to wait for several months for lower values to be reached. In several cases prostate-specific antigen decrease took up to three months after the end of the radiation course. Our results indicate that prostate-specific antigen values actually start decreasing during the radiation course itself and may, therefore, be useful for monitoring response to radiotherapy.

Acid Phosphatase↗

Prostate-specific antigen in prostate cancer.

Prostate-specific antigen (PA) has been evaluated clinically as a tumor marker of prostate cancer with the use of enzyme immunoassay (EIA). For serodetection of prostate cancer, PA was assayed in a total of 1,109 sera. From mean +/- 3 S.D. of normal controls, upper cut-off values in males were decided as 2.5 and 1.2 ng/ml in Americans and Japanese, respectively. Serum PA values in prostate cancer patients were positive in 78% of Americans and 62% of Japanese. However, in benign prostatic hypertrophy (BPH) cases, a high false positive rate of 41% was observed in Americans. Simultaneous assays of serum PA and PAP showed high sensitivity and specificity in the detection of prostate cancer. This antigen could be used, as well as PAP, for monitoring prostate cancer patients. Furthermore, serum PA levels prior to treatment may express to some degree the malignant potential of the cancer. These results suggest that PA may be useful as a tumor marker of prostate cancer.

Acid Phosphatase↗

[Value of determining prostate-specific antigen for early detection or prostatic carcinoma].

The use of prostate-specific-antigen in the early detection of prostatic carcinoma combined with digital-rectal examination results in a 2-3 times increase in prostatic carcinoma detection rate. 2/3 of PSA detected prostatic carcinoma are organ confined vs 40% of those which are detected by digital-rectal examination. 15-35% of all operated localized prostatic carcinoma have a normal PSA. A biopsy is indicated in men with a life expectancy of more than 10 years when the PSA value is above 10 ng/ml and/or digital-rectal examination is suspicious. This concerns only 2% of all men at the age older than 50 years. In 90% of all men older than 50 years the PSA is normal as well as the digital-rectal examination. In 4% of these the result of PSA and digital-rectal examination is false negative that means 4% have prostatic carcinoma. However, repeated digital-rectal examination and PSA determination on a yearly basis detects most of these overlooked prostatic carcinoma which still are organ confined in about 90% of the cases. In men with a minimal elevated PSA-value of 4-10 ng/ml, 25% will have a prostatic carcinoma regardless of the finding on digital-rectal examination. The indication to do a biopsy can be specified by the use of age specific PSA cut-off-levels and most likely in future by determining the free PSA vs the complex-bound PSA. Controversy exists about the usefulness of PSA-density and PSA-velocity.

Aged↗

Nuclear matrix protein patterns in human benign prostatic hyperplasia and prostate cancer.

The nuclear matrix represents the structural component of the nucleus that determines nuclear shape and higher order DNA organization. We have previously shown tissue specificity in nuclear matrix proteins (NMP), in rat sex accessory tissues, and in a rat model of prostate cancer. This study compares NMP patterns for fresh human normal prostate, benign prostatic hyperplasia (BPH), and prostate cancer for 21 men undergoing surgery for clinically localized prostate cancer or BPH. NMP patterns were compared using high resolution two-dimensional polyacrylamide gel electrophoresis. We identified by molecular weight and isoelectric point 14 different proteins that were consistently present or absent among the various tissues. One protein (PC-1), a M(r) 56,000 protein with an isoelectric point of 6.58, appeared in 14 of 14 different nuclear matrix preparations from prostate cancer and was not detected in normal prostate (0 of 13) or BPH (0 of 14). The NMP patterns are consistent with a model of disease progression in which BPH shares many of the nuclear matrix changes observed in prostate cancer.

Antigens, Nuclear↗

Clinical efficacy of bone alkaline phosphatase and prostate specific antigen in the diagnosis of bone metastasis in prostate cancer.

PURPOSE: We investigated the usefulness of bone alkaline phosphatase isoenzyme and prostate specific antigen (PSA) determined by radioimmunoassay to predict bone scan evidence of metastasis in newly diagnosed untreated and treated prostate cancer. MATERIALS AND METHODS: We analyzed bone alkaline enzyme concentrations in 350 men, including 150 controls, 100 with benign prostatic hyperplasia and 100 with prostate cancer (52 with stages T1 to 4, M0 and 48 with stages T1 to 4, M1 to 4). We also analyzed bone alkaline phosphatase enzyme concentrations in 61 stages T1 to 4, M0 prostate cancer cases during followup after radical prostatectomy or hormonal therapy, and 17 had clinical progression (9 with local, 5 with lymph node and 3 with bone metastases). Simultaneously, we analyzed PSA concentrations. RESULTS: Average bone alkaline phosphatase enzyme levels were 12, 11.1 and 10.0 ng./ml. in the control, benign prostatic hyperplasia and stage M0 prostate cancer groups, respectively (p not significant), and 83.2 ng./ml. in patients with stage M1 to 4 disease (p<0.001). Considering that to diagnose bone metastasis the cutoff for bone alkaline phosphatase enzyme and PSA is 30 ng./ml. and 100 ng./ml., respectively, clinical effectiveness was 93.7% and 81.8%, respectively. Finally, measurement of both substances at the same time increased clinical effectiveness to 97.9%. During followup a bone alkaline phosphatase enzyme level that becomes greater than 30 ng./ml. (0% in the local and lymphatic progression groups, and 100% in the bone metastasis group) indicates the need to perform a bone scan. CONCLUSIONS: We recommend the clinical use of bone alkaline phosphatase enzyme determined by radioimmunoassay and PSA measurement for the diagnosis of bone metastases and progression of prostate cancer because of the good sensitivity and specificity.

Aged↗

Is screening for prostate cancer necessary in men with symptoms of benign prostatic hyperplasia?

In this report, we review the critical issues concerning the early detection of prostate cancer in patients presenting with symptoms of benign prostatic hyperplasia (BPH). Only with the recent introduction of serum prostate-specific antigen (PSA) testing and transrectal ultrasonography (TRUS)-guided biopsy has the question arisen to what extent the treating physician has a responsibility to rule out prostate cancer before recommending treatment-or watchful waiting-for men with clinical BPH. Uneasiness and uncertainty also result from the development of alternative therapies that do not provide tissue for pathological analysis, or alter serum PSA levels in a poorly predictable fashion. Current early detection strategies, in this clinical situation, pose unique problems, largely because of the great degree of overlap in serum PSA among men with localized prostate cancer and BPH. The underlying goal is to distinguish patients with BPH alone from those with clinically significant, but organ-confined and potentially curable prostate cancer. Treatment for prostate cancer may take precedence over BPH management strategies, while at the same time address the symptoms associated with coexistent clinical BPH. The issues discussed in this report should aid the clinician in the evaluation of patients with clinical BPH. Further studies are clearly needed that may ultimately enhance our ability to discriminate patients with clinically significant organ-confined prostate tumors from those with BPH alone.

Adult↗

Two-dimensional gel electrophoresis detects prostate-specific antigen-alpha1-antichymotrypsin complex in serum but not in prostatic fluid.

We investigated the interaction between prostate-specific antigen (PSA) and 1-antichymotrypsin (ACT) in prostatic secretions, identifying PSA and ACT in human serum, prostatic fluid, and seminal plasma by two-dimensional gel electrophoresis (2-D PAGE). Both PSA and ACT were detected in all three body fluids, but PSA-ACT complex was detected only in serum. Moreover, the 2-D PAGE Western blot staining profile for ACT from serum differed from that for prostatic fluid or seminal plasma. Incubation of prostatic fluid with purified ACT led to formation of PSA-ACT complex. Incubation of prostatic fluid with purified PSA, however, failed to form the complex, suggesting that the ACT in prostatic fluid was inactive or inhibited. Given that physiological concentrations of zinc inhibited the formation of PSA-ACT complex, we consider zinc a possible physiological inhibitor of the formation of the PSA-ACT complex. These results indicate that the failure to detect the PSA-ACT complex in prostatic fluid could be related to the inactivation of ACT, the presence of inhibitors (e.g., zinc), or simply the PSA:ACT ratio in the fluid.

Adult↗

Prostatic intraepithelial neoplasia and atypical adenomatous hyperplasia. Relationship to pathologic parameters, volume and spatial distribution of carcinoma of the prostate.

OBJECTIVE: To summarize studies that have investigated the morphologic, spatial and volumetric relationship between prostate cancer and its putative precursors, high grade prostatic intraepithelial neoplasia (HGPIN) and atypical adenomatous hyperplasia (AAH). METHODS: Studies addressing the relationship between morphologic parameters of prostate cancer (i.e., stage, grade, volume and anatomic distribution) and both HGPIN and AAH are reviewed. Similar data based on our institutional experience with surgical and autopsy series of step-sectioned, totally embedded prostate glands are also presented. RESULTS: Most investigators have demonstrated significant associations between HGPIN and carcinoma in terms of coexistence, "zonal" origin and physical proximity. The two lesions have a high tendency to be present simultaneously; both originate predominantly in the peripheral zone and are often found within the same microscopic field. Reports on the relationship between HGPIN and the stage of prostate cancer are less consistent, and the associations of this lesion with cancer grade and volume are exceedingly complex. HGPIN appears to be associated with moderately to poorly differentiated, smaller, often-multifocal tumors and is less frequent in large, high grade cancers. There are data suggesting a trend-of a reciprocal relationship between more extensive and diffuse HGPIN and large-volume prostate cancers. Conversely, there is a wide spectrum of volume distribution of the two lesions in glands harboring smaller tumors. Similar data concerning AAH are limited. CONCLUSION: There are strong and consistent data supporting various aspects of the morphologic associations between HGPIN and prostate cancer. The indications that glands harboring larger tumors tend to contain less extensive HGPIN could raise the hypothesis that as carcinoma becomes larger, it may replace areas of the gland previously occupied by HGPIN. Alternatively, prostate cancer can evolve from ducts with HGPIN and gradually overgrow their precursor. There is a relative dearth of similar information concerning AAH.

Adenoma↗