M K Brawer

Publications (92)628.14 Total impact

• Article: Perspectives on prostate cancer diagnosis and treatment: a roundtable.

  M K Brawer, T A Stamey, J Fowler, M Droller, E Messing, W R Fair
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  ABSTRACT: This roundtable was held September 30, 2000. It addressed, first of all, the accuracy and proper interpretation of the available prostate-specific antigen assays. Dr. Brawer presented data to demonstrate the specificity of the complexed prostate-specific antigen assay. Dr. Stamey counterpoised evidence that pretreatment prostate-specific antigen levels less than 9 ng/mL are attributable to benign prostatic hyperplasia and therefore are of little value as an indicator of when to initiate treatment for prostate cancer. The other roundtable participants offered reviews and new data regarding hormonal therapy as primary or adjunctive treatment of prostate cancer. Dr. Fowler presented a large retrospective series of men with locally advanced prostate cancer for whom androgen ablation was the primary therapy. Dr. Droller discussed his center's experience in integrating hormonal therapy with brachytherapy. Finally, Dr. Messing reviewed and critiqued the evidence that the combination of hormonal and radiation therapy improves survival.
  Urology 09/2001; 58(2):135-40. · 2.43 Impact Factor
• Article: Long-term stability of alpha-1-antichymotrypsin complexed form of prostate specific antigen.

  M K Brawer, L F Ferreri, D D Bankson
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  ABSTRACT: PSA complexed with alpha-1-anti-chymotrypsin (cPSA trade mark ) is the moiety in greatest proportion in the serum of men with prostate cancer (CAP). The performance of this analyte has been established primarily in retrospective archival serum. Studies indicate cPSA trade mark provides the specificity enhancement of the free-to-total PSA ratio, yet obviates the need to measure two markers. In the present investigation we sought to establish the stability of cPSA trade mark with long-term storage. Serum from men undergoing ultrasound-guided biopsy was utilized. Serum was assayed soon after collection and 18 months later. All serum was initially aliquotted and stored at -80 degrees C. There was no freeze-thaw. cPSA trade mark was measured utilizing the Bayer Immuno 1 method according to manufacturer's recommendations. The mean (s.d.) PSA was 5.5 (3.8) and 5.6 (3.9) ng/ml at the initial and subsequent testing, respectively. The medians were 4.3 and 4.4 ng/ml, respectively. No significant differences exist between the two determinants (r(2)=1.0, slope=1.01, t-test P=0.9194). These data establish for the first time the long-term stability of cPSA trade mark. Retrospective studies performed on archival material should give meaningful results. Prostate Cancer and Prostatic Diseases (2000) 3, 191-194
  Prostate cancer and prostatic diseases 12/2000; 3(3):191-194. · 2.10 Impact Factor
• Article: Comparison of percent free PSA, PSA density, and age-specific PSA cutoffs for prostate cancer detection and staging.

  W J Catalona, P C Southwick, K M Slawin, A W Partin, M K Brawer, R C Flanigan, A Patel, J P Richie, P C Walsh, P T Scardino, P H Lange, G H Gasior, K G Loveland, K R Bray
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  ABSTRACT: Various methods have been proposed to increase the specificity of prostate-specific antigen (PSA), including age-specific PSA reference ranges, PSA density (PSAD), and percent free PSA (%fPSA). In this multicenter study, we compared these methods for their utility in cancer detection and their ability to predict pathologic stage after radical prostatectomy in patients with clinically localized, Stage T1c cancer. Seven hundred seventy-three men (379 with prostate cancer, 394 with benign prostatic disease), 50 to 75 years old, from seven medical centers were enrolled in this prospective blinded study. All subjects had a palpably benign prostate, PSA 4.0 to 10.0 ng/mL, and a histologically confirmed diagnosis. Hybritech's Tandem PSA and free PSA assays were used. %fPSA and age-specific PSA cutoffs enhanced PSA specificity for cancer detection, but %fPSA maintained significantly higher sensitivities. Age-specific PSA cutoffs missed 20% to 60% of cancers in men older than 60 years of age. %fPSA and PSAD performed equally well for detection (95% sensitivity) if cutoffs of 25% fPSA or 0.078 PSAD were used. The commonly used PSAD cutoff of 0.15 detected only 59% of cancers. %fPSA and PSAD also produced similar results for prediction of the post-radical prostatectomy pathologic stage. Patients with cancer with higher %fPSA values (greater than 15%) or lower PSAD values (0.15 or less) tended to have less aggressive disease. The results of this study demonstrated that cancer detection (sensitivity) is significantly higher with %fPSA than with age-specific PSA reference ranges. %fPSA and PSAD provide comparable results, suggesting that %fPSA may be used in place of PSAD for biopsy decisions and in algorithms for prediction of less aggressive tumors since the determination of %fPSA does not require ultrasound.
  Urology 09/2000; 56(2):255-60. · 2.43 Impact Factor
• Article: Complexed prostate specific antigen provides significant enhancement of specificity compared with total prostate specific antigen for detecting prostate cancer.

  M K Brawer, C D Cheli, I E Neaman, J Goldblatt, C Smith, M K Schwartz, D J Bruzek, D L Morris, L J Sokoll, D W Chan, K K Yeung, A W Partin, W J Allard
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  ABSTRACT: Determining serum total prostate specific antigen (PSA) has proved to be a valuable diagnostic aid for detecting prostatic carcinoma, although the lack of specificity has limited its usefulness. Studies indicate that the use of percent free PSA would improve specificity while maintaining sensitivity. Since complexed PSA represents the major proportion of measurable PSA in serum, we determined whether it represents a single test alternative to the use of percent free PSA for the early detection of prostate cancer. Archival serum was obtained from 385 men with no evidence of malignancy on biopsy and 272 with biopsy confirmed prostate cancer. We determined the concentration and proportion of total, complexed and free PSA. Receiver operating characteristics analysis using total PSA results from all samples (range 0.32 to 117 ng./ml.) indicated that the areas under the curve for complexed PSA alone as well as the free-to-total and complexed-to-total PSA ratios were similar and significantly greater than those for total PSA alone. Within the range of 85% to 95% sensitivity receiver operating characteristics analysis revealed that the specificity of complexed PSA was higher than that of total PSA and equivalent to that of the free-to-total PSA ratio. We noted a similar improvement in specificity in the 4 to 10 ng./ml. total PSA range. Using published cutoff values for complexed, total and percent free PSA when total PSA was in the 4 to 10 ng./ml. range the sensitivity and specificity of complexed and percent free PSA were similar. Within the 4 to 10 ng./ml. total PSA range the population of patients with no evidence of malignancy and complexed PSA below the upper limit was different with respect to total PSA from that with no evidence of malignancy and free PSA greater than 25%. The measurement of complexed PSA represents an alternative to the use of percent free PSA, although the patient populations identified by the 2 tests are different.
  The Journal of Urology 06/2000; 163(5):1476-80. · 3.75 Impact Factor
• Article: Percentage of free PSA in black versus white men for detection and staging of prostate cancer: a prospective multicenter clinical trial.

  W J Catalona, A W Partin, K M Slawin, C K Naughton, M K Brawer, R C Flanigan, J P Richie, A Patel, P C Walsh, P T Scardino, P H Lange, J B deKernion, P C Southwick, K G Loveland, R E Parson, G H Gasior
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  ABSTRACT: 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. 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. 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. 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.
  Urology 03/2000; 55(3):372-6. · 2.43 Impact Factor
• Article: Report on Prostate Cancer Tumor Marker Workshop 1999.

  A W Partin, G P Murphy, M K Brawer
  Cancer 03/2000; 88(4):955-63. · 4.77 Impact Factor
• Article: Vasectomy and risk of prostate cancer.

  J L Stanford, K G Wicklund, B McKnight, J R Daling, M K Brawer
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  ABSTRACT: Most studies do not support an association between vasectomy and prostate cancer, but a few have suggested a link. Vasectomy is a common birth control method, and prostate cancer is the most frequently diagnosed solid tumor in men, making this a major public health question. This study was specifically designed to determine whether or not vasectomy is associated with risk of prostate cancer. To examine this issue, we conducted a population-based case-control study in King County, Washington. Interviews were completed with men ages 40-64 years newly diagnosed with prostate cancer between January 1993 and December 1996 who were ascertained through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) cancer registry (n = 753) and with comparison men without prostate cancer identified from the same general population (n = 703). The odds ratio (OR) for prostate cancer in relation to vasectomy was assessed. The prevalence of vasectomy was similar in cases (39.4%) and controls (37.7%), resulting in no association (adjusted OR, 1.10; 95% confidence interval, 0.9-1.4). There was no consistent evidence that risk varied by the age at which vasectomy was performed, the time since vasectomy, or the calendar period when the vasectomy was performed. The OR in relation to vasectomy was higher in men with less aggressive prostate cancer. Risk estimates did not differ according to age, race, or family history of prostate cancer. This study suggests that vasectomy is not associated with the risk of developing prostate cancer. It also provides evidence that vasectomized men may be more likely to present with earlier-stage, lower-grade prostate tumors.
  Cancer Epidemiology Biomarkers &amp Prevention 11/1999; 8(10):881-6. · 4.12 Impact Factor
• Article: Prediction of post-radical prostatectomy pathological outcome for stage T1c prostate cancer with percent free prostate specific antigen: a prospective multicenter clinical trial.

  P C Southwick, W J Catalona, A W Partin, K M Slawin, M K Brawer, R C Flanigan, A Patel, J P Richie, P C Walsh, P T Scardino, P H Lange, G H Gasior, R E Parson, K G Loveland
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  ABSTRACT: 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. 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. 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. 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.
  The Journal of Urology 11/1999; 162(4):1346-51. · 3.75 Impact Factor
• Article: Differences in prostate size between patients from University and Veterans Affairs Medical Center populations.

  R G Nixon, G E Meyer, M K Brawer
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  ABSTRACT: Numerous studies on prostatic disease have been performed at Veterans Affairs (VA) Medical Centers. Recent investigations evaluating early detection of prostate cancer provide insight that the average prostate volume may be different between patients with similar clinical findings who are from different hospital settings. The objective of this study was to compare prostate size between men from University and VA Medical Centers. Patients were enrolled retrospectively from 1989-1996 from the Urology Clinics at a University and a VA Medical Center. All men underwent transrectal ultrasound-guided sextant biopsy of the prostate owing to either an elevated prostate-specific antigen (PSA) level and/or abnormal digital rectal examination (DRE) detected prior to biopsy. Prostate volume was calculated using the ellipsoid three-diameter formula based on transrectal ultrasound measurements. There were 1,311 men included in the analysis: 717 were from the VA, and 594 were from the University. The average prostate volume was significantly smaller among VA patients both for men with cancer (P = 0.0004) and for men with no evidence of malignancy (P < 0.0001). Overall, the average prostate volume was 38.5 cm3 (median, 32.5 cm3) among men from the VA compared to 46.8 cm3 (median, 39.3 cm3) among men from the University Medical Center. Men from the VA were older (mean +/- SD = 68 +/- 7.3) than men from the University (mean +/- SD = 66 +/- 7.7) (P = 0.004) and there was no significant difference in PSA levels between the two groups of patients (P = 0.11). Intriguingly, the incidence of cancer was significantly lower at the VA (24.5%) compared to the University (35.9%) (P < 0.0001). The variance in prostate size suggests that there are significant differences between the two patient populations. Proposed factors leading to this discrepancy include differences in socioeconomic factors, environmental factors, and changes in hormonal milieu related to alcohol and tobacco use. These results may have significant implications regarding the interpretation and extrapolation of results from previous studies performed at a single hospital setting.
  The Prostate 03/1999; 38(2):144-50. · 3.48 Impact Factor
• Article: Prostate cancer in relation to the use of electric blanket or heated water bed.

  K Zhu, N S Weiss, J L Stanford, J R Daling, A Stergachis, B McKnight, M K Brawer, R S Levine
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  ABSTRACT: Using data from a case-control study conducted in Group Health Cooperative (GHC) of Puget Sound, we examined the relation between the use of electric blankets or heated water beds and the risk of prostate cancer. Cases were 175 prostate cancer patients ages 40-69 years. Controls were 258 male GHC members frequency matched to cases. The odds ratio (OR) for prostate cancer associated with the use of an electric blanket or heated water bed was 1.4 (95% confidence interval (CI) 0.9-2.2). The risk, however, did not tend to be higher with increasing months per year or years of use. This study did not provide clear evidence on the hypothesized association.
  Epidemiology 02/1999; 10(1):83-5. · 5.57 Impact Factor
• Article: Prostate cancer: epidemiology and screening.

  M K Brawer
  Prostate cancer and prostatic diseases 02/1999; 2(S1):2-6. · 2.10 Impact Factor
• Article: The effect of prostate volume on the yield of needle biopsy.

  J L Letran, G E Meyer, F R Loberiza, M K Brawer
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  ABSTRACT: Early diagnosis of prostate carcinoma has undergone significant evolution mainly due to the widespread use of serum prostate specific antigen, transrectal ultrasonography and spring loaded biopsy devices. A common dilemma faced by clinicians arises when a negative biopsy is obtained in a patient and there is a high suspicion for prostate carcinoma. The literature reveals a 20 to 40% positive repeat biopsy rate in men with elevated prostate specific antigen who had an initial negative biopsy. We determined the yield of 6 systematic sector biopsies as a function of total gland and peripheral zone volumes. The database of transrectal ultrasound guided prostate needle biopsies performed at the Department of Urology, University of Washington Medical Center and Veterans Affairs Puget Sound Health Care System was reviewed. The yield of the 6 biopsies was determined as a function of the total gland and peripheral zone volumes. A total of 1,057 men who underwent transrectal ultrasound guided prostate needle biopsies were investigated in our study. Of the men 326 were diagnosed with prostate cancer for a positive biopsy rate of 30.8%. No relationship between gland size and cancer yield was seen using total gland volume compared to the first quartile until the largest quartile when a significantly lower cancer detection rate was noted (odds ratio 1.5). The positive yield of the systematic 6-sector biopsy decreases significantly when the total gland volume is greater than 55.6 cc or peripheral zone volume is greater than 33.61 cc. In men with smaller prostates 6 systematic sector biopsies should be adequate.
  The Journal of Urology 12/1998; 160(5):1718-21. · 3.75 Impact Factor
• Article: Measurement of complexed PSA improves specificity for early detection of prostate cancer.

  M K Brawer, G E Meyer, J L Letran, D D Bankson, D L Morris, K K Yeung, W J Allard
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  ABSTRACT: Prostate-specific antigen (PSA) is the most useful of all tumor markers. Although the sensitivity is impressive, low specificity results in a lack of cancer detection in a significant proportion of patients undergoing prostate biopsy. Several recent studies have addressed the need for improved specificity. Of all these approaches, the free/total PSA ratio appears to be the most promising. Given that most circulating PSA is complexed to alpha1-antichymotrypsin, and that this moiety represents a greater proportion of the total PSA in those men with carcinoma, we set out to determine whether complexed PSA would improve specificity in the detection of men with prostate cancer. Archival sera were obtained from 300 men, 75 of whom had biopsy-proved prostate cancer. All sera had been previously stored at -70 degrees C for variable periods. An investigative assay for complexed PSA (Bayer) was used. The Tandem-R free and total PSA assays (Hybritech) were used according to the manufacturer's recommendations. Among all patients, specificities for the total PSA, free/total PSA, and complexed PSA alone were 21.8%, 15.6%, and 26.7%, respectively, at cutoffs yielding 95% sensitivity. Similar equivalence or superior performance, in terms of specificity relative to the free/total PSA ratio, was seen at other sensitivity thresholds and other total PSA ranges. Complexed PSA alone performs better than total PSA or the free/total PSA ratio and obviates the need for a second analyte determination. We believe this marker may offer significant enhancement in PSA testing with significant economic advantages.
  Urology 10/1998; 52(3):372-8. · 2.43 Impact Factor
• Article: Repeat ultrasound guided prostate needle biopsy: use of free-to-total prostate specific antigen ratio in predicting prostatic carcinoma.

  J L Letran, A B Blase, F R Loberiza, G E Meyer, S D Ransom, M K Brawer
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  ABSTRACT: Despite being the most useful tumor marker for the diagnosis of patients with prostate cancer, serum prostate specific antigen (PSA) is still hampered by lack of specificity. A negative prostate biopsy is associated with a 20 to 40% incidence of positive repeat biopsy in men with persistently elevated serum PSA levels. We determine whether the free-to-total PSA ratio could be predictive of prostate cancer in men undergoing repeat biopsy. Archival sera, drawn before the first biopsy, were gathered from 51 men with a total serum PSA of 2 to 15 ng./ml. who underwent repeat prostate needle biopsy for various indications. The percent free PSA was calculated using the Hybritech Tandem-Rt free and total PSA as well as Dianon Systems freet and Hybritech total PSA assays. The free-to-total PSA ratio results between the cancer and noncancer groups were compared using Student's t test. The median Hybritech free-to-total PSA ratio was significantly lower in patients with positive repeat prostate needle biopsy compared to those with negative biopsy (14.9 versus 19.4%, p=0.05). Total PSA as well as the percent Dianon free-to-Hybritech total PSA ratio were not significantly different between the 2 groups of men. For total PSA in the range of 2 to 15 ng./ml. Hybritech free-to-total PSA ratio appeared to aid in the prediction of cancer on repeat biopsy.
  The Journal of Urology 09/1998; 160(2):426-9. · 3.75 Impact Factor
• Article: Comparison of 3 investigational assays for the free form of prostate specific antigen.

  R G Nixon, G E Meyer, A B Blase, M H Gold, M K Brawer
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  ABSTRACT: Measuring percent free/total prostate specific antigen (PSA) versus total PSA alone has been shown to enhance the stratification of cases with and without prostate cancer. We compared the diagnostic performance of 3 free PSA assays when values were interchanged over a common total PSA denominator. Archival sera from 123 consecutively accrued patients (25 with prostate cancer, 98 with no evidence of malignancy) who had pre-biopsy total PSA levels from 2.0 to 20.0 ng./ml. were obtained from our specimen bank. Serum specimens were analyzed using the Hybritech Tandem R, Dianon Systems and Chiron ACS 180 free PSA assays. Total PSA was measured using the Hybritech Tandem R total PSA assay. Linear regression was performed to evaluate the correlation and agreement among assays. Sensitivity and specificity of cancer detection were calculated to compare diagnostic performance. The required percent free PSA cutoffs were different among the 3 free PSA assays. The cutoffs to ensure a 95% sensitivity of cancer detection were 22, 34 and 34%, and the number of negative biopsies that were prevented at these cutoffs (specificity) was 38, 19 and 33% for the Hybritech, Dianon, and Chiron assays, respectively. The results among the different assays were not interchangeable. Clinicians should be aware that different percent free PSA cutoffs need to be used based on the type of free and total PSA assays, and that not all assays diagnostically perform the same.
  The Journal of Urology 09/1998; 160(2):420-5. · 3.75 Impact Factor
• Article: Transition zone prostate specific antigen density: lack of use in prediction of prostatic carcinoma.

  D W Lin, M H Gold, S Ransom, W J Ellis, M K Brawer
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  ABSTRACT: Among the new approaches to enhance the performance of prostate specific antigen (PSA) testing in a biopsy population is the use of the free-to-total PSA as well as the transition zone density, which is calculated by dividing the PSA by the transition zone volume. We compare these manipulations of the PSA to PSA alone in a biopsy population. We evaluated 917 consecutive men who underwent ultrasound guided biopsy for an elevation in serum PSA or abnormality on digital rectal examination. Total PSA was measured using the Tandem-E or Tandem-R method. Prostate gland volume and transition zone were measured with ultrasound and calculated using the prolate ellipsoid formula. In the overall PSA range 276 men had carcinoma (30.0% of the population), while in the PSA 4.0 to 10.0 ng./ml. range 141 of 477 had cancer (29.6%). Receiver operating characteristics analysis and analysis of variance were performed. In the overall PSA series the Tandem total PSA performed as well as any PSA index to predict carcinoma. In the restricted range of total PSA 4.0 to 10.0 ng./ml. total PSA density as well as transition zone density were more predictive than PSA alone. In both PSA ranges the volume of benign glands was significantly larger than in the prostates exhibiting carcinoma. There was no statistically significant difference in outcomes of analyses between different investigators or different sites of investigation (Veterans Affairs versus university based hospitals). In this biopsy population transition zone PSA density did not add to the information available with total PSA and gland volume. Neither investigator nor site bias contributed to the failure of transition zone PSA density or PSA density to predict prostatic carcinoma.
  The Journal of Urology 08/1998; 160(1):77-81; discussion 81-2. · 3.75 Impact Factor
• Article: Prospective evaluation of percent free-PSA and complexed-PSA for early detection of prostate cancer.

  A W Partin, M K Brawer, E N P Subong, C A Kelley, J L Cox, D J Bruzek, J Pannek, G E Meyer, D W Chan
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  ABSTRACT: Aims of the study: Retrospective studies investigating the use of percent free-PSA for early detection of prostate cancer were limited for various reasons: by their use of long-term stored sera, poor mix of non-cancer to cancer cases and the use of only men with PSA values between 4.0 and 10.0 ng/mL. This prospective study investigates the clinical utility of percent free-PSA and complexed-PSA for early detection of prostate cancer in 219 consecutive men presenting for prostate biopsy. Methods: Of 246 consecutive men who underwent ultrasound guided sextant biopsy of the prostate for PSA elevation and/or suspicious digital rectal exam, 219 men had serum total PSA levels between 2.0 and 20.0 ng/mL and were included in this study. Serum total, free and complexed (PSA-ACT) were measured (Hybritech Inc.). Results: Pathologic examinations demonstrated that 72% and 28% of the biopsies were non-cancer and cancer respectively. The mean percent free-PSA was statistically different between the groups (cancer 14%+/-6.4 and non-cancer 18+/-9%, P<0.001) and improved cancer detection. PSA-ACT provided only modest improvement in cancer detection over that of total PSA. Among this cohort of men, the optimal total PSA reflex range for percent free-PSA was 3.0-7.0 ng/mL (38% specificity) with a percent free-PSA cut-off of 20% (95% sensitivity) yet only affected 56% of the cases. Conclusions: PSA-ACT added very little additional value to the clinical utility of total PSA for early detection. Percent free-PSA performed well for all reflex ranges. A sensitivity and specificity of 95% and 20% respectively were obtained using a single cut-off of 25% for percent free-PSA for the group of men with total PSA values between 4.0 and 10.0 and correlated well with recently reported prospective analyses.
  Prostate cancer and prostatic diseases 07/1998; 1(4):197-203. · 2.10 Impact Factor
• Article: Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial.

  W J Catalona, A W Partin, K M Slawin, M K Brawer, R C Flanigan, A Patel, J P Richie, J B deKernion, P C Walsh, P T Scardino, P H Lange, E N Subong, R E Parson, G H Gasior, K G Loveland, P C Southwick
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  ABSTRACT: The percentage of free prostate-specific antigen (PSA) in serum has been shown to enhance the specificity of PSA testing for prostate cancer detection, but earlier studies provided only preliminary cutoffs for clinical use. To develop risk assessment guidelines and a cutoff value for defining abnormal percentage of free PSA in a population of men to whom the test would be applied. Prospective blinded study using the Tandem PSA and free PSA assays (Hybritech Inc, San Diego, Calif). Seven nationwide university medical centers. A total of 773 men (379 with prostate cancer, 394 with benign prostatic disease) 50 to 75 years of age with a palpably benign prostate gland, PSA level of 4.0 to 10.0 ng/mL, and histologically confirmed diagnosis. A percentage of free PSA cutoff that maintained 95% sensitivity for prostate cancer detection, and probability of cancer for individual patients. The percentage of free PSA may be used in 2 ways: as a single cut-off (ie, perform a biopsy for all patients at or below a cutoff of 25% free PSA) or as an individual patient risk assessment (ie, base biopsy decisions on each patient's risk of cancer). The 25% free PSA cutoff detected 95% of cancers while avoiding 20% of unnecessary biopsies. The cancers associated with greater than 25% free PSA were more prevalent in older patients, and generally were less threatening in terms of tumor grade and volume. For individual patients, a lower percentage of free PSA was associated with a higher risk of cancer (range, 8%-56%). In the multivariate model used, the percentage of free PSA was an independent predictor of prostate cancer (odds ratio [OR], 3.2; 95% confidence interval [CI], 2.5-4.1; P < .001) and contributed significantly more than age (OR, 1.2; 95% CI, 0.92-1.55) or total PSA level (OR, 1.0; 95% CI, 0.92-1.11) in this cohort of subjects with total PSA values between 4.0 and 10.0 ng/mL. Use of the percentage of free PSA can reduce unnecessary biopsies in patients undergoing evaluation for prostate cancer, with a minimal loss in sensitivity in detecting cancer. A cutoff of 25% or less free PSA is recommended for patients with PSA values between 4.0 and 10.0 ng/mL and a palpably benign gland, regardless of patient age or prostate size. To our knowledge, this study is the largest series to date evaluating the percentage of free PSA in a population representative of patients in whom the test would be used in clinical practice.
  JAMA The Journal of the American Medical Association 06/1998; 279(19):1542-7. · 30.03 Impact Factor
• Article: Management of radiation failure for localized prostate cancer.

  J L Letran, M K Brawer
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  ABSTRACT: Due to the historically large number of patients with localized prostate cancer (CAP) treated by radiation therapy, an increasing number of patients are presenting local failure. The currently available concepts regarding its definition as well as management options are reviewed. The literature regarding radiation failure for localized prostate cancer was reviewed. Emphasis was made on articles concerning definition of radiation failure, patient evaluation and restaging and definitive as well as palliative management options. There is definitely a subset of patients with locally recurrent prostate cancer without evidence of metastasis that could potentially benefit from aggressive local therapy. A treatment algorithm is proposed but it should be emphasized that treatment options should be individualized to suit the need of a particular patient.
  Prostate cancer and prostatic diseases 04/1998; 1(3):119-127. · 2.10 Impact Factor
• Article: Interpretation of free prostate specific antigen clinical research studies for the detection of prostate cancer.

  D L Woodrum, M K Brawer, A W Partin, W J Catalona, P C Southwick
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  ABSTRACT: We reviewed the use of percent free prostate specific antigen (PSA) to enhance specificity of PSA testing and aid in the discrimination of benign and malignant prostate disease. We present proposed percent free PSA cut points and probability factors, and discuss factors that are believed to affect study outcomes and conclusions. We reviewed the literature with respect to PSA and free PSA with particular emphasis on clinical use of percent free PSA and factors that may affect study outcomes. Percent free PSA may increase the specificity of PSA testing without sacrificing the cancer detection rate. Differences in study designs and subject populations may account for the confusion in the current literature. Specific factors that may influence study outcomes include sample size, PSA range, age, race, digital rectal examination findings, prostate size, tumor size and pathology, as well as treatment history, sample collection and storage conditions, and the particular assays used to determine free and total PSA values. The use of percent free PSA to enhance the specificity of prostate cancer screening is thought to provide useful information to aid in the differentiation of benign and malignant prostate diseases. There is evidence to suggest a benefit cost advantage to a tailored biopsy approach based on percent free PSA. However, statistically valid multisite clinical trials that take into account influencing factors are needed to set assay specific cut points and probability determinations.
  The Journal of Urology 02/1998; 159(1):5-12. · 3.75 Impact Factor