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A W Partin

Publications and source records attributed to A W Partin.

At least 145 records · Page 8Linked to original sources
PubMed1997

Incidence of high-grade prostatic intraepithelial neoplasia in sextant needle biopsy specimens.

OBJECTIVES: There is scant literature on the frequency of high-grade prostatic intraepithelial neoplasia (PIN) in needle biopsy specimens. These data have implications as to how often pathologists should be expected to diagnose these lesions on needle biopsy and impact on the feasibility of cancer chemoprevention trials for prostate cancer. METHODS: We reviewed 439 consecutive 18-gauge sextant needle biopsy specimens from the Johns Hopkins Hospital. RESULTS: Based on the pathology reports, high-grade PIN was recorded in 12 (2.7%) of the cases and was confirmed upon review. Following review of the slides, unequivocal high-grade PIN was found in an additional 6 cases. There were 6 other cases where the findings were borderline between high- and low-grade PIN, but which were believed to be more consistent with high-grade PIN. Considering these latter cases in conjunction with the unequivocal cases of high-grade PIN, the incidence of high-grade PIN was 5.5% (24 of 439). CONCLUSIONS: Recognizing that approximately 50% of men with high-grade PIN on needle biopsy will be found to have carcinoma on repeat biopsy, the management of high-grade PIN on biopsy will only apply to 50% of the men initially discovered with this finding. If only 2.75% of men who are biopsied eventually need therapy for high-grade PIN on needle biopsy, the number of cases needed to study the decrease of high-grade PIN following chemoprevention might be prohibitively high. If the incidence of high-grade PIN on needle biopsy requiring therapy is only 2.75%, it may also not be worthwhile developing large trials to investigate various treatment regimens for high-grade PIN found on biopsy.

Adult↗
PubMed1997

Percentage of free prostate-specific antigen in sera predicts aggressiveness of prostate cancer a decade before diagnosis.

OBJECTIVES: To evaluate serial measurements of free and total prostate-specific antigen (PSA) as a predictor of prostate cancer aggressiveness. METHODS: Twenty men diagnosed with adenocarcinoma of the prostate in the pre-PSA era had serum PSA measurements made on multiple stored frozen sera samples available for up to 18 years prior to diagnosis. Subjects were categorized as having aggressive cancer (n = 12) based on the presence of clinical Stage T3, or nodal or bone metastases (N+, M+), or pathologic positive-margin disease, or a Gleason score of 7 or greater; nonaggressive cancer (n = 8) was identified by the absence of these criteria. RESULTS: There was no statistically significant difference in free PSA levels among men with aggressive and nonaggressive prostate cancers from 0 to 15 years before diagnosis. Total PSA levels were significantly different between the groups by 5 years before diagnosis (P = 0.04). At a time when total PSA levels were not different between groups (10 years before diagnosis), there was a statistically significant difference in the percentage of free PSA between aggressive and nonaggressive cancers (P = 0.008). Among 14 men who had sera available for analysis at 10 years before diagnosis, all 8 men with aggressive cancers had a percent free PSA of 0.14 or less; this compares with only 2 of 6 men (33%) with nonaggressive cancer. CONCLUSIONS: These data suggest that the percentage of free PSA in sera is predictive of tumor behavior at a time when total PSA levels provide no information on tumor aggressiveness. Evaluation of the percentage of free serum PSA may be helpful in making the decision between expectant management and treatment for those men who are diagnosed with early prostate cancers by PSA testing.

Adenocarcinoma↗
PubMed1997

Detection of intact prostate cancer cells in the blood of men with prostate cancer.

OBJECTIVES: To develop a procedure to be used to find, identify, and characterize the living prostate cancer cells in the blood of patients with prostate cancer. METHODS: The procedure is based on a negative selection approach that removes most of the blood cells and collects the remaining prostate cancer cells, which are identified and characterized by fluorescent in situ hybridization with deoxyribonucleic acid probes and by indirect fluorescent immunocytochemical staining. The blood cells are removed via density gradient centrifugation. RESULTS: Using the prostate cancer LNCaP cells as a model, the recovery rate of the added prostate cancer cells to 10 mL of blood was about 85%, with a dilution of 1 LNCaP cell to 10,000 white blood cells or more. Blood samples varying from 9 to 27 mL were collected and analyzed from 8 men aged 54 to 79 years who had varying levels of PSA in serum. In one blood sample, prostate cancer cells were not found; in the seven other samples, the number of prostate cancer cells found per milliliter of blood varied from 1 to 20. Prostate cancer cells were not found in 7.5 to 15-mL blood samples from 3 healthy younger men. The prostate cells were found to be aneuploid for chromosomes 7 and 8, highly suggestive that these cells were cancerous. CONCLUSIONS: Using a negative selection approach, prostate cells can be found in the blood of patients with prostate cancer, as identified by prostate cell-specific probes and antibodies. These cells were found to be aneuploid.

Adult↗
PubMed1997

Stage D1 (T1-3, N1-3, M0) prostate cancer: a case-controlled comparison of conservative treatment versus radical prostatectomy.

OBJECTIVES: There is no consensus on the management of Stage D1 prostate cancer. The literature suggests that radical prostatectomy, as compared with pelvic lymphadenectomy (PLND) alone, may extend survival, Despite evidence that lymph node tumor burden influences cancer survival, few groups of researchers have controlled for this variable when comparing management strategies. We performed a study that was case-controlled for nodal tumor burden to determine if a survival advantage exists for radical prostatectomy. METHODS: Of 168 men with Stage D1 disease diagnosed between 1983 and 1995, 127 underwent pelvic lymphadenectomy and radical retropubic prostatectomy (PLND/RRP) and 41 underwent PLND alone. Clinical charts were reviewed for follow-up, and lymph node tumor burden was assessed by volume of nodal metastases and the percentage of positive nodes sampled. Adjuvant treatment was based on the surgeon's preference and clinical situation. Nineteen patients from each group were matched for age, PSA, Gleason score, clinical stage, follow-up, and nodal tumor burden. RESULTS: Comparison of the non-case-controlled PLND/RRP and PLND groups showed no differences in age, prostate-specific antigen level, Gleason score, clinical stage, or follow-up. The nodal tumor burden was greater for the PLND group (P = 0.001). The 10-year cancer-specific survival rates for the PLND/RRP and PLND groups were statistically different (P = 0.006). In the case-controlled group, the results were similar for cancer-specific survival at 10 years (56% and 34%, respectively; P = 0.09). CONCLUSIONS: These data suggest that in Stage D1 prostate cancer, a trend toward a statistical difference in survival may exist for radical prostatectomy as compared with conservative treatment. Further case-controlled and prospective randomized studies are needed to verify these results.

Actuarial Analysis↗
PubMed1997

Molecular forms of prostate-specific antigen and human kallikrein 2 (hK2) in urine are not clinically useful for early detection and staging of prostate cancer.

OBJECTIVES: Prostate-specific antigen (PSA), a member of the human kallikrein (hK) family, is the most important tumor marker for early detection, staging, and monitoring of men with prostate cancer today. However, the sensitivity of serum PSA is not sufficient to be used alone for prostate cancer screening. Recently, it was reported that the serum-to-urinary total PSA ratio improves the detection of men with prostate cancer, especially in men with a serum total PSA level between 4.0 and 10.0 ng/mL. We tested this hypothesis by evaluating the clinical usefulness of this PSA ratio as well as the use of the different molecular forms of PSA and human kallikrein 2 (hK2) in urine for detection and staging of prostate cancer. METHODS: One hundred ten fresh, midstream urine specimens (prostate cancer 62, benign prostatic hyperplasia [BPH] 38, healthy male control 5, women 5) were collected. Serum total PSA, urine total PSA, urinary free PSA, urinary alpha 1-antichymotrypsin-bound PSA, and urinary hK2 levels were determined by monoclonal antibody assays (Hybritech Inc.). The serum-to-urinary total PSA ratio was calculated. RESULTS: The serum-to-urinary total PSA ratio did not accurately distinguish between men with BPH and men with prostate cancer. There was no significant difference between the urinary levels of any of the molecular forms of PSA or hK2 between men with prostate cancer and men with BPH. Among men with prostate cancer, neither urinary hK2 nor urinary levels of any of the molecular forms of PSA correlated with age, pathologic stage, or Gleason grade. CONCLUSIONS: In our study, the serum-to-urinary total PSA ratio did not improve the detection of men with prostate cancer. Furthermore, measurement of the molecular forms of PSA and hK2 in urine did not improve the detection or staging of prostate cancer over serum PSA alone.

Aged↗
PubMed1997

Preliminary immunohistochemical characterization of a monoclonal antibody (PRO:4-216) prepared from human prostate cancer nuclear matrix proteins.

OBJECTIVES: A nuclear matrix protein (PC-1) was previously identified and reported to be present only in human prostate cancer but absent in tissue from the same prostate containing either benign prostatic hyperplasia (BPH) or normal prostate tissue. The PC-1 protein was identified by high resolution two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and exhibited a molecular mass of 56 kDa and an isoelectric point of 6.58. This work investigates the immunohistochemical characterization of PRO:4-216, a monoclonal antibody to PC-1. METHODS: Areas of the 2D-PAGE gels containing the human prostate cancer nuclear matrix proteins near PC-1 were isolated, eluted, and injected into mice to develop monoclonal antibodies. Antibodies were screened by immunofluorescence for nuclear reactivity to a human prostate cancer cell line (LnCaP) and by 1D and 2D Western blots for reactivity with prostate cancer nuclear matrix proteins. Monoclonal antibodies from the selected clones were affinity purified. The monoclonal antibody PRO:4-216 was used to analyze frozen tissue from 20 cancerous, 22 BPH, and 22 normal regions from fresh human prostate specimens. Tissue sections were analyzed for their immunohistochemical (IHC) (horseradish peroxidase) staining. RESULTS: Using a reference value for positive staining at an IHC score of greater than 50, 85% (17 of 20) of the cancerous, 5% (1 of 22) of the BPH, and 9% (2 of 22) of the normal prostate tissues stained positive. The one BPH and two normal tissues that stained positive were taken from prostates in which the adjacent cancerous tissue also demonstrated high IHC scores (greater than 225). CONCLUSIONS: These data demonstrate nuclear reactivity on fresh frozen human prostate cancer tissue for the monoclonal antibody PRO:4-216. PRO:4-216 may aid in distinguishing normal prostate and BPH from cancerous tissue.

Animals↗
PubMed1997

Prostate-specific antigen after anatomic radical retropubic prostatectomy. Patterns of recurrence and cancer control.

In a series of 1623 men with a follow-up of 5 +/- 3 years (range 1-13) after anatomic RRP for clinically localized prostate cancer, 17% (276/1623) have shown recurrence. A detectable PSA was the only evidence of recurrence in 7.9%, whereas 2.5% have recurred locally and 5.4% have developed distant metastases. The overall actuarial progression-free rate for these men at 10 years was 68%. Actuarial rates at 10 years were 18% for development of an isolated PSA recurrence, 8% for local recurrence, and 9% for distant recurrence. The actuarial likelihood of a postoperative recurrence increased with increasing clinical stage, Gleason score, preoperative PSA level, and pathologic stage. Although not shown in our previous report, the actuarial rate of recurrence of tumors with a Gleason score of 7 was statistically different from that of tumors of higher Gleason score (8-10). As well, men with preoperative PSA levels of 10.1 to 20 ng/mL experienced recurrence at a significantly lower rate than did men with preoperative PSA levels greater than 20 ng/mL. By using a combination of Gleason score, pathologic stage, and surgical margin status, we demonstrated that the presence of a positive surgical margin did not dramatically affect recurrence in tumors of Gleason scores 2 to 6 with capsular penetration. Surgical margin status was important in high-grade tumors with capsular penetration. In fact, tumors with capsular penetration, Gleason score of at least 7, and a positive surgical margin behaved similarly to tumors with invasion of the seminal vesicles. Preservation of potency did not adversely influence cancer control. The Gleason score, presence or absence of seminal vesicle or lymph node involvement, and the timing of PSA recurrence are all important variables in predicting eventual local versus distant failure associated with an isolated rise in serum PSA. Overall actuarial cause-specific survival at 5 and 10 years was 99% and 93%. Although there was no difference in survival among men grouped by TNM stage or preoperative PSA, advancing histologic grade and pathologic stage did have an effect on actuarial cause-specific survival. Men undergoing RRP for clinically localized prostate cancer showed a 16% actuarial rate of development of metastatic disease at 10 years. This is considerably better than conservative therapy and justifies RRP as the treatment of choice for men with clinically localized disease who are otherwise healthy and have a greater than 10-year life expectancy.

Disease Progression↗
PubMed1997

Clinical and biological characteristics of familial benign prostatic hyperplasia.

PURPOSE: We attempted to determine the clinical and biological characteristics of familial benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Urinary flow rate, prostate size, symptom score, serum prostate specific antigen, testosterone and dihydrotestosterone were measured in subjects who participated in the nationwide Merck phase III finasteride clinical trial. Findings in the 69 men with familial BPH (3 or more family members with BPH, including the proband) were compared to those in the 345 with no family history of BPH. Logistic regression was used to detect relationships between familial BPH, and these variables before and after 5 alpha-reductase inhibition with finasteride. RESULTS: Familial BPH was characterized by large prostate size. Mean prostate volume in men with familial and sporadic BPH was 82.7 and 55.5 ml., respectively (p < 0.001). Other clinical findings, including serum androgen levels and response to finasteride, were similar in familial and sporadic BPH. The frequency of familial BPH in patients with prostate size in the largest and smallest deciles was 46 and 13%, respectively. CONCLUSIONS: Familial BPH in this group of patients was associated with large prostate size, normal serum androgen levels and normal response to 5 alpha-reductase inhibition. A genetic factor responsible for familial BPH may exert its influence through androgen independent control of prostatic growth.

5-alpha Reductase Inhibitors↗
PubMed1997

Prostate tissue composition and response to finasteride in men with symptomatic benign prostatic hyperplasia.

PURPOSE: We sought to quantify prostate tissue changes induced by finasteride and to identify a predictor of finasteride response in men with symptomatic benign prostatic hyperplasia (BPH) via a randomized, placebo controlled, double-blind clinical trial. MATERIALS AND METHODS: Men with symptomatic BPH (52 to 78 years old) were randomly assigned to 6 months of treatment with finasteride (26) or placebo (15). Outcome measures were clinical (urinary symptom score and flow rate), chemical (serum prostate specific antigen and dihydrotestosterone levels), volumetric (transrectal ultrasound, and magnetic resonance imaging for whole and zonal prostate volumes) and histological (morphometry of prostate sextant biopsies, separated into inner and outer gland segments, to measure the percent epithelium, stroma and glandular lumen). RESULTS: In the finasteride group we found a suggestion of decreasing symptom scores and increasing flow rates (not significant) with significant decreases (p < 0.01) in prostate specific antigen (48%), dihydrotestosterone (74%) and prostate volume (21%). Finasteride treatment induced a 55% decrease in inner gland epithelium (p < 0.01) with little effect on stroma or lumina. We also found a linear correlation between pretreatment inner gland epithelial content and prostate volume decrease induced by the drug (tau = 0.58, p = 0.01). CONCLUSIONS: Finasteride treatment results in a major suppression of prostate epithelium, which is most pronounced in the inner gland. Moreover, a finasteride induced prostate volume decrease was predictable by quantification of epithelial tissues of the inner gland. These data lend additional support to the emerging concept of transition zone primacy in symptomatic BPH.

Aged↗
PubMed1997

Prostate-specific antigen: what's new in 1997.

When used alone, prostate-specific antigen (PSA) is not sufficiently sensitive or specific to consider it an ideal tool for the early detection or staging of prostate cancer. To optimize the use of PSA, the concepts of PSA velocity, PSA density, and age-related PSA values were developed. Although PSA velocity provides excellent results, its determination requires three PSA values over a 2-year period. The value of PSA density rests on the accurate determination of prostatic volume by transurethral ultrasound (TRUS), which is examiner-dependent. Age-specific reference ranges appear to be more sensitive in men under age 60 than in those over 60. The molecular forms of PSA, especially the percentage of free PSA, seem to be useful tools for the detection of prostate cancer in men with slightly elevated total PSA. New molecular techniques, such as the reverse transcriptase-polymerase chain reaction (RT-PCR), enable the detection of minimal amounts of PSA messenger RNA (mRNA). Human kallikrein 2 (hK2), a serine protease closely related to PSA that also is expressed predominantly in the prostate, may be a new marker for prostate cancer.

Biomarkers, Tumor↗
PubMed1996

Telementoring of laparoscopic procedures: initial clinical experience.

BACKGROUND: To assess the feasibility of telementoring, a clinical telepresence system was developed. METHODS: Telementoring was attempted in 14 advanced and 9 basic urologic laparoscopic procedures. The remote surgeon located in a control room (> 1,000 feet from operating room) supervised an inexperienced surgeon. Mentoring was accomplished with real-time video images, two-way audio communication, a robotic arm used to control the videoendoscope, and a telestrator. The patient outcome, complications, and operative time were assessed and compared to patients undergoing matched procedures in which the experienced surgeon was working side by side with the primary surgeon. RESULTS: The overall telementoring success rate was 95.6% (22/23 cases) with no increase in complications. Telementoring of a laparoscopic radical nephrectomy failed secondary to improper positioning of the robotic arm. Operative times compared between telementored and traditionally mentored procedures were not statistically different for basic procedures but were longer for advanced cases. CONCLUSIONS: Telementoring of laparoscopic procedures is safe and feasible. Further clinical studies are needed prior to implementing telementoring in surgical training.

Education, Medical↗
PubMed1996

Neuroendocrine differentiation in prostate cancer: enhanced prediction of progression after radical prostatectomy.

It is controversial whether neuroendocrine (NE) differentiation in adenocarcinoma of the prostate is associated with more aggressive behavior. Most studies included patients with tumors of a wide range of grades and stages and an end point of disease-specific survival, a relatively insensitive marker of progression. The authors studied completely embedded radical prostatectomy specimens from 104 patients with clinically organ-confined carcinoma and no history of adjuvant or neoadjuvant therapy. Progression was marked by a serum prostate-specific antigen (PSA) concentration greater than or equal to 0.2 ng/mL. Seventy-six men did not progress, with a mean follow-up period of 8.0 years (range = 7 to 10 years). Forty-eight men progressed at a mean time after surgery of 3.6 years (range = 1 to 8 years). Twenty-one percent of the tumors were organ confined: 79% had capsular penetration. Seminal vesicles and lymph nodes were negative in all cases. A representative section through the main tumor mass was stained for chromogranin A. Reactive neoplastic cells were counted subjectively as well as individually enumerated. Gleason grade, pathological stage, and degree of NE differentiation all correlated with progression. Only grade and extent of NE differentiation predicted progression in a multivariate analysis. NE differentiation did not correlate with stage or grade. Extent of NE differentiation separated patients (59 cases) with tumors of Gleason sum less than or equal to 6 into groups with high and low risks for progression (P < .008) independent of Gleason sum. Extent of NE differentiation provides prognostic information in addition to that provided by grade in cases of early prostate cancer treated by radical prostatectomy.

Cell Differentiation↗
PubMed1996

Anatomic approach for placement of surgical drains after radical retropubic prostatectomy: long-term effects on postoperative pain.

OBJECTIVES: The placement of drains following radical retropubic prostatectomy (RRP) may potentially damage neural and vascular structures within the abdominal wall, leading to postoperative pain and morbidity. In this study, we compare postoperative pain in two groups of men who underwent RRP. The Davol drains were either placed lateral to the rectus muscle (n = 100) or in the medial two thirds of the rectus muscle (n = 100). METHODS: We investigated postoperative pain for an average of 5 months after RRP. Detailed responses were obtained from 89.5% (179 of 200) of the men. The average age was 57 years and the average follow-up 20 weeks. RESULTS: Overall, 33.5% (60 of 179) of the men reported postoperative pain associated with either the incision or drain site. Rated on a scale of 0 to 10 (with 10 representing the most pain), the average pain scale assessment was 1.3 +/- 2.6 (range 0 to 6). Pain was attributable to the incision site only in 9% (16 of 179) and at the drain site only in 24% (42 of 179). We found more pain overall (41%) where the drains were placed lateral to the rectus muscle as compared with men in whom the drains were placed in the medial two thirds of the rectus muscle (26%) (P = 0.03). CONCLUSIONS: Placement of drains in the medial two thirds of the rectus muscles avoids injury to intercostal nerves and results in less pain at the drain sites.

Drainage↗
PubMed1996

Histopathologic characterization of hereditary benign prostatic hyperplasia.

OBJECTIVES: Recent studies suggest the presence of a hereditary form of benign prostatic hyperplasia (H-BPH). This study was undertaken to characterize the histopathologic features of BPH in these men. METHODS: Because study subjects with H-BPH were young (mean age 59 years) and had a large prostate (mean prostate weight 61 g), we compared the histopathologic findings in these men with those in two different control groups: (1) age-matched control subjects (mean age 59 years; mean prostate weight 31 g), and (2) prostate weight-matched control subjects (mean age 70 years; mean prostate weight 61 g). Using a color video image analysis system, we morphometrically determined stromal/epithelial ratios in histologic sections taken from 12 men with H-BPH, 36 age-matched control subjects, and 36 prostate weight-matched control subjects. RESULTS: The stromal/epithelial ratio was 2.6 +/- 1.4 in the men with H-BPH, 2.7 +/- 1.7 in the age-matched control subjects, and 1.7 +/- 0.9 in the prostate weight-matched control subjects. Regression analysis, which controlled for the differences in prostate weight or patient age between men with H-BPH and age-matched and prostate weight-matched control subjects, respectively, revealed a significant difference between men with H-BPH and prostate weight-matched control subjects (P = 0.015) but no difference from age-matched control subjects (P = 0.36). CONCLUSIONS: The larger prostates in young men with H-BPH are characterized by a higher stromal/epithelial ratio than are similar-sized prostates in older men with sporadic BPH. This finding gives rise to speculation that H-BPH is associated with an increase in stromal elements.

Adult↗
PubMed1996

Ability to predict biochemical progression using Gleason score and a computer-generated quantitative nuclear grade derived from cancer cell nuclei.

OBJECTIVES: To determine the ability to predict prostate cancer progression using shape, size, and chromatin texture nuclear grading features preselected by logistic regression analyses based on expert-selected prostate cancer cell nuclei captured using a computer-assisted image analysis system. METHODS: One hundred fifteen patients with clinically localized prostate cancer were identified at the Johns Hopkins medical institutions. The mean follow-up period was 10.4 +/- 1.7 years in 70 patients without disease progression, whereas the mean time to progression for the entire group was 3.8 +/- 2.5 years. Using 5-microns Feulgen-stained tissue sections, approximately 150 cancer cell nuclei were selected and captured for each case using a CAS-200 Image Analysis System. Thirty-eight different nuclear morphometric descriptors (NMDs) were calculated for each cell nucleus. The variance of the NMDs for each tumor was examined by univariate and multivariate logistic regression analyses and by Cox survival analyses to assess their ability to predict prostate cancer progression. RESULTS: Postoperative Gleason scoring was significantly correlated with disease progression (P < 0.00001; sensitivity, 73%; specificity, 84%; receiver operating characteristic curve area under the curve (ROC-AUC), 83%). Using backward stepwise logistic regression at a stringency of P < 0.05, the variances of 11 of the NMDs were found to be multivariately significant for progression prediction (P < 0.00001; sensitivity, 78%; specificity, 83%; ROC-AUC, 86%). A single value, termed the quantitative nuclear grade (QNG), was created from the variances of these, 11 multivariately significant NMDs using the logistic regression function. The QNG and the postoperative Gleason score were combined to create a model for the prediction of progression having a sensitivity of 89%, specificity of 84%, and ROC-AUC of 92%. These two parameters (QNG and Gleason score) clearly separated the patient sample into three statistically distinct risk groups and predicted the time to progression on the basis of Kaplan-Meier survival probability analysis. CONCLUSIONS: The QNG, combined with the postoperative Gleason score, may assist in the more accurate stratification of patients undergoing radical prostatectomy into low-, moderate-, and high-risk groups for cancer recurrence and may permit the early initiation of adjuvant therapy.

Adult↗
PubMed1996

Longitudinal analysis of serial measurements of free and total PSA among men with and without prostatic cancer.

OBJECTIVES: Evaluation of free and total serum prostate specific antigen (PSA) levels before diagnosis of prostate cancer. METHODS: Free and total PSA levels were measured on frozen sera samples of 26 men with no history of prostate disease (controls), 29 men with a histologic diagnosis of benign prostatic hyperplasia (BPH) made at simple prostatectomy (BPH cases), and 23 men with a histologic diagnosis of prostatic cancer (cancer cases). Longitudinal regression analysis was used to evaluate PSA levels as a function of years before diagnosis of prostate disease. RESULTS: On average, mean total serum PSA was statistically significantly greater for subjects with cancer (5.0 ng/mL +/- 0.9) versus BPH (2.8 ng/mL +/- 0.3) and control subjects (0.8 ng/mL +/- 0.1) by 4 years before diagnosis, whereas free PSA levels were similar among groups at 4 years before diagnosis. The ratio of free to total serum PSA continuously decreased among cancer cases over the decade before cancer diagnosis. At a time when mean total and free PSA levels were similar among groups (8 years before diagnosis), the ratio of free to total PSA was statistically significantly lower for cancer cases (0.13 +/- 0.01) compared with BPH (0.17 +/- 0.01) and control cases (0.21 +/- 0.02). Use of a free to total PSA ratio of < or = 0.12 when total PSA was between 4.0 and 10.0 ng/mL resulted in the highest sensitivity (76%) and specificity (94%) for diagnosis among subjects with and without cancer. Lowering the reflex range to 2.5 ng/mL increased false positive tests more than it increased sensitivity. CONCLUSIONS: The ratio of free to total PSA is the earliest serum marker predicting a subsequent diagnosis of prostate cancer. Measurement of the free to total serum PSA ratio would appear to reduce false positive results among men without prostate cancer.

Aged↗