Sextant prostate biopsies predict side and sextant site of extracapsular extension of prostate cancer

PURPOSE: We examined the ability of sextant prostate biopsies in combination with other preoperative data to predict side and sextant site of prostate cancer extracapsular extension in a large cohort of patients. MATERIALS AND METHODS: We examined 223 contemporary cases of prostate cancer managed by radical prostatectomy. Using logistic regression analysis, we determined whether patient age, Gleason score, clinical stage, prostate specific antigen, number of positive sextants, biopsy location or percent of biopsy cores positive for cancer in a sextant site, side and overall gland was predictive of location of pathological extracapsular extension into periprostatic tissue. RESULTS: Of 41 of the 223 (18%) patients with nonorgan confined disease extracapsular extension was localized to 45 sextant sites in 36 (apex 8, mid 22, base 15) while only side of extension was known in 5. In a multivariate analysis the best predictors of the risk of extracapsular extension on a side were average percent biopsy cores positive for cancer overall 15 or greater (odds ratio 8.4, p <0.0001) and average from 3 ipsilateral biopsies 15 or greater (odds ratio 7.4, p <0.0001). When used in combination these 2 factors yielded a model with a positive predictive value of 37% and a negative predictive value of 95%. Sextant specific percent biopsy cores positive for cancer was predictive of risk of extracapsular extension in a sextant (odds ratio 2.5, p = 0.020). CONCLUSIONS: Our data demonstrate that average overall and per side percent biopsy cores positive for cancer is a significant predictor of risk of extracapsular extension on a side. Sextant specific percent biopsy cores positive for cancer is predictive of sextant site of extension. The high negative predictive value of the side specific model identifies patients who are good candidates for nerve sparing surgery.     

Prediction of indolent prostate cancer: validation and updating of a prognostic nomogram

PURPOSE: Screening with serum prostate specific antigen testing leads to the detection of many prostate cancers early in their natural history. Statistical models have been proposed to predict indolent cancer. We validated and updated model predictions for a screening setting. MATERIALS AND METHODS: We selected 247 patients with clinical stage T1C or T2A from the European Randomized Study on Screening for Prostate Cancer who were treated with radical prostatectomy. We validated a nomogram that had previously been developed in a clinical setting. Predictive characteristics were serum prostate specific antigen, ultrasound prostate volume, clinical stage, prostate biopsy Gleason grade, and total length of cancer and noncancer tissue in biopsy cores. Indolent cancer was defined as pathologically organ confined cancer 0.5 cc or less in volume without poorly differentiated elements. Logistic regression was used to update the previous model and examine the contribution of other potential predictors. RESULTS: Overall 121 of 247 patients (49%) had indolent cancer, while the average predicted probability was around 20% (p <0.001). Effects of individual variables were similar to those found before and discriminative ability was adequate (AUC 0.76). An updated model was constructed, which merely recalibrated the nomogram and did not apply additional predictors. CONCLUSIONS: Prostate cancers identified in a screening setting have a substantially higher likelihood of being indolent than those predicted by a previously proposed nomogram. However, an updated model can support patients and clinicians when the various treatment options for prostate cancer are considered.     

Validation of a nomogram for predicting positive repeat biopsy for prostate cancer

PURPOSE: We reported a nomogram and subsequently a corrected version for predicting the probability of positive biopsy in men with 1 or more prior negative biopsies. In this study we assessed the validity of this nomogram when applied to an external dataset. MATERIALS AND METHODS: There were 230 patients from the Brooklyn Veterans Administration Medical Center who underwent 1 or more repeat biopsies after initial negative biopsy from January 1993 to June 2003. Predictor variables studied in the nomogram were patient age, family history of prostate cancer, digital rectal examination, serum prostate specific antigen, prostate specific antigen slope, months from initial negative biopsy session, months from previous negative biopsy session, cumulative number of negative cores previously taken and history of high grade intraepithelial neoplasm or atypical small acinar proliferation. We calculated the nomogram predicted probability in each patient. These predicted outcomes were compared with actual biopsy results. Area under the ROC curve was calculated as a measure of discrimination. Calibration was assessed graphically. RESULTS: We evaluated a total of 356 repeat biopsies in 230 patients (mean 2.56 total biopsies per patient). The mean number of total cores per patient was 17.9. There were 78 positive biopsies. The area under the ROC curve was 0.71, which was greater than any single risk factor. Nomogram calibration appeared to be good. CONCLUSIONS: Our corrected nomogram for predicting positive repeat biopsy performed well when applied to a sample of men at the Brooklyn Veterans Administration Medical Center. This nomogram can provide important additional information to aid the urologist and patient with a negative biopsy in evaluating clinical options.     

A validated strategy for side specific prediction of organ confined prostate cancer: a tool to select for nerve sparing radical prostatectomy

PURPOSE: Nerve sparing radical prostatectomy for prostate cancer should be restricted to patients who harbor tumors without capsular penetration. To our knowledge the selection criteria for nerve sparing radical prostatectomy are not clearly defined. We investigated a panel of preoperative tumor characteristics with respect to their ability to predict organ confined tumor growth for each lobe of the prostate to indicate unilateral or bilateral nerve sparing radical prostatectomy. MATERIALS AND METHODS: Nine preoperative tumor characteristics in 278 patients with clinically localized prostate cancer were included in retrospective univariate and multivariate tree structured regression analysis. The association of clinical stage, serum prostate specific antigen (PSA), PSA density, and results of transrectal ultrasound and systematic sextant biopsy, including a quantitative assessment of cancer in the biopsies with organ confined tumor growth, was statistically evaluated. Except for serum PSA and PSA density preoperative characteristics were considered separately for each prostate lobe. Multivariate analysis results were validated prospectively in 353 patients. RESULTS: On univariate analysis the number of positive biopsies was the most useful single parameter with a positive predictive value of 83% in 274 lobes and a negative predictive value of 55%, followed by mm. of tumor in the biopsy. Of all characteristics included in multivariate analysis only the number of biopsies with high grade cancer, the number of positive biopsies and serum PSA were independent for predicting organ confined cancer. When PSA was less than 10 ng./ml. and not more than 1 biopsy with high grade cancer was identified in a lobe, organ confined tumor growth was present in 86.1% of cases. On prospective validation the same criteria led to an 88.5% incidence of organ confined prostate cancer. Pooling the 2 most favorable groups led to 391 prostate lobes (70.8% of those investigated) with a positive predictive value of 82.1% (95% confidence interval 77.9% to 85.8%). Using the multivariate approach more prostate lobes were assigned to a favorable risk group than on univariate analysis. Clinical stage and simple Gleason grade did not contribute independent information for predicting organ confined disease. CONCLUSIONS: Quantifying cancer and high grade cancer by systematic biopsy and serum PSA concentration are useful preoperative characteristics for predicting organ confined prostate cancer. Side specific analysis of these parameters is a flexible and reliable tool for selecting patients for nerve sparing radical prostatectomy.     

Diagnostic value of systematic biopsy methods in the investigation of prostate cancer: a systematic review

PURPOSE: Several new extended prostate biopsy schemes (greater than 6 cores) have been proposed. We compared the cancer detection rates and complications of different extended prostate biopsy schemes for diagnostic evaluation in men scheduled for biopsy to identify the optimal scheme. MATERIALS AND METHODS: In a systematic review we searched 13 electronic databases, screened relevant urological journals and the reference lists of included studies, and contacted experts. We included studies that compared different systematic prostate biopsy methods using sequential sampling or a randomized design in men scheduled for biopsy due to suspected prostate cancer. We pooled data using a random effects model when appropriate. RESULTS: We analyzed 87 studies with a total of 20,698 patients. We pooled data from 68 studies comparing a total of 94 extended schemes with the standard sextant scheme. An increasing number of cores were significantly associated with the cancer yield. Laterally directed cores increased the yield significantly (p = 0.003), whereas centrally directed cores did not. Schemes with 12 cores that took additional laterally directed cores detected 31% more cancers (95% CI 25 to 37) than the sextant scheme. Schemes with 18 to 24 cores did not detect significantly more cancers. Adverse events for schemes up to 12 cores were similar to those for the sextant pattern. Adverse event reporting was poor for schemes with 18 to 24 cores. CONCLUSIONS: Prostate biopsy schemes consisting of 12 cores that add laterally directed cores to the standard sextant scheme strike the balance between the cancer detection rate and adverse events. Taking more than 12 cores added no significant benefit.     

Evaluation of a novel precision template-guided biopsy system for detecting prostate cancer

OBJECTIVE

To explore the ability of a novel transrectal ultrasonography (TRUS) device (TargetScan^TM, Envisioneering Medical Technologies, St. Louis MO) that creates a three‐dimensional map of the prostate and calculates an optimal biopsy scheme, to accurately sample the prostate and define the true extent of disease, as standard TRUS‐guided prostate biopsy relies on the operator to distribute the biopsy sites, often resulting in under‐ and oversampling regions of the gland.

PATIENTS AND METHODS

In a multicentre retrospective chart review evaluating patients who had a TargetScan prostate biopsy between January 2006 and June 2007, we determined the overall cancer detection rate in all patients and in subgroups based on prostate specific antigen level, digital rectal examination, and indication for biopsy. We assessed the pathological significance of cancer detected, defined as a Gleason score of ≥7, positive margins, extracapsular disease or >20% tumour volume in the prostatectomy specimen. We also evaluated the concordance in Gleason score between the biopsy and prostatectomy specimen.

RESULTS

Cancer was detected in 50 (35.7%) of the 140 patients biopsied, including 39 (47.6%) with no previous biopsies. Of 23 prostatectomy specimens, 20 (87%) had pathologically significant disease. The biopsy predicted the prostatectomy Gleason score in 12 patients (52%), overestimated in two (9%), underestimated in eight (35%), and biopsy Gleason score could not be assigned in one (4%).

CONCLUSIONS

Template‐guided biopsy potentially produces a higher cancer detection rate and more accurate assessment of grade. Prostatectomy specimens did not have a high rate of pathologically insignificant disease.     

Predicting the outcome of prostate biopsy: comparison of a novel logistic regression‐based model,the prostate cancer risk calculator,and prostate‐specific antigen level alone

OBJECTIVES

To develop a logistic regression‐based model to predict prostate cancer biopsy at, and compare its performance to the risk calculator developed by the Prostate Cancer Prevention Trial (PCPT), which was based on age, race, prostate‐specific antigen (PSA) level, a digital rectal examination (DRE), family history, and history of a previous negative biopsy, and to PSA level alone.

PATIENTS AND METHODS

We retrospectively analysed the data of 1280 men who had a biopsy while enrolled in a prospective, multicentre clinical trial. Of these, 1108 had all relevant clinical and pathological data available, and no previous diagnosis of prostate cancer. Using the PCPT risk calculator, we calculated the risks of prostate cancer and of high‐grade disease (Gleason score ≥7) for each man. Receiver operating characteristic (ROC) curves for the risk calculator, PSA level and the novel regression‐based model were compared.

RESULTS

Prostate cancer was detected in 394 (35.6%) men, and 155 (14.0%) had Gleason ≥7 disease. For cancer prediction, the area under the ROC curve (AUC) for the risk calculator was 66.7%, statistically greater than the AUC for PSA level of 61.9% (P < 0.001). For predicting high‐grade disease, the AUCs were 74.1% and 70.7% for the risk calculator and PSA level, respectively (P = 0.024). The AUCs increased to 71.2% (P < 0.001) and 78.7% (P = 0.001) for detection and high‐grade disease, respectively, with our novel regression‐based models.

CONCLUSIONS

ROC analyses show that the PCPT risk calculator modestly improves the performance of PSA level alone in predicting an individual’s risk of prostate cancer or high‐grade disease on biopsy. This predictive tool might be enhanced by including percentage free PSA and the number of biopsy cores.     

B超引导10点前列腺穿刺法诊断前列腺癌的结果分析

目的探讨经直肠超声引导下10点法前列腺穿刺活检中前列腺癌阳性结果的分布情况。方法本组473例均因PSA>4ng/ml而进行经直肠超声引导下10点法宝前列腺穿刺活检,穿刺点为在标准的系统6点(前列腺旁正中线矢状切面尖部、中部、底部)的基础上,两外侧各增加2针(外侧周缘中部、底部)。本组患者年龄为41～85岁,平均65岁;PSA水平4.1～444ng/ml,平均15.05ng/ml;前列腺体积8.0～160.0ml,平均42.17ml。对穿刺各针的阳性率及各区域独立出现的阳性率进行分析。结果穿刺总阳性率为26.6%(126/473)。前列腺各穿刺部位的阳性率为:外侧底部23.7%(112/473)、外侧中部20.7%(98/473)、底部19.5%(92/473)、中部18.4%(87/473)、尖部23.9%(113/473)。只有该区域出现阳性的分布情况:外侧底部8.7%(11/126)、外侧中部5.6%(7/126)、底部2.4%(3/126)、中部3.2%(4/126)、尖部7.1%(9/126)。各穿刺部位的阳性率具有统计学差异(P<0.01)。结论经直肠超声引导下经直肠前列腺10点法穿刺活检术可明显提高前列腺癌的临床检出率。其前列腺的尖部、外侧底部和外侧中部的穿刺阳性率要比其他部位高。     

The extent of biopsy involvement as an independent predictor of extraprostatic extension and surgical margin status in low risk prostate cancer: implications for treatment selection

PURPOSE: We identify predictors of extraprostatic extension and positive surgical margins in patients with low risk prostate cancer (prostate specific antigen [PSA] 10 ng./ml. or less, biopsy Gleason score 7 or less and clinical stage T1c-2b). MATERIALS AND METHODS: From August 1997 to January 1999, 143 previously untreated patients underwent radical retropubic prostatectomy for clinically localized prostate cancer. A total of 62 patients were low risk, with PSA 10 ng./ml. or less, biopsy Gleason score 7 or less and clinical stage T1c-2b, and had sextant biopsy with separate pathological evaluation of each sextant cores. PSA, clinical stage, biopsy Gleason score, average percentage of cancer in the entire biopsy specimen, maximum percentage of cancer on the most involved core, number of cores involved and bilaterality were evaluated for association with extraprostatic extension, seminal vesicle involvement and positive surgical margins. RESULTS: Of the 62 patients 13 (21%) had extraprostatic extension, 6 (10%) seminal vesicle involvement and 20 (32%) positive surgical margins. Average percentage greater than 10% and maximum percentage greater than 25% were associated with extraprostatic extension (p = 0.01 and 0.004, respectively). Average percentage greater than 10%, maximum percentage greater than 25%, more than 2 cores involved and bilaterality were associated with positive surgical margins (p = 0.007, 0.01, 0.002 and 0.03, respectively). On multivariate analysis maximum percentage remained the only independent predictor of extraprostatic extension (p = 0.03), and the number of cores involved remained an independent predictor of positive surgical margins (p = 0.01). Biopsy Gleason score, PSA and clinical stage did not correlate with extraprostatic extension or positive surgical margins in this patient population. CONCLUSIONS: In low risk prostate cancer the extent of biopsy involvement significantly correlates with the risk of extraprostatic extension and positive surgical margins. Biopsy information should be considered when selecting and modifying treatment modalities.     

Improved clinical staging system combining biopsy laterality and TNM stage for men with T1c and T2 prostate cancer: results from the SEARCH database

PURPOSE: A number of studies have failed to show significant differences in outcome following radical prostatectomy between men with palpable, clinically localized prostate cancer (cT2) and those whose tumors are not palpable (cT1c). We determined whether we could improve the prognostic value of the TNM staging system in men with cT1c and cT2 cancers by including information on whether prostate needle biopsy was unilaterally or bilaterally positive. MATERIALS AND METHODS: A retrospective survey of 992 patients from the SEARCH (Shared Equal Access Regional Cancer Hospital) Database treated with radical prostatectomy at 4 equal access medical centers between 1988 and 2002 was done. TNM 1992 clinical stage was T1c in 421 patients, T2a in 287, T2b in 202 and T2c in 82. Multivariate analysis was used to examine whether biopsy laterality and clinical stage were significant predictors of surgical margin status, nonorgan confined disease, seminal vesicle invasion, and time to prostate specific antigen (PSA) recurrence following radical prostatectomy. RESULTS: Patients with clinical stages T2b and T2c cancers had similar rates of PSA recurrence, which were significantly higher than in patients with T1c and T2a disease, who also had similar rates of PSA recurrence. Bilateral positive biopsy further stratified patients with T1c and T2a disease (p = 0.01) but not those with T2b and T2c cancers (p = 0.207). Grouping these 1992 clinical stages with biopsy laterality resulted in a new clinical staging system, which was a significant predictor of PSA recurrence following radical prostatectomy (p <0.001). On multivariate analysis whether TNM clinical stage was evaluated as a categorical or continuous variable only PSA, biopsy Gleason score and the new clinical staging system (1992 TNM stage groupings combined with biopsy laterality) were significant independent predictors of time to biochemical recurrence following radical prostatectomy. CONCLUSIONS: Combining low (T1c and T2a) and high (T2b and T2c) risk 1992 clinical stages with biopsy laterality (unilateral versus bilateral positive) resulted in a new clinical staging system that was a stronger predictor of PSA recurrence following radical prostatectomy than the 1992 or 1997 TNM clinical staging system. If confirmed at other centers and in men who undergo with other treatment modalities, consideration should be given to revising the current TNM staging system to reflect these findings.     

Clinical value of prostate specific antigen based parameters for the detection of prostate cancer on repeat biopsy: the usefulness of complexed prostate specific antigen adjusted for transition zone volume

PURPOSE: To our knowledge the indications for repeat prostate needle biopsy in men whose previous transrectal ultrasound guided biopsy results revealed no evidence of cancer have not yet been defined. We identified the most effective method for detecting prostate cancer on repeat biopsy. MATERIALS AND METHODS: One or more systematic repeat prostate biopsies were performed in 144 consecutive patients, including 86 with prostate specific antigen (PSA) levels between 4 and 10 ng./ml. at repeat biopsy. Men in whom cancer was detected on repeat biopsies were compared with their counterparts in terms of digital rectal examination findings, PSA based parameters and an atypical prostate on initial prostate biopsy. RESULTS: Prostate cancer was detected on repeat biopsy in 39 of the 144 patients and in 19 on subset analysis of 86. Serum PSA levels at repeat biopsy did not differ significantly in patients with and without prostate cancer. According to receiver operating characteristics analysis the alpha1-antichymotrypsin-PSA complex adjusted for transition zone volume had the greatest area under the curve values, that is 0.756 for all 144 patients and 0.768 for the subset analysis of 86. Multiple logistic regression analysis of the subset of 86 patients showed that alpha1-antichymotrypsin-PSA complex adjusted for transition zone volume was the only significant independent predictor of cancer. CONCLUSIONS: alpha1-Antichymotrypsin-PSA complex adjusted for transition zone volume was the most powerful predictor of cancer in men who had undergone previous negative prostate biopsies. This parameter may be used to avoid more unnecessary repeat biopsies with an acceptable decrease in sensitivity.     

Assessment of the enhancement in predictive accuracy provided by systematic biopsy in predicting outcome for clinically localized prostate cancer

PURPOSE: Current localized prostate cancer treatment outcome nomograms rely on prostate specific antigen (PSA), tumor stage and grade. We investigated whether the addition of prostate biopsy features may enhance the accuracy of a nomogram predicting recurrence after radical prostatectomy (RP). MATERIALS AND METHODS: Clinical data from 1,152 patients who underwent RP were used and included PSA, clinical stage, biopsy Gleason grade and systematic biopsy information that quantified the amount of cancer and high grade cancer. Predictive accuracy for freedom from recurrence after RP was assessed with and without tumor quantification in the biopsy by the area under the receiver operating characteristics curve (AUC). RESULTS: Percentage and number of cores with cancer, and percentage and number of cores with high grade cancer were predictors of outcome when added to models that included PSA, Gleason grade and clinical stage (all p <0.0001). Nomogram accuracy with 3 traditional variables (AUC 0.790) was minimally enhanced with the addition of percentage or number of positive cores (AUC 0.804 and 0.800, respectively), or percentage or number of cores with high grade cancer (AUC 0.802 and 0.800, respectively). Maximum predictive accuracy of 0.811 was achieved after supplementing the traditional 3-variable nomogram with various combinations of additional pathological predictors. CONCLUSIONS: The information provided by systematic biopsies substantially improves the ability to predict outcome following RP. However, some incremental predictive accuracy was achieved by adding systematic biopsy features.     

Effects of systematic 12-core biopsy on the performance of percent free prostate specific antigen for prostate cancer detection

PURPOSE: The performance characteristics of percent free (f) prostate specific antigen (PSA) for differentiating between benign prostatic hyperplasia and prostate cancer were originally established using primarily sextant biopsy. We determined whether the addition of 6 laterally directed cores to the traditional sextant prostate biopsy affects the performance of percent fPSA. MATERIALS AND METHODS: We retrospectively evaluated a cohort of 350 consecutive biopsies in men with negative digital rectal examinations and PSA between 4 and 10 ng/ml who underwent systematic 12 core biopsy (S12C) biopsy at Scott Department of Urology between March 1999 and January 2003. The effects of 6 additional, laterally directed biopsies on the sensitivity, specificity and area under the ROC curve for percent fPSA was evaluated in the 277 men in whom percent fPSA was measured. RESULTS: Cancers detected exclusively in the 6 laterally directed cores were associated with percent fPSA values similar to those in patients with a benign S12C biopsy. This resulted in a modest and yet predictable decrease in the sensitivity of percent fPSA at each biopsy threshold value without affecting specificity. There was a nonstatistically significant decrease in the area under the ROC curve with the addition of 6 laterally directed cores to sextant biopsy (medial sextant cores 0.66 vs S12C 0.60). CONCLUSIONS: The 12 core biopsy strategies have a higher cancer detection rate than sextant biopsies and they are gaining widespread acceptance. The addition of 6 laterally directed cores to traditional sextant biopsy may result in a modest decrease in the sensitivity of percent fPSA at each selected biopsy threshold without affecting specificity.     

Prostate saturation biopsy in the reevaluation of microfocal prostate cancer

PURPOSE: We evaluated the ability of an extended, 32-core repeat transrectal ultrasound prostate biopsy protocol to improve the characterization of low volume, well differentiated disease in men with a diagnosis of potentially insignificant microfocal prostate cancer, as defined by 1 single focus positive core of 10 with less than 5 mm of Gleason score 6 or less tumor on primary biopsy. MATERIALS AND METHODS: A total of 35 consecutive patients, who were 62 to 75 years old, had a median serum prostate specific antigen of 8 ng/ml (range 0.5 to 14) and a diagnosis of minimal prostate cancer, and were willing to consider observation with delayed treatment at progression, were offered repeat saturation prostate biopsy with a median of 32 cores (range 18 to 36) under local anesthesia. This biopsy was to determine whether more extensive prostate sampling would confirm or disprove the initial diagnosis of microfocal, well differentiated prostate cancer. RESULTS: The procedure was aborted in 1 patient because of massive rectal hemorrhage. Another patient had acute prostatitis with gram-negative sepsis. Of 34 evaluable biopsy sets 11 (32%) were negative for cancer, suggesting that tumor detected at the primary biopsy was probably of low volume and amenable to observation with delayed treatment. Of the biopsies 23 (68%) were positive, 17 were at multiple sites and 7 were upgraded to Gleason score 7 or greater. These patients were then considered to have significant tumors and were offered active treatment. CONCLUSIONS: This study is to our knowledge the first to describe the clinical use of prostate saturation biopsies for re-evaluating potentially insignificant prostate cancer. Of patients with minimal disease on standard 10-core biopsy, results show that this technique may be helpful for distinguishing the 30% who probably have minimal disease based on negative repeat saturation biopsy from the 70% who almost certainly have a significant tumor, as characterized by multiple positive cores, with or without an increased Gleason score. The latter patients should be offered active therapy.     

经直肠超声引导前列腺穿刺活检术诊断前列腺癌

目的　总结和评价经直肠超声引导下前列腺穿刺活检术对前列腺癌诊断的准确率。方法　222 例直肠指检阳性或 PSA>4μg/L的患者应用经直肠超声引导下前列腺6点系统穿刺活检以明确诊断。结果　222 例受检者中病理证实前列腺结节性增生41例、前列腺炎24例、前列腺肉瘤3例、前列腺癌 154 例,其中低分化癌 74 例、中分化癌 58 例、高分化癌 22 例。术后血尿15例、发热6例,其中高热1例,经抗生素治疗后体温恢复正常、尿检阴性。结论　经直肠超声引导下前列腺穿刺活检无需麻醉,患者痛苦小、安全性高,是诊断前列腺癌的可靠方法。     

Serial biopsy results in prostate cancer screening study

PURPOSE: We evaluated prostate biopsy results in men with elevated prostate specific antigen (PSA) levels and/or suspicious digital rectal examination whose initial biopsies did not reveal cancer. MATERIALS AND METHODS: A total of 2,526 volunteers 40 years old or older underwent 1 or more prostate biopsies for serum PSA concentrations greater than 4.0 ng./ml. (before May 1995) or greater than 2.5 ng./ml. (after May 1995), or digital rectal examination suspicious of cancer. We evaluated compliance with the biopsy recommendation and the cancer detection rate with regard to digital rectal examination results and increasing PSA levels. RESULTS: Of the men who underwent up to 10 biopsy procedures the serial cancer detection rates were 29%, 17%, 14%, 11%, 9% and 7%, respectively, on biopsy procedures 1 through 6. No significant difference in the yield of cancer on serial biopsies was observed between the groups using the greater than 4.0 ng./ml. and greater than 2.5 ng./ml. cutoff. There was a trend for more cancers detected through serial screening to be organ confined compared with those detected on initial screening (78% versus 69%, p = 0.05). Also, more cancers detected using the greater than 2.5 ng./ml. cutoff were organ confined (80% versus 66%, p = 0.004). Only approximately 1% of the cancers fulfilled the published criteria for clinically insignificant tumors. CONCLUSIONS: Nearly a quarter of prostate cancers detected in this screening study were missed by the initial biopsy. Of the 962 prostate cancers detected 77% were detected with 1, 91% with 2, 97% with 3 and 99% with 4 biopsy procedures. Serial biopsies detect more organ confined cancers without over detecting clinically unimportant tumors. Future studies are needed to determine whether obtaining more biopsy cores initially would provide earlier prostate cancer detection and avoid unnecessary repeat biopsies.     

Prostate specific antigen adjusted for transition zone epithelial volume: the powerful predictor for the detection of prostate cancer on repeat biopsy

PURPOSE: The indications for repeat prostate biopsy for persistently increased prostate specific antigen (PSA) in men with prostate cancer never detected on previous biopsy are not clear. In this study we determined that PSA adjusted for transition zone (TZ) epithelial volume is the most powerful predictor for detecting prostate cancer on repeat biopsy. MATERIALS AND METHODS: Repeat prostate biopsies including additional TZ cores were performed in 75 men with PSA between 4.0 and 10.0 ng/ml. TZ epithelial volume was calculated by multiplying TZ volume by the percent of epithelium, which was measured by morphometric analysis using image analysis computer software. RESULTS: Prostate cancer was detected on repeat biopsy in 19 of the 75 patients. Patients with prostate cancer had a significant smaller percent area of epithelium or glandular lumen than those without cancer. In patients without prostate cancer TZ epithelial volume significantly correlated with total PSA. According to ROC analysis PSA adjusted for TZ epithelial volume had the greatest AUC for cancer detection (0.879). This parameter was able to avoid more than 90% of unnecessary repeat biopsies with 90% sensitivity. Multiple logistic regression analysis showed that PSA complex adjusted for TZ epithelial volume was the significant independent predictor of cancer. CONCLUSIONS: PSA adjusted for TZ epithelial volume is the most powerful predictor of cancer in men who have undergone previous negative prostate biopsies and in whom PSA remains between 4.0 and 10.0 ng/ml.