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W J Catalona

Publications and source records attributed to W J Catalona.

At least 19 recordsLinked to original sources

Quality-of-life outcomes for men with prostate carcinoma detected by screening.

BACKGROUND: There is limited information on outcomes of prostate carcinoma treatments given to screened patient populations for whom cancer is usually detected at an earlier stage. METHODS: The authors conducted a cross-sectional evaluation of quality-of-life outcomes for men with prostate carcinoma detected in screening studies at a university center. Of 2234 men diagnosed with prostate carcinoma between 1989 and 1997, 74% responded to the questionnaire. Primary management included radical prostatectomy (76%), radiotherapy (11%), observation (7%), hormonal therapy (4%), and cryoablation (2%). Main outcome measures included validated measurements of quality of life, urinary and sexual functioning, and bother (36-item RAND Health Survey, UCLA Prostate Cancer Index). RESULTS: After controlling for demographic factors, differences among treatment groups were found for all general quality-of-life outcomes, with increased impairment in men who underwent hormonal therapy (all P values <0.05). Urinary and sexual function and bother were also significantly related to treatment. However, among men followed for > or =12 months, only 9% reported a moderate or major problem with urinary control. Sexual functioning was a moderate or major problem following treatment for 58% treated with prostatectomy, 48% treated with radiotherapy, 64% treated with hormonal therapy, 45% treated with cryoablation, and 30% managed with observation. Approximately one-third of the men younger than 70 years who underwent radical prostatectomy maintained adequate sexual functioning posttreatment. CONCLUSIONS: Up to 6 years after diagnosis, the majority of men with prostate carcinoma detected by screening were bothered by their current sexual function, regardless of treatment. In contrast, most men were not bothered by their current urinary function.

Age Factors

Primary treatment choices for men with clinically localized prostate carcinoma detected by screening.

BACKGROUND: Increasingly, prostate carcinoma is diagnosed through screening. However, little is known regarding factors that influence a patient's decision concerning the treatment choices presented to him. METHODS: Subjects were prostate carcinoma patients detected through the Washington University PSA Prostate Cancer Screening Program between September 1989 and June 1998. The sources of data were the prostate specific antigen (PSA) screening database and follow-up questionnaire. RESULTS: Among 1809 study subjects, 79.2% chose radical prostatectomy (RP), 12.4% chose radiation therapy, and 8.4% chose watchful waiting (WW) as their decision regarding primary treatment. In bivariate analyses, education, income, age, indication for prostate biopsy, comorbidity score, serum PSA level, clinical stage, and pretreatment urinary and sexual function were associated significantly with treatment choice, but race, marital status, and Gleason grade were not. In a multivariate analysis, age, race, clinical stage, PSA level, and pretreatment urinary and sexual function were found to be associated significantly with treatment choice. For every 5-year decrease in age, the odds for choosing RP versus WW increased by 276%; for every 1-ng increase in PSA, the odds for choosing RP versus WW increased by 12%. Non-African-American patients were greater than four times more likely to select RP versus WW. Patients with T2 tumors and those with normal pretreatment urinary function were three times more likely and twice more likely to choose RP versus WW, respectively. CONCLUSIONS: In the current study, RP was the most widely used treatment in patients with screen-detected prostate carcinoma. Age, race, PSA level, clinical stage, and pretreatment urinary and sexual function were significant factors influencing treatment selection.

Aged

Percentage of free PSA in black versus white men for detection and staging of prostate cancer: a prospective multicenter clinical trial.

OBJECTIVES: In predominately white populations, measurement of the percentage of free prostate-specific antigen (%fPSA) has been shown to enhance the specificity of total PSA testing for prostate cancer while maintaining high sensitivity and to aid in prostate cancer staging. This study evaluated whether the %fPSA cutoff that maintained a 95% sensitivity in a white population yielded the same sensitivity and specificity in a black population and whether %fPSA was useful in predicting postoperative pathologic features in blacks. METHODS: We evaluated 647 white and 79 black men, prospectively enrolled at prostate cancer screening and surgical referral centers. Subjects were 50 to 75 years old with digital rectal examination findings that were not suspicious for prostate cancer and total PSA values between 4.0 and 10.0 ng/mL. All had undergone needle biopsy of the prostate. Hybritech's Tandem total and free PSA assays were used. RESULTS: Ninety-five percent sensitivity was attained with a %fPSA cutoff of 25% in both races. Use of this cutoff could have avoided unnecessary biopsies in 20% of white and 17% of black subjects (P = 0.69). In receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) for %fPSA was significantly higher than for total PSA in both blacks (0.76 versus 0.56, P <0.01) and whites (0.70 versus 0.54, P <0.001). In both races, higher %fPSA values indicated a lower risk of cancer and also predicted favorable pathologic features in radical prostatectomy specimens. CONCLUSIONS: A 25% fPSA cutoff detected 95% of cancers and reduced unnecessary biopsies in both races. Higher %fPSA values were associated with favorable postoperative histopathologic findings in both races.

Aged

A genome screen of multiplex sibships with prostate cancer.

Analysis of a genome screen of 504 brothers with prostate cancer (CaP) who were from 230 multiplex sibships identified five regions with nominally positive linkage signals, on chromosomes 2q, 12p, 15q, 16p, and 16q. The strongest signal in these data is found on chromosome 16q, between markers D16S515 and D16S3040, a region suspected to contain a tumor-suppressor gene. On the basis of findings from previous genome screens of families with CaP, three preplanned subanalyses were carried out, in the hope of increasing the subgroup homogeneity. Subgroups were formed by dividing the sibships into a group with a positive family history (FH+) that met criteria for "hereditary" CaP (n=111) versus those which did not meet the criteria (n=119) and by dividing the families into those with a mean onset age below the median (n=115) versus those with a mean onset age above the median (n=115). A separate subanalysis was carried out for families with a history of breast cancer (CaB+ [n=53]). Analyses of these subgroups revealed a number of potentially important differences in regions that were nonsignificant when all the families were analyzed together. In particular, the subgroup without a positive family history (FH-) had a signal in a region that is proximal to the putative site of the HPC1 locus on chromosome 1, whereas the late-age-at-onset group had a signal on 4q. The CaB+ subgroup revealed a strong linkage signal at 1p35.1.

Age of Onset

Pain and morbidity of transrectal ultrasound guided prostate biopsy: a prospective randomized trial of 6 versus 12 cores.

PURPOSE: An increasing number of studies suggest that 6-sector transrectal ultrasound guided biopsy of the prostate provides insufficient material to detect all clinically important prostate cancers and more cores may improve detection rates. We performed a prospective, randomized study to determine the effect of increasing the number of cores from 6 to 12 on pain and other morbidity associated with the biopsy procedure. MATERIALS AND METHODS: A total of 160 men (44 black, 28%) with a mean age plus or minus standard deviation of 65+/-8 years who had serum prostate specific antigen between 2.5 and 20.0 ng./ml. and/or digital rectal examination findings suspicious for cancer were prospectively randomized to undergo 6 or 12-core biopsy. Patients completed a self-administered questionnaire addressing pain and other morbidity before, and immediately and 2 and 4 weeks after biopsy. RESULTS: There was no difference between groups in mean pain scale with time for abdominal and rectal pain. For probe insertion, needle insertion and overall pain there was a significant increase in pain recalled at 2 which persisted at 4 weeks compared to immediately after biopsy. However, there was no difference for these 3 post-biopsy pain measures between the 6 and 12-core groups. In the 12-core group there was a statistically significant increase in hematochezia and hematospermia (24% versus 10%, p = 0.04 and 89% versus 71%, p = 0.01, respectively) but no significant difference between groups reporting morbidity as a moderate or major problem. There was no significant change in International Prostate Symptom Score, fever or hospitalization in the 12-core group. CONCLUSIONS: The 12-core prostate biopsy procedure is generally well tolerated and can be safely performed with no significant difference in pain or morbidity compared to the 6-core procedure.

Aged

Use of percentage of free prostate-specific antigen to identify men at high risk of prostate cancer when PSA levels are 2.51 to 4 ng/mL and digital rectal examination is not suspicious for prostate cancer: an alternative model.

OBJECTIVES: Currently, many clinicians do not recommend prostate biopsy for men with digital rectal examination (DRE) results that are not suspicious for cancer and prostate-specific antigen (PSA) values between 2.51 and 4 ng/mL. We propose a new model for the detection of prostate cancer using the percentage of free PSA (%FPSA) in the limited range of PSA values between 2.51 and 4 ng/mL that maximizes clinical specificity (ie, minimizes false-positive results). This model identifies higher risk patients in this relatively low-risk population. METHODS: Three hundred sixty-eight archived serum samples from men evaluated and treated at two academic institutions were reviewed. All men had a histologic diagnosis, findings not suspicious for cancer on DRE, and PSA levels between 2.51 and 4 ng/mL. Samples were tested in Hybritech's Tandem-R PSA and Tandem-R free PSA (FPSA) assays in the same laboratory at each institution. RESULTS: Various models for cancer detection using %FPSA when PSA is 2.51 to 4 ng/mL and DRE is not suspicious for cancer are proposed. These models recommend biopsy for only 10% to 36% of the men in this population and would identify as many as 30% to 54% of the detectable cancers. There is evidence that the cancers that would be detected are the most aggressive cancers in this population. CONCLUSIONS: Our models identified men with a higher risk of prostate cancer in a relatively low-risk population that currently does not routinely undergo biopsy. This may allow for a more cost-effective way to increase cancer detection when PSA values are between 2.51 and 4 ng/mL and DRE is not suspicious for cancer. This model has the potential to detect a greater number of clinically important and potentially curable cancers than would be detected with current practice.

Aged

Use of human glandular kallikrein 2 for the detection of prostate cancer: preliminary analysis.

OBJECTIVES: Human glandular kallikrein 2 (hK2) and prostate-specific antigen (PSA) are members of a multigene family of serine proteases that share approximately 80% sequence homology. Both are expressed in the prostate epithelium, are under androgen regulation, are present in serum and seminal fluid, and can form complexes with endogenous protease inhibitors (eg, alpha2-macroglobulin and alpha1-antichymotrypsin). Differences in immunohistochemistry and substrate specificity suggest hK2 may provide unique information for early detection and characterization of prostate cancer. METHODS: Nine hundred thirty-seven archived serum samples from men treated at two academic institutions were studied. All men underwent biopsy, had a histologically confirmed diagnosis of cancer or noncancer, and a total PSA level greater than 2 ng/mL. Samples were tested in Hybritech's Tandem-R PSA and Tandem-R free PSA (fPSA) assays and a research prototype assay for total hK2 (thK2). RESULTS: The thK2/fPSA ratio provided additional specificity for cancer detection over PSA and the percentage of fPSA (%fPSA). A model for cancer detection using %fPSA and the thK2/fPSA ratio when PSA is 2 to 4 ng/mL is proposed that would identify as many as 40% of the cancers and would require biopsy in only 16.5% of the men in this PSA range. CONCLUSIONS: In this study, %fPSA and thK2/fPSA provided unique information for prostate cancer detection and increased the specificity of cancer detection.

Aged

A prospective randomized comparison of three blood conservation strategies for radical prostatectomy.

BACKGROUND: Preoperative autologous blood donation is a standard of care for elective surgical procedures requiring transfusion. The authors evaluated the efficacy of alternative blood-conservation strategies including preoperative recombinant human erythropoietin (rHuEPO) therapy and acute normovolemic hemodilution (ANH) in radical retropubic prostatectomy patients. METHODS: Seventy-nine patients were prospectively randomized to preoperative autologous donation (3 U autologous blood); rHuEPO plus ANH (preoperative subcutaneous administration of 600 U/kg rHuEPO at 21 and 14 days before surgery and 300 U/kg on day of surgery followed by ANH in the operating room); or ANH (blinded, placebo injections per the rHuEPO regimen listed previously). Transfusion outcomes, perioperative hematocrit levels, postoperative outcomes, and blood-conservation costs were compared among the three groups. RESULTS: Baseline hematocrit levels were similar in all groups (43%+/-2%). On the day of surgery hematocrit decreased to 34% +/-4% in the preoperative autologous donation group (P < 0.001), increased to 47%+/-2% in the rHuEPO plus ANH group (P < 0.001), and remained unchanged at 43%+/-2% in the ANH group. Allogeneic blood exposure was similar in all groups. The rHuEPO plus ANH group had significantly higher hematocrit levels compared with the other groups throughout the hospitalization (P < 0.001). Average transfusion costs were significantly lower for ANH ($194+/-$192) compared with preoperative autologous donation ($690+/-$128; P < 0.001) or rHuEPO plus ANH ($1,393+/-$204, P < 0.001). CONCLUSIONS: All three blood-conservation strategies resulted in similar allogeneic blood exposure rates, but ANH was the least costly technique. Preoperative rHuEPO plus ANH prevented postoperative anemia but resulted in the highest transfusion costs.

Aged

Correlates of dissatisfaction with treatment in patients with prostate cancer diagnosed through screening.

PURPOSE: We evaluated correlates of patient reported dissatisfaction with treatment of prostate cancer detected by screening. MATERIALS AND METHODS: We performed a cross-sectional retrospective study to evaluate the correlates of dissatisfaction with treatment in 1,651 patients in whom prostate cancer was detected through serial screening. We included demographic and clinical characteristics in the independent and control variables, and we validated measurements of quality of life outcomes. RESULTS: Overall 11% of patients were dissatisfied with the treatment received. Differences in the rates of dissatisfaction with treatment were not statistically significant across treatment groups (11% for retropubic radical prostatectomy, 21% for perineal radical prostatectomy, 14% for radiotherapy, 8% for observation, 8% for hormonal treatment and 4% for cryoablation, p = 0.1). Patient age, race, followup interval, marital status, education and co-morbid conditions were not significant correlates of dissatisfaction with treatment (for all characteristics p> or =0.05). Urinary function and bothersomeness were associated with dissatisfaction with treatment (p<0.0001), whereas sexual function and bothersomeness were not (p>0.05). Multivariate analysis revealed that urinary function and bothersomeness were also the only significant correlates of dissatisfaction with treatment. CONCLUSIONS: Of patients in whom prostate cancer was detected by screening 11% were dissatisfied with treatment. Urinary function and bothersomeness were the only important correlates of dissatisfaction.

Aged

Digital rectal examination for detecting prostate cancer at prostate specific antigen levels of 4 ng./ml. or less.

PURPOSE: We evaluated the detection rate of prostate cancer in men with suspicious digital rectal examination findings and serum prostate specific antigen (PSA) 4 ng./ml. or less. We also evaluated the stage and grade of cancers detected. MATERIALS AND METHODS: We screened 22,513 community volunteers by PSA testing and digital rectal examination at 6-month intervals. Biopsy was recommended when either test was suspicious for cancer. In the subset of 2,703 white and black men in whom PSA was 4 ng./ml. or less and digital rectal examination was suspicious for prostate cancer we compared compliance with biopsy recommendations, cancer detection rates, and stage and grade of cancers detected. We then correlated these results with patient age, race and serum PSA concentration. We performed multivariate logistic regression analysis to predict cancer based on clinical characteristics, and evaluated the positive predictive value of digital rectal examination for detecting cancer as stratified by race and PSA. RESULTS: Of the men 70% underwent biopsy with no difference in compliance according to age, race or PSA level. The 13% cancer detection rate correlated with age, race and PSA (p <0.003). The positive predictive value of a suspicious digital rectal examination was 5, 14 and 30% in men with PSA 0 to 1.0, 1.1 to 2.5 and 2.6 to 4.0 ng./ml., respectively. All cancers were clinically localized. Of the 72% of cases that were surgically staged 82% were organ confined and 78% were moderately differentiated. CONCLUSIONS: The positive predictive value of suspicious digital rectal examination was appreciable in men with low serum PSA. The majority of cancer cases detected by digital rectal examination had features of clinically important and potentially curable disease.

Aged

Retrospective comparison of radical retropubic prostatectomy and 125iodine brachytherapy for localized prostate cancer.

PURPOSE: Favorable results with 125iodine (I) brachytherapy have been reported in select patients with localized prostate cancer. We evaluate the results of radical prostatectomy in patients matched for similar pretreatment clinicopathological characteristics. MATERIALS AND METHODS: From May 1983 to April 1998, 1 surgeon (W. J. C.) performed radical retropubic prostatectomy in 1,952 men (mean age plus or minus standard deviation 63+/-7 years), of whom 1,364 had Gleason score 6 or less on preoperative needle biopsy, a preoperative serum prostate specific antigen (PSA) value available and clinical stage T1 or T2 disease. We categorized all patients by preoperative Gleason score, preoperative PSA and clinical stage. For each Gleason score-by-PSA stratum we randomly selected by computer the number of men necessary to achieve the same overall distribution of clinical characteristics as in a series of patients treated with brachytherapy. All men were followed with semiannual PSA measurements and annual digital rectal examinations. Serum PSA greater than 0.3 ng/ml was considered evidence of cancer recurrence. Simple univariate statistics were used to compare clinical characteristics between series, and 7-year recurrence-free survival was estimated using Kaplan-Meier product limit estimates. To avoid a possible chance extreme result from 1 random sample we estimated 7-year recurrence-free survival in 5 computer selected random samples of our population. RESULTS: Mean 7-year recurrence-free survival was 84% (95% confidence intervals 78 to 89) for the radical prostatectomy series compared to 79% (confidence intervals not provided) for the 125I brachytherapy series. CONCLUSIONS: Radical prostatectomy yielded a proportionately but not statistically significant higher 7-year probability of nonprogression than 125I brachytherapy in patients with favorable clinicopathological characteristics. Comparisons are confounded by residual differences in clinicopathological features of tumors between groups and different treatment end points to determine outcomes. Further prospective, randomized clinical trials are required for valid comparisons.

Brachytherapy

Clinical and pathological characteristics, and recurrence rates of stage T1c versus T2a or T2b prostate cancer.

PURPOSE: We compare clinicopathological features, and cancer recurrence and survival rates in men with stage T1c versus T2a or T2b prostate cancer. MATERIALS AND METHODS: From 1988 through 1998, 1 surgeon (W. J. C.) performed radical retropubic prostatectomy in 1,620 men with a mean age plus or minus standard deviation of 62.3 +/- 7 years. Clinical stage was T1c in 39%, T2a in 22% and T2b in 39% of patients. Patients were followed with semiannual prostate specific antigen (PSA) measurement and annual digital rectal examination. Serum total PSA greater than 0.3 ng./ml., histologically confirmed local tumor recurrence or distant metastases were considered evidence of cancer recurrence. Simple univariate statistics were used to compare clinical and pathological features by clinical stage, and multivariate Cox models were used to compare 5-year recurrence-free probabilities . The 5-year all cause and disease specific survival rates were calculated using Kaplan-Meier product limit estimates. RESULTS: Mean patient age was younger for the clinical stage T1c group (61 years) than for the T2a (62 years) or T2b (64 years) group. Mean preoperative PSA and the percentage of patients with biopsy Gleason score 8 to 10 were more favorable for the T1c (8 ng./ml., 3%) and T2a (7, 5%) groups than for the T2b group (11, 6%). Cancerous surgical margins, seminal vesicle invasion and lymph node metastases were also less frequent in the T1c (20, 5 and 0.8%, respectively) and T2a (23, 5 and 0.3%) groups than in the T2b group (29, 11 and 1.8%). The 5-year recurrence-free survival rate was 85% for T1c, 83% for T2a and 72% for T2b cases. Multivariate analysis indicated a decreased risk of recurrence for the T1c group compared to the T2a and T2b groups. The 5-year disease specific survival rate was 100% for the T1c and T2a groups, and 97% for the T2b group. CONCLUSIONS: Clinical and pathological features were similar for stages T1c and T2a, and different from stage T2b cancers. The 5-year recurrence-free survival was similar for T1c and T2a (log rank 0.89, p = 0.34), and higher than that for T2b (log rank 34.5, p <0.0001) cancers. However, controlling for all other prognostic factors on a Cox multivariate model, the risk of cancer recurrence was decreased for T1c compared to T2a and T2b disease. The detection of nonpalpable prostate cancer appears to be advantageous for intermediate-term cancer control.

Adult

Potency, continence and complication rates in 1,870 consecutive radical retropubic prostatectomies.

PURPOSE: We update results in a series of consecutive patients treated with anatomic radical retropubic prostatectomy regarding recovery of erections, urinary continence and postoperative complications. MATERIALS AND METHODS: One surgeon performed anatomic radical retropubic prostatectomy on 1,870 men, using the nerve sparing modification when feasible. We evaluated recovery of erections and urinary continence in men followed for a minimum of 18 months. Patients who were not reliably potent before surgery, did not undergo a nerve sparing procedure, or received hormonal therapy or postoperative adjuvant radiotherapy were excluded from the analysis of potency rates but not of continence rates. Other postoperative complications were evaluated for the entire patient population. RESULTS: Recovery of erections occurred in 68% of preoperatively potent men treated with bilateral (543 of 798) and 47% treated with unilateral (28 of 60) nerve sparing surgery. Recovery of erections was more likely with bilateral than with unilateral nerve sparing surgery in patients less than 70 years old (71 versus 48%, p<0.001) compared with patients with age 70 years old or older (48 versus 40%, p = 0.6). Recovery of urinary continence occurred in 92% (1,223 of 1,325 men) and was associated with younger age (p<0.0001) but not with tumor stage (p = 0.2) or nerve sparing surgery (p = 0.3). Postoperative complications occurred in 10% of patients overall and were associated with older age (p<0.002) but the incidence declined significantly with increasing experience of the surgeon (p<0.0001). There was no operative mortality. CONCLUSIONS: Anatomic radical retropubic prostatectomy with the nerve sparing modification can be performed with favorable results in preserving potency and urinary continence. Better results are achieved in young men with organ confined cancer. Other complications can be reduced with increasing surgeon experience.

Adult

Prediction of post-radical prostatectomy pathological outcome for stage T1c prostate cancer with percent free prostate specific antigen: a prospective multicenter clinical trial.

PURPOSE: Prostate specific antigen (PSA) exists in bound (complexed) and unbound (free) forms in serum. The percentage of free PSA enhances the specificity of PSA testing for prostate cancer detection. We evaluated the use of percent free PSA preoperatively to predict pathological stage. MATERIALS AND METHODS: A total of 379 men with prostate cancer and 394 with benign prostatic disease 50 to 75 years old were enrolled in this prospective study at 7 medical centers. All subjects had a palpably benign prostate gland, serum PSA 4.0 to 10.0 ng./ml. and a histologically confirmed diagnosis. The Hybritech Tandem PSA and free PSA assays were used. Of the 379 cancer patients 268 (71%) underwent radical prostatectomy. RESULTS: Higher percent free PSA levels were associated with more favorable histopathological findings in prostatectomy specimens. A value of 15% free PSA provided the greatest discrimination in predicting favorable pathological outcome. Organ confined cancer, Gleason sum less than 7 and small tumors (10% or less involvement of the prostate) were noted in 75% of patients with greater than 15% and only 34% with 15% or less free PSA (p<0.001). Multivariate logistic regression analysis revealed percent free PSA to be the strongest predictor of postoperative pathological outcome (odds ratio 2.25), followed by biopsy Gleason sum (2.06) and patient age (1.35). Total PSA was not predictive in this cohort but has been shown in prior studies to be predictive of outcome when a broader range of PSA values is evaluated. CONCLUSIONS: Percent free PSA may be used for risk assessment of the presence (diagnosis) and stage of prostate cancer in men with PSA between 4 and 10 ng./ml. Percent free PSA may be combined with PSA, digital rectal examination and biopsy findings to help predict postoperative pathological stage and grade, and may assist the patient and physician in making more informed treatment decisions.

Aged

Refined testing and targeted therapy lead new fight against prostate cancer. Interview by Wayne Kuznar.

Prostate cancer screening and intervention remain controversial, despite significant strides in the detection and treatment of this common malignancy. False-positive results from the test for prostate specific antigen (PSA) lead to unnecessary workups and biopsies, as well as psychological stress for patients. Radial prostatectomy remains the most effective treatment for organ-confined cancer, yet many patients opt for the opt for the organ-sparing advantage of radiation therapy. Others may opt for unproven interventions such as cryoablation. Recently-developed tools designed for use with PSA testing are helping to improve screening accuracy in the lower tier of serum total PSA (2.5 to 10.0 ng/mL).

Adult

The effect of high grade prostatic intraepithelial neoplasia on serum total and percentage of free prostate specific antigen levels.

PURPOSE: It is established that the percentage of free prostate specific antigen (PSA) in serum is low in patients with prostate cancer. An unanswered question is whether a low percentage of free PSA can be explained by high grade prostatic intraepithelial neoplasia alone. We compared the percentage of free PSA in men with high grade prostatic intraepithelial neoplasia alone, prostate cancer, benign prostatic hyperplasia (BPH) and a normal prostate (that is normal digital rectal examination and PSA less than or equal to 2.5 ng./ml.). MATERIALS AND METHODS: From October 1994 through December 1997, 48 men were diagnosed with high grade prostatic intraepithelial neoplasia without concomitant prostate cancer. Of these men 43 with a mean age plus or minus standard deviation of 67.4 +/- 7.8 years comprised our study group. To date none has been diagnosed with cancer during followup. Serum free and total PSA levels were measured, and the percentage of free PSA was calculated. The percentage of free PSA in the 43 men was compared to that in 50 with prostate cancer (mean age 65.4 +/- 7.8 years), 50 with biopsy proved BPH (67 +/- 7) and 43 with a normal prostate (61 +/- 8). RESULTS: There was no significant difference in mean total serum PSA in patients with high grade prostatic intraepithelial neoplasia, prostate cancer or BPH. The percentage of free PSA was significantly lower in patients with prostate cancer (14.9 +/- 6.5%) than those with high grade prostatic intraepithelial neoplasia (20.8 +/- 7.1%), BPH (20.1 +/- 7.3%) or a normal prostate (27.7 +/- 12.2%). There was also no significant difference in the percentage of free PSA between men with high grade prostatic intraepithelial neoplasia (20.8 +/- 7.1%) and those with BPH (20.1 +/- 7.3%). Additionally, men with a normal prostate had a higher percentage of free PSA (27.7%) than those with BPH (20.1%), high grade prostatic intraepithelial neoplasia (20.8%) or prostate cancer (14.9%). CONCLUSIONS: The percentages of free PSA in men with high grade prostatic intraepithelial neoplasia and BPH are similar, and significantly higher than those found in men with prostate cancer.

Aged

The combination of human glandular kallikrein and free prostate-specific antigen (PSA) enhances discrimination between prostate cancer and benign prostatic hyperplasia in patients with moderately increased total PSA.

BACKGROUND: Prostate-specific antigen (PSA) is the most reliable tumor marker available and is widely used for the diagnosis and management of prostate cancer. Unfortunately, PSA cannot distinguish efficiently between benign and malignant disease of the prostate, especially within the range of 4-10 microg/L. Among the refinements developed to enhance PSA specificity is the free/total PSA ratio, which is useful in discriminating between the two diseases within the diagnostic "gray zone". Recent data indicate that human glandular kallikrein (hK2), a protein with high homology to PSA, may be an additional serum marker for the diagnosis and monitoring of prostate cancer. METHODS: We analyzed 206 serum samples (all before treatment was initiated) from men with histologically confirmed benign prostatic hyperplasia (n = 100) or prostatic carcinoma (n = 106) with total PSA in the range of 2.5-10 microg/L. Total and free PSA and hK2 were measured with noncompetitive immunological procedures. Statistical analysis was performed to investigate the potential utility of the various markers or their combinations in discriminating between benign prostatic hyperplasia and prostatic carcinoma. RESULTS: hK2 concentrations were not statistically different between the two groups of patients. There was a strong positive correlation between hK2 and free PSA in the whole patient population. hK2/free PSA ratio (area under the curve = 0.69) was stronger predictor of prostate cancer than the free/total PSA ratio (area under the curve = 0.64). At 95% specificity, the hK2/free PSA ratio identified 30% of patients with total PSA between 2.5-10 microg/L who had cancer. At 95% specificity, the hK2/free PSA ratio identified 25% of patients with total PSA between 2.5 and 4.5 microg/L who had cancer. CONCLUSIONS: Our data suggest that hK2 in combination with free and total PSA can enhance the biochemical detection of prostate cancer in patients with moderately increased total PSA concentrations. More specifically, the hK2/free PSA ratio appears to be valuable in identifying a subset of patients with total PSA between 2.5 and 4.5 microg/L who have high probability of cancer and who should be considered for biopsy.

Aged