Prebiopsy Prostate-specific Antigen Research Articles

Analysis of the Clinicopathologic Characteristics of Men with Prostate Cancer Undergoing Radical Prostatectomy in the Prostate-Specific Antigen Range of Less than 4 ng/ml

Purpose: We analyzed the clinicopathologic characteristics of men undergoing radical prostatectomy in the prostate-specific antigen (PSA) range of less than 4 ng/ml and compared this with the results for men who had a PSA range of 4 to 9.9 ng/ml. Materials and Methods: The study population consisted of 447 men treated for prostate cancer with radical prostatectomy between 1990 and 2006 at our institute who had a prebiopsy PSA of less than 10 ng/ml. The average follow-up period was 37 months. Clinicopathologic characteristics were compared between men with a PSA value of less than 4 ng/ml (low-PSA group) and men with a value in the range of 4 to 9.9 ng/ml (intermediatePSA group). Survival analysis was performed by the Kaplan-Meier method and Cox proportional hazard regression analysis. Results: Of these 447 patients, 60 (13.4%) and 387 (86.6%) had a low or an intermediate prebiopsy PSA level, respectively. The pathologic findings of the prostatectomy specimens showed no significant differences between the 2 groups, including Gleason score and pathologic stage. The 5-year biochemical recurrence-free survival in the lowand intermediate-PSA groups was 82.8% and 79.3%, respectively, and there was no significant difference between the 2 groups (p=0.946). Multivariate analysis showed that, in the entire cohort, pathologic Gleason score and lymph node involvement were independent predictors of biochemical recurrence. Conclusions: No statistically significant differences were found in clinicopathologic characteristics or clinical outcome between the lowand intermediate-PSA groups. These results suggest that a lower PSA cutoff should be considered as an indication for prostate biopsy in the Korean population. (Korean J Urol 2009;50:320-326) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Agent Orange exposure, Vietnam War veterans, and the risk of prostate cancer

It has been demonstrated that Agent Orange exposure increases the risk of developing several soft tissue malignancies. Federally funded studies, now nearly a decade old, indicated that there was only a weak association between exposure and the subsequent development of prostate cancer. Because Vietnam War veterans are now entering their 60s, the authors reexamined this association by measuring the relative risk of prostate cancer among a cohort of men who were stratified as either exposed or unexposed to Agent Orange between the years 1962 and 1971 and who were followed during the interval between 1998 and 2006. All Vietnam War era veterans who receive their care in the Northern California Veteran Affairs Health System were stratified as either exposed (n=6214) or unexposed (n=6930) to Agent Orange. Strata-specific incidence rates of prostate cancer (International Classification of Diseases, 9th Revision code 185.0) were calculated. Differences in patient and disease characteristics (age, race, smoking history, family history, body mass index, finasteride exposure, prebiopsy prostate-specific antigen (PSA) level, clinical and pathologic stage, and Gleason score) were assessed with chi-square tests, t tests, a Cox proportional hazards model, and multivariate logistic regression. Twice as many exposed men were identified with prostate cancer (239 vs 124 unexposed men, respectively; odds ratio [OR], 2.19; 95% confidence interval [95% CI], 1.75-2.75). This increased risk also was observed in a Cox proportional hazards model from the time of exposure to diagnosis (hazards ratio [HR], 2.87; 95% CI, 2.31-3.57). The mean time from exposure to diagnosis was 407 months. Agent Orange-exposed men were diagnosed at a younger age (59.7 years; 95% CI, 58.9-60.5 years) compared with unexposed men (62.2 years; 95% CI, 60.8-63.6 years), had a 2-fold increase in the proportion of Gleason scores 8 through 10 (21.8%; 95% CI, 16.5%-27%) compared with unexposed men (10.5%; 95% CI, 5%-15.9%), and were more likely to have metastatic disease at presentation than men who were not exposed (13.4%; 95% CI, 9%-17.7%) than unexposed men (4%; 95% CI, 0.5%-7.5%). In univariate analysis, distribution by race, smoking history, body mass index, finasteride exposure, clinical stage, and mean prebiopsy PSA were not statistically different. In a multivariate logistic regression model, Agent Orange was the most important predictor not only of developing prostate cancer but also of high-grade and metastatic disease on presentation. Individuals who were exposed to Agent Orange had an increased incidence of prostate cancer; developed the disease at a younger age, and had a more aggressive variant than their unexposed counterparts. Consideration should be made to classify this group of individuals as 'high risk,' just like men of African-American heritage and men with a family history of prostate cancer.

Pre-biopsy Prostate-specific Antigen Velocity does not Predict Gleason Score, Tumor Location or Cancer Volume Following Transperineal-template Guided Prostate Mapping Biopsy: Implications for Prostate Brachytherapy Treatment Planning

Pre-biopsy Prostate-specific Antigen Velocity does not Predict Gleason Score, Tumor Location or Cancer Volume Following Transperineal-template Guided Prostate Mapping Biopsy: Implications for Prostate Brachytherapy Treatment Planning

Pre-biopsy prostate-specific antigen velocity does not predict Gleason score, tumor location or cancer volume following transperineal template-guided prostate mapping biopsy

Pre-biopsy prostate-specific antigen velocity does not predict Gleason score, tumor location or cancer volume following transperineal template-guided prostate mapping biopsy

DISCREPANCIES IN GLEASON SCORING OF PROSTATE BIOPSIES AND RADICAL PROSTATECTOMY SPECIMENS AND THE EFFECTS OF MULTIPLE NEEDLE BIOPSIES ON SCORING ACCURACY. A REGIONAL EXPERIENCE IN TAMWORTH, AUSTRALIA

The aim of this study was to review the discrepancies in Gleason scores (GS) of prostate biopsies and radical prostatectomy specimens and the effects of multiple-needle biopsies on scoring accuracy. One hundred patients who had undergone consecutive radical prostatectomies (RP) between January 2004 and May 2006 were reviewed retrospectively. Patient information including age, prebiopsy prostate-specific antigen levels, biopsy GS, RP GS and pathology details were recorded and compared. The concordance rate of biopsy GS and RP GS was found to be at 43%, with 46% of biopsy specimens being undergraded. Eleven per cent of the specimens were overgraded. The accuracy was fairly similar when specimens were reported by the same or different pathologists, at 42 and 44%, respectively. The accuracy of biopsy GS improved with increasing number of biopsies taken. There are significant discrepancies in Gleason scoring of biopsy and RP specimens, with a concordance rate of 43% and undergrading rate of 46%. Increasing the number of biopsies helps improve scoring accuracy. Clinicians and patients need to be mindful when deciding cancer treatment options, in view of these discrepancies.

Assessment of Prostate-Specific Antigen Doubling Time in Prediction of Prostate Cancer on Needle Biopsy

Prostate-specific antigen (PSA) kinetics have failed to predict for the presence of prostate cancer in screening populations in which many patients harbor subclinical disease. We hypothesized that the prebiopsy PSA doubling time (PSADT) and PSA velocity (PSAV) could predict for cancer detection in a referral population with a suspicion of prostate cancer. Data were collected from 1699 consecutive veterans with a PSA level of 10 ng/mL or less who underwent prostate biopsy. Logistic regression analysis was performed on the following: age, race, family history, digital rectal examination findings, PSA, PSA density, PSADT, PSAV, prostate volume, and ultrasound lesions. Model building was accomplished with 70% of the data, and validation was done using the remaining 30%. These data were also analyzed using classification and regression tree analysis. Using logistic regression analysis (P <0.05) on the model building set, prostate cancer was associated with age (older than 70 years), PSA level (greater than 2.9 ng/mL), PSA density (more than 0.12 ng/mL/cm3), digital rectal examination findings, and the presence of a lesion on ultrasonography. A PSADT of 2 to 5 years was marginally associated with prostate cancer detection (odds ratio 1.6, 95% confidence interval 1.1 to 2.3), and a PSADT of less than 2 years or longer than 5 years and PSAV were not predictive. On classification and regression tree analysis, PSADT was not selected as a predictive factor. Furthermore, neither PSADT nor PSAV was predictive of Gleason score 7 or worse cancer. In contrast to its prognostic value after the diagnosis of prostate cancer has been established, PSA kinetics offer little to clinical decision making as predictors of cancer or high-grade cancer in men with a PSA level of 10 ng/mL or less.

Pathological Outcomes and Biochemical Progression in Men With T1c Prostate Cancer Undergoing Radical Prostatectomy With Prostate Specific Antigen 2.6 to 4.0 vs 4.1 to 6.0 ng/ml

Recent studies have suggested that the cut point for recommending prostate biopsy among men with a normal digital rectal examination should be greater than 2.5 ng/ml as opposed to the more traditional greater than 4.0 ng/ml. We compared outcomes between men with clinical stage T1c disease undergoing radical prostatectomy who had a low vs slightly increased prostate specific antigen. The study population consisted of 2,896 men treated with radical prostatectomy between 1985 and 2004 at a tertiary care referral center with clinical stage T1c disease and a pre-biopsy prostate specific antigen between 2.6 and 6.0 ng/ml. Using multivariate analysis we evaluated the association between pre-biopsy prostate specific antigen 2.6 to 4.0 ng/ml (784) vs 4.1 to 6.0 ng/ml (2,112), and pathological outcomes and biochemical progression. After adjusting for multiple clinical and pathological characteristics, lower preoperative serum prostate specific antigen values were associated with decreased odds of Gleason score 7 or greater in the surgical specimen (p = 0.004), positive surgical margins (p = 0.02) and extraprostatic extension (p = 0.001). There was no significant association between these preoperative prostate specific antigen groups and odds of seminal vesicle invasion (p = 0.47) or lymph node metastasis (p = 0.90). Among the 1,534 men with followup information available there was a trend for increased risk of biochemical progression associated with a higher preoperative prostate specific antigen, although this trend did not reach statistical significance (relative risk 1.48, 95% CI 0.69-3.19, p = 0.31). In the current study of men with clinical stage T1c treated with radical prostatectomy a lower preoperative prostate specific antigen was associated with significantly more favorable pathological findings. Whether this degree of improved outcomes justifies the limitations associated with decreasing the prostate specific antigen cut point (eg increased biopsies performed and diagnosis of insignificant cancers) remains to be determined.

Pre-biopsy PSA and biopsy gleason sum; evaluating the independence of two independent variables

14555 Background: Traditionally PSA, Gleason sum and Clinical Stage are considered independent predictors of outcome for prostate cancer. The purpose of this study is to investigate a codependence between prostate specific antigen (PSA) and Gleason sum and whether this relationship has evolved during the PSA era. Methods: The Columbia Urologic Oncology Database was reviewed and 2,522 patients were identified who underwent radical prostatectomy from 1988 to 2005; a retrospective cohort of 1,786 patients with complete data was included. Patients were stratified by Gleason sum into groups with Gleason sum &lt;7, =7 and &gt;7. PSA was correlated to Gleason sum to examine a possible relationship between the two variables. Two-sample t-tests with 95% confidence intervals were utilized to determine differences between groups and were confirmed by ANOVA techniques. A Cox regression model using an interaction term between PSA and Gleason sum was fit to determine if an interaction exists between the two variables. Patients were further stratified into two cohorts by median year of surgery (1998) and the PSA-Gleason sum relationship was evaluated over time. Results: Median patient age was 61.9 years. 1,081 patients were identified with Gleason sum &lt;7. 540 patients had a Gleason sum =7. 165 patients had a Gleason sum &gt;7. The mean PSA values were 6.05, 6.89 and 8.41 for &lt;7, =7 and &gt;7 groups respectively. Differences between the means were statistically significant and validated by the ANOVA technique (p &lt; 0.001). A Cox regression model validated PSA, Gleason sum and clinical stage as independent predictors of outcome. The addition of an interaction term into the Cox regression model between PSA and Gleason sum demonstrated a significant interaction effect between PSA and Gleason sum (p &lt; 0.001). The relationship remained between PSA and Gleason sum within the pre and post 1998 groups (p &lt; 0.001). Conclusions: PSA and Gleason sum are highly interrelated variables, although they each carry additional information that significantly contributes to the prediction of biochemical failure (PSA ≥0.2 ng/ml). For an individual patient, the higher the initial PSA the higher the risk of having a high Gleason sum on biopsy. This relationship has remained constant over the PSA era. No significant financial relationships to disclose.

A Study on Staging Bone Scans in Newly Diagnosed Prostate Cancer

Objective: This study aimed to evaluate the role of bone scan as a staging investigation in newly diagnosed untreated prostate cancers. Materials and Methods: Bone scan results in patients with newly diagnosed prostate cancer were reviewed and correlated with clinical stage, prostate-specific antigen (PSA) and Gleason scores from the biopsy specimen. Results: In all, 124 patients fulfilled inclusion criteria with an age range of 51–94 (mean 72.3) years. Pre-biopsy PSA ranged from 2.2 to 5,864 with a median of 21.1 ng/ml. Clinical stage was T0-T1c 14.5%, T2a 41.9%, T2b 17.7%, T3 16.9%, and T4 9%. A Gleason score of 7 was found in 31%. Four patients’ samples were not suitable for Gleason scoring. Twenty patients (16.1%) had a positive bone scan with a mean age of 79.4 years (median 83). Two patients with PSA <20 ng/ml were positive. Of the 44 scans performed in the patients with PSA ≤20 ng/ml, clinical stage <T4 and Gleason sum ≤7 (with the major Gleason <4), none was positive. The above criteria give a 100% negative predictive value for avoiding bone scans as a staging investigation. Conclusions: Staging bone scan can be safely omitted in patients with a clinical stage of <T4, PSA level of ≤20 ng/ml and a Gleason score of ≤7 (with major Gleason pattern <4) unless the symptoms are suggestive of metastasis.

Interval from prostate biopsy to radical prostatectomy: Effect on PSA, Gleason sum, and risk of recurrence

Objectives To determine whether the change in prostate-specific antigen (PSA), change in Gleason sum, and/or interval between prostate biopsy and radical prostatectomy have an association with biochemical recurrence. Methods The relationship between biochemical recurrence and the interval between biopsy and surgery, as well as the rate and amount of change in PSA and Gleason sum from biopsy to surgery, was evaluated in 151 patients with prostate cancer treated with radical prostatectomy. Results A statistically significant increase was found in PSA level and Gleason sum between biopsy and surgery ( P = 0.01 and P <0.0001, respectively). No significant association was found between prebiopsy PSA level ( P = 0.27) or biopsy Gleason sum ( P = 0.07) with biochemical recurrence as independent variables or in a combined model ( P = 0.12). An association was also not found between recurrence and preprostatectomy PSA level ( P = 0.15) or the rate of PSA change ( P = 0.28) as independent variables. However, a significant association was found with the prostatectomy Gleason sum ( P = 0.001). In a combined model, a significant association was noted between the preprostatectomy PSA level and prostatectomy specimen Gleason sum and biochemical recurrence ( P = 0.003). No increased risk of biochemical recurrence was noted with increasing time from biopsy to prostatectomy (odds ratio 1.00) or the rate (odds ratio 1.03) and degree (odds ratio 1.30) of serum PSA or Gleason sum (odds ratio 1.07). Conclusions The interval between biopsy and radical prostatectomy is not a predictor of biochemical failure. An association was noted between an increased risk of biochemical failure and the amount of serum PSA and Gleason sum increase between biopsy and surgery.

USE OF EXTENDED PATTERN TECHNIQUE FOR INITIAL PROSTATE BIOPSY

An extended prostate biopsy schema has been advocated at initial prostate biopsy to decrease the rate of false-negative cancer cases. However, critics have raised concerns that this may lead to the greater detection of clinically insignificant cancers. We examined the impact of using an extended pattern schema on cancer detection and also on the finding of smaller and clinically insignificant cancer. Clinical data, including patient age, race, prebiopsy prostate specific antigen (PSA), digital rectal examination, prostate volume, number of needle cores and biopsy findings were abstracted from the medical records of all patients who underwent prostate biopsy in a 5-year period. Extended pattern prostate biopsy was defined as more than 10 cores. Clinically insignificant cancer was defined as a maximal tumor dimension of 1.0 cm or less, Gleason sum 6 or less and organ confined disease at radical prostatectomy. Adjusted regression models were developed to assess the independent effects of using an extended biopsy pattern on the detection of cancer overall and on the detection of clinically insignificant cancer. A total of 740 men with a mean age of 62.6 years were referred for prostate biopsy. Median PSA was 5.7 ng/ml and prostate volume was 39.7 cc. The OR for detecting prostate cancer was 1.55 (95% CI 1.09 to 2.19) for the extended pattern compared with standard biopsy. Of the subset of 136 patients who underwent radical prostatectomy 12.6% had clinically insignificant cancer. However, in contrast to overall cancer detection, extended pattern prostate biopsy was not found to be associated with an increased risk of detecting smaller or clinically insignificant cancer. PSA density was the single parameter found to be independently associated with the detection of clinically insignificant cancer (95% CI 0.20 to 0.98). Using an extended prostate biopsy pattern involving more than 10 cores increases the likelihood of detecting prostate cancer. A significant association between more needle cores at initial prostate biopsy and finding smaller and clinically insignificant cancer was not apparent.

Prediction of Response to Salvage Radiation Therapy in Patients With Prostate Cancer Recurrence After Radical Prostatectomy

To identify factors predictive of local recurrence as defined by a complete response to salvage radiation therapy in patients whose disease recurs after radical prostatectomy. Ninety-five patients with recurrence after radical prostatectomy who were evaluated by prostatic fossa biopsies, and a subset of 49 of these patients treated with radiation for control of presumed or biopsy-proven local recurrence, were studied. Biopsies were positive in 40 (42%) of the 95 biopsied patients. Multivariate analysis revealed that prebiopsy prostate-specific antigen (PSA) level, postrecurrence PSA doubling time, and positive digital rectal examination (DRE) of the prostatic fossa were all statistically significant predictors of a positive biopsy. For the 49 patients subsequently treated with salvage radiation therapy, the overall actuarial 3- and 5-year PSA relapse-free probabilities were 43% and 24%, respectively. Univariate analysis showed no differences in the PSA relapse-free probabilities associated with any pathologic features of the radical prostatectomy specimen, biopsy confirmation of local recurrence, or DRE of the prostatic fossa. In multivariate analysis, controlling for all other variables, preradiation PSA and postrecurrence PSA doubling time measured before radiation were the only statistically significant predictors of outcome. DRE of the prostatic fossa, prebiopsy PSA, and postrecurrence PSA doubling time predict which patients will have biopsy-proven local recurrence. However, response to salvage radiation therapy is associated with postrecurrence PSA doubling time and with preradiation PSA level only. DRE of the prostatic fossa and biopsy confirmation of local recurrence are not associated with salvage radiation outcome.

Atypical Cribriform Lesions on Prostate Biopsy

Atypical cribriform lesions on prostate needle biopsy specimens are rare and difficult to diagnose. Of 574 high-grade prostatic intraepithelial neoplasia (PIN) lesions on needle biopsy seen at our institution over 75 months, we identified 23 consult cases in which the differential diagnosis was cribriform high-grade PIN versus infiltrating cribriform carcinoma. Prebiopsy prostate-specific antigen (PSA) averaged 6.5 ng/mL (range, 0.3 to 37.3). A positive digital rectal examination (DRE) was present in 12 of 22 (55%) patients for whom information was available. Ordinary high-grade PIN was present elsewhere in the biopsy specimens in 32% of cases. The following architectural features of cribriform glands were evaluated: number (mean, 5; range, 1 to 21); largest size (mean, 0.5 mm; range, 0.1 to 1 mm); necrosis (14%); detached cribriform fragments (18%); stromal fibrosis (18%); and bilaterality (22%). Cytologically, there was cellular maturation toward the center of the cribriform glands (45%); identifiable basal cells on hematoxylin and eosin sections (36%); marked nuclear atypia (9%); and mitoses (23%). Nucleoli were not visible in 18% of cases, small in 36%, and prominent in 45%. With a mean follow-up of 13.8 months for those without progression (25.9 months' overall follow-up), a repeat biopsy diagnosis of cancer was seen in 10 of 22 men [by report: Gleason score (Gs) 4 (n = 1); Gs 6 (n = 3); Gs 7 (n = 4); Gs 9 (n = 2); three biopsy specimens showed ductal features]. An additional two men developed bone metastases without biopsy. Overall, 12 of 22 (55%) patients had cancer on follow-up (one patient lost to follow-up). Four clinicopathologic findings predicted carcinoma on follow-up: positive DRE (p = 0.02); positive transrectal ultrasound (p = 0.02); bilateral atypical cribriform glands (p = 0.02); and detached cribriform glands (p = 0.04).

Kinetics of postbiopsy levels of serum free prostate-specific antigen and percent free prostate-specific antigen

Objectives. We evaluated the effects of transrectal ultrasound-guided biopsy of the prostate on serum total and free prostate-specific antigen (PSA) and the free/total PSA ratio and factors affecting variations in PSA levels. Methods. Serum total and free PSA levels and the free/total PSA ratio were determined in 48 men (mean age 66 ± 7 years) before and 1 hour, 8 days, and 30 days after prostate biopsy. At least six cores were taken using a biopsy gun with an 18-gauge needle. The coefficient of variation of PSA was calculated as the postbiopsy/prebiopsy PSA ratio. Changes in PSA levels and the coefficient of variation were studied. Results. Fifteen (31%) of 48 men had adenocarcinoma on biopsy. Total and free PSA values were significantly increased 1 hour and 8 days after biopsy, and both returned to baseline 30 days after biopsy. The free/total PSA ratio was significantly increased (55%) 1 hour after biopsy and significantly decreased (12%) 8 days after biopsy. Thirty days after biopsy, the median of the free/total PSA ratio (18%) was not significantly different from the prebiopsy ratio (16%). The median of the coefficient of variation of the free/total PSA ratio was 3, 0.7, and 1 at 1 hour, 8 days, and 30 days after biopsy, respectively. Age, prostate volume, number of cores, and digital rectal examination and histologic findings were not significantly associated with variation in percent free PSA. Variation in percent free PSA at day 8 was associated with prebiopsy total PSA value and the free/total PSA ratio. Conclusions. Prostate biopsy dramatically alters the percent free PSA. The free/total PSA ratio was decreased 8 days after biopsy and returned to prebiopsy levels in 75% of patients at 1 month after biopsy. Measurement of free PSA levels and the free/total PSA ratio should not be done within 4 weeks of prostate biopsy.

Effect of prostate biopsy on the results of the PSA RT-PCR test

Objectives. To evaluate the effect of prostate biopsy on the prostate-specific antigen (PSA) reverse transcriptase-polymerase chain reaction (RT-PCR) test. Methods. Ninety men who were scheduled to undergo prostate biopsy because of an elevated PSA or abnormal digital rectal examination, or both, were recruited to have PSA RT-PCR performed on peripheral blood samples drawn before and at 30 minutes, 1 week, and 1 month after undergoing prostate biopsy. PSA RT-PCR was performed and all PCR products were blotted and hybridized with phosphorus-32 ( 32-P)-PSA cDNA probe (exon 3 to 5). Results. Of 90 patients, 77 had a negative prebiopsy PSA RT-PCR result. Of these 77, 2 (2.6%) had a positive PSA RT-PCR result at some point after the biopsy procedure. Both of these patients had no evidence of malignancy on biopsy. The PSA RT-PCR test was positive at 30 minutes for 1 patient, but was negative at 1 week; the other was positive at 1 week but the patient did not return for the 1-month sample. Conclusions. Our study indicates that 2.6% of patients with an initially negative PSA RT-PCR will have a positive PSA RT-PCR test after biopsy has been performed. Although this is uncommon, it may have profound implications for those patients in whom it occurs. On the basis of our results, it appears that one should wait longer than 1 week after prostate biopsy before obtaining blood for PSA RT-PCR testing to decrease the likelihood of a spurious PSA RT-PCR result.

COMPARISON OF 3 INVESTIGATIONAL ASSAYS FOR THE FREE FORM OF PROSTATE SPECIFIC ANTIGEN

Purpose 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. Materials and Methods 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, sup [dagger] Dianon Systems sup [double dagger] and Chiron ACS 180 sup [section] 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. Results 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. Conclusions 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.

Positive Prostate Biopsy Rate Consistently Increases with Age at the Same Prostate-Specific Antigen Level in Patients with Normal Digital Rectal Examination

Objectives. To examine the relationship between positive prostate biopsy rates and age over the range of serum prostate-specific antigen (PSA) concentrations of 4 to 10 ng/mL. Methods. The rates for adenocarcinoma were calculated for prostate biopsy specimens received at UroCor Inc., Oklahoma City, Oklahoma between April 1995 and June 1997. The selection criteria were as follows: men between 50 and 79 years of age, normal digital rectal examination (DRE), prebiopsy PSA level between 4.01 and 10.0 ng/mL obtained within a 4-month period prior to receipt of biopsy, and no previous prostate biopsy. Five thousand six cases were selected out of 81,545 prostate biopsy specimens submitted by office-based urologists. The rates of positive prostate biopsies were stratified by age in decade increments and by PSA in increments of 1 ng/mL. The P values were calculated by the chi-square test. Results. The patient mean age was 65.8 years. An overall increase in the positive prostate biopsy rate for men between 50 and 79 years of age as serum PSA increases from 4.01 to 10.0 ng/mL ( P = 0.047) was found; however, this increase was less significant than the increase found in positive biopsy rates caused by age alone ( P <0.0001). Conclusions. Undetected prostate cancer appears to be a major cause of the increasing serum PSA seen with advancing age.

Interstitial iodine-125 radiation without adjuvant therapy in the treatment of clinically localized prostate carcinoma.

This study was designed to evaluate the efficacy of iodine-125 interstitial radiation in the treatment of prostate carcinoma classified as T1 or T2. One hundred twenty-six consecutive patients with adenocarcinoma of the prostate (T1, 23%; T2, 77%) were treated with iodine-125 radionuclides between January 1, 1988, and December 31, 1990. Four patients died of intercurrent illness within 1 year postimplant, leaving 122 men in the study. The prescribed minimum radiation dose was 160 gray. Median follow-up was 69.3 months. Prebiopsy prostate specific antigen (PSA) values (median, 5.0 ng/mL) were available for all patients. Posttherapy evaluation included clinical, biochemical (PSA), and pathologic (repeat needle biopsy) studies. No patient was surgically staged, and none received androgen deprivation therapy. Morbidity was graded according to the Radiation Therapy Oncology Group grading scale. Statistical appraisal was performed by the Kaplan-Meier method. PSA failure was defined in two ways: (1) PSA progression, i.e., 2 consecutive increases from a nadir value; and (2) failure to attain an arbitrary serum PSA value of 1.0 or 0.5 ng/mL at last follow-up. The overall 7-year survival was 77%; there were no deaths from prostate carcinoma in this cohort. The 7-year actuarial PSA progression free outcome was 89%, and the PSA < or = 1.0 ng/mL outcome was 87%. When PSA < or = 0.5 ng/mL was selected as an outcome end point, and PSA values in this series of radiation-treated patients were compared with PSA values proposed to indicate disease free survival after radical prostatectomy (PSA < or = 0.3-< or = 0.6 ng/mL), the 7-year actuarial disease free survival was 79%. Morbidity was minimal except in patients who had preimplant or postimplant transurethral prostate resection. Outpatient-based iodine-125 prostate brachytherapy for prostate carcinoma classified as T1 or T2 resulted in biochemical outcomes comparable to end points resulting from radical prostatectomy and external beam radiation.

Inflammation in Benign Prostatic Hyperplasia: Correlation With Prostate Specific Antigen Value

We attempted to identify morphological parameters of benign prostatic hyperplastic inflammation that correlate with pre-biopsy prostate specific antigen (PSA) concentrations. Patients undergoing prostate biopsy at our department were prospectively studied between January 1995 and January 1996. preoperative blood and 24-hour urine samples were measured for PSA. Biopsy samples harboring exclusively benign prostatic tissue were graded on a 4-point scale for inflammation (0-no inflammatory cells, 1-scattered inflammatory cell infiltrate, 2-nonconfluent lymphoid nodules and 3-large inflammatory areas with confluence of infiltrate) and aggressiveness (0-no contact between inflammatory cells and glandular epithelium; 1-contact between inflammatory cell infiltrate and glandular epithelium; 2-clear but limited, that is less than 25% of the examined material, glandular epithelium disruption, and 3-glandular epithelium disruption on more than 25% of the examined material). A total of 66 patients with exclusively benign prostatic tissue on prostate biopsies was analyzed. Difference between inflammation graded groups was not significant when considering serum or urinary PSA. There was a significant correlation between aggressiveness grading and serum PSA (rho = 0.51, p < 0.0001), whereas aggressiveness grading and urinary PSA did not correlate (rho = -0.06, p = 0.6). Prostatic subclinical inflammation is not associated with high urinary PSA. Unless associated with glandular epithelial disruption, density of prostatic interstitial inflammatory cell infiltrate is not significantly correlated with serum PSA concentration. We believe that this issue should be considered when interpreting a prostate biopsy.

Experience with an assay for prostate-specific antigen and transrectal ultrasonography in the diagnosis of prostate cancer.

To assess the detection of prostate cancer using the Ciba Corning ACS 180 prostate-specific antigen (PSA) assay and transrectal ultrasonography (TRUS) in a district general hospital. In a preliminary study, the serum PSA level in 130 patients was measured using both the Ciba Corning and the Hybritech Tandem-R PSA assay and the results assessed using linear regression analysis. A further study comprised 204 consecutive patients who underwent TRUS and biopsy. The histology of the prostatic biopsies was analysed according to the pre-biopsy PSA level (Ciba Corning assay), digital rectal examination (DRE) and TRUS findings. The PSA levels measured using the Ciba Corning assay were about 50% higher than those using the Hybritech Tandem-R assay. Of 204 men who had TRUS and biopsy. 56 (28%) had detectable prostate cancer, but no patient with a PSA of < 6.0 ng/mL had. Five of 47 (11%), 21 of 83 (25%) and 30 of 65 (46%) patients with PSA levels in the range 6.1-15.15.1-30 and > 30 ng/mL, respectively, had cancer detected. When the DRE was negative, 18 of 111 (16%) patients had a positive biopsy, compared with 38 of 93 (41%) patients when the DRE was positive (P < 0.001). In men with a PSA level of 6.1-15.0 ng/mL, positive biopsies were found in 3% when the DRE was negative, compared with 27% when it was positive (P < 0.025). A TRUS abnormality was detected in 54 of 204 (26%) patients, of whom 25 (46%) had positive biopsies. Of these 54, there were 43 with hypoechoic lesions, of whom 22 (51%) had positive biopsies. The cancer detection rate was higher when both TRUS and DRE were positive (62%), with the highest detection rate (86%) occurring when the PSA level was also > 30.0 ng/mL. When the DRE was positive, cancer was detected in 21 of 34 (62%) patients with a positive TRUS, but only in 17 of 59 (29%) patients with a negative TRUS (P < 0.005). However, when the DRE was negative there was no significant difference in the cancer detection rates for TRUS-positive and TRUS-negative patients, where four of 20 and 14 of 91 (15%) patients were found to have cancer, respectively. The positive biopsy rates in this study were comparable with those from similar studies using other PSA assays. When the DRE was negative there was a low detection rate for cancer of 3% for men with PSA levels of 6.1-15.0 ng/mL. In patients with an elevated PSA level but a negative DRE, the positive biopsy rate for TRUS-negative patients did not differ from TRUS-positive patients, indicating the importance of random systematic biopsies.