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。     

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.     

Prostate cancer detection with office based saturation biopsy in a repeat biopsy population

PURPOSE: Patients at increased risk for prostate cancer with previously negative biopsies pose a diagnostic challenge. We have previously demonstrated that extensive saturation biopsy can be performed in an office setting. We now report the diagnostic yield of office saturation biopsy in patients at increased risk for prostate cancer and at least 1 negative prior biopsy. MATERIALS AND METHODS: We performed saturation prostate biopsy with local anesthesia in the office in 116 patients with at least 1 prior negative biopsy and with certain risk factors, namely persistently elevated prostate specific antigen, abnormal digital rectal examination, or prior atypia or PIN on prior biopsy. RESULTS: A total of 34 cancers were detected for an overall diagnostic yield of 29%. A 64% detection rate was noted when a patient had undergone a single prior sextant biopsy. Subgroup analysis revealed a cancer detection rate of 41% when only prior sextant biopsies were performed, and a 24% detection rate when 10 or more cores were taken on prior biopsy. The detection rate was 33% when only 1 prior biopsy was taken and it was 24% when 2 or more prior biopsies were performed. CONCLUSIONS: Saturation biopsy can be performed safely and effectively in the office with a significant diagnostic yield even in patients with previous extended biopsy schemes. We believe that it should be the next diagnostic step after an initial negative biopsy in patients in whom the diagnosis of prostate cancer is strongly suspected.     

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.     

Use of extended pattern technique for initial prostate biopsy

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.     

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.     

Development and external validation of an extended repeat biopsy nomogram

PURPOSE: We hypothesized that the outcome of repeat biopsy could be accurately predicted. We tested this hypothesis in a contemporary cohort from 3 centers. MATERIALS AND METHODS: The principal cohort of 1,082 men from Hamburg, Germany was used for nomogram development as well as for internal 200 bootstrap validation in 721 and external validation in 361. Two additional external validation cohorts, including 87 men from Milan, Italy and 142 from Seattle, Washington, were also used. Predictors of prostate cancer on repeat biopsy were patient age, digital rectal examination, prostate specific antigen, percent free prostate specific antigen, number of previous negative biopsy sessions and sampling density. Multivariate logistic regression models were used to develop the nomograms. RESULTS: The mean number of previous negative biopsies was 1.5 (range 1 to 6) and the mean number of cores at final repeat biopsy was 11.1 (range 10 to 24). Of the men 370 (30.2%) had prostate cancer. On multivariate analyses all predictors were statistically significant (p < or =0.028). After internal validation the nomogram was 76% accurate. External validation showed 74% (Hamburg), 78% (Milan) and 68% (Seattle) accuracy. CONCLUSIONS: Relative to the previous nomograms (10 predictors or 71% accuracy) our tool relies on fewer variables (6) and shows superior accuracy in European men. Accuracy in American men is substantially lower. Racial, clinical and biochemical differences may explain the observed discrepancy in predictive accuracy.     

Improved detection of clinically significant, curable prostate cancer with systematic 12-core biopsy

PURPOSE: While systematic 12-core (S12C) biopsy detects more cancers than sextant biopsy, to our knowledge the clinical significance of these additionally detected tumors has not been established. We studied pathological parameters of prostatectomy specimens from patients undergoing radical prostatectomy for prostate cancer detected with a S12C biopsy to determine the clinical significance of these cancers in comparison with sextant detected cancers. MATERIALS AND METHODS: A total of 179 consecutive patients undergoing radical prostatectomy for clinically localized prostate cancer detected by S12C biopsy were studied. The groups compared consisted of the sextant core subset of the S12C and the entire S12C set. Total tumor volume, Gleason score, organ confined status, surgical margin status, seminal vesicle invasion, lymph node involvement, and clinical significance of tumors detected by sextant and by S12C templates were compared. RESULTS: S12C biopsy detected a greater number of cancers scored as moderate (Gleason score 2 to 6) or high (Gleason score 7 or greater) grade, and cancers of all sizes regardless of organ confined status than the sextant cores alone (all p <0.05). S12C biopsy identified a greater number of biologically significant and insignificant tumors regardless of how they were defined. CONCLUSIONS: Compared with the sextant set S12C biopsy detects a significantly greater number of surgically curable, biologically significant tumors as well as those that might be considered clinically insignificant.     

Short-term prophylaxis with ciprofloxacin in extended 16-core prostate biopsy

Objective

To evaluate the safety, efficacy and possible complications of 16-core transrectal prostate biopsies using two doses of ciprofloxacin for prophylaxis of infectious complications.

Materials and Methods

Sixteen-core prostate biopsies were performed on a number of patients with different signs of potential prostate cancer. Complications were assessed both during the procedure and one week later. After the procedure, urine samples were collected for culture. The rate of post-biopsy complications, hospital visits and hospitalizations were also analyzed. Ciprofloxacin (500 mg) was administered two hours before, and eight hours after the procedure.

Results

The overall rate of post-biopsy complications was 87.32%, being 5.4% of those considered major complications due to hemorrhage, or to urinary retention. Eight patients required hospital treatment post-biopsy. Fever occurred in just one patient (0.29%). There was no incidence of orchitis, epididymitis, prostatitis, septicemia, hospitalization, or death. The urine culture showed positive results in five patients (2.15%).

Conclusion

One-day prophylaxis with ciprofloxacin proved to be safe and effective in the prevention of infectious complications following 16-core prostate biopsies.     

Optimising repeat prostate biopsy decisions and procedures

What's known on the subject? and What does the study add? Due to the fear of missing clinically significant cancer, it is often uncertain whether a repeat biopsy should be performed in men with ≥1 prior negative prostate biopsies but persistent suspicion of prostate cancer. However, the repeat biopsy may again be negative and a biopsy may be associated with anxiety, discomfort and complications (resulting in hospitalisation in 4.1% of men). This review discusses strategies to optimise repeat biopsy procedures in order to better predict the biopsy outcome. Optimising repeat biopsy procedures include adjusting the location and number of cores and the use of MRI to detect suspicious areas. The use of diagnostic markers, e.g. (Prostate CAncer) gene 3, which is predictive of biopsy outcome, can aid in guiding repeat biopsy decisions and reduce the number of unnecessary and uncomfortable biopsies. To review strategies to optimise repeat biopsy procedures and to better predict the biopsy outcome. As it is often uncertain whether a repeat biopsy should be performed in men with ≥1 previous negative prostate biopsies but persistent suspicion of prostate cancer. The repeat biopsy may also be negative and a biopsy may be associated with anxiety, discomfort and occasionally (severe) complications. A search in PubMed was performed to find English language original and review articles related to repeat prostate biopsies. Strategies to optimise repeat biopsy procedures include applying the appropriate indications and adjusting the location and number of biopsy cores. The PROGENSA? Prostate CAncer gene 3 (PCA3) Assay is a highly prostate cancer‐specific test. A higher PCA3 Score corresponds with an increased probability of a positive repeat biopsy and including the PCA3 Score in multivariate models significantly increased their predictive accuracy for predicting repeat biopsy outcome. The PCA3 Score seems also to be predictive of future biopsy outcome. In clinical practice it is often uncertain whether a prostate biopsy should be repeated or not. Optimising repeat biopsy procedures and the use of diagnostic markers, such as PCA3, can increase the probability of a positive repeat biopsy and reduce the number of unnecessary and uncomfortable biopsies     

Limitations of biopsy Gleason grade: implications for counseling patients with biopsy Gleason score 6 prostate cancer

PURPOSE: We examined the implications of underestimating Gleason score by prostate biopsy in patients with biopsy Gleason 6 prostate cancer with respect to adverse pathological findings and biochemical recurrence after radical prostatectomy. MATERIALS AND METHODS: We retrospectively reviewed clinical and pathological data on a cohort of 531 patients with Gleason score 6 on prostate biopsy who underwent radical retropubic prostatectomy between June 1992 and January 2002. Patients were excluded if they received neoadjuvant androgen deprivation. Concordance between biopsy and radical prostatectomy Gleason score was examined. A comparison was made with respect to final radical prostatectomy specimen pathology and the risk of biochemical recurrence between cases that remained Gleason 6 and those with a final grade of 7 or greater. RESULTS: A total of 451 patients were included in the analysis. Mean followup was 55.1 months (range 12 to 123.4). Of the patients 184 (41%) had a Gleason score of 7 or greater after a review of the entire prostate, while 37 (8%) had a score of less than 6 and 230 remained with Gleason 6. Patients who were under graded were more likely to have extraprostatic extension (22% vs 4%, p <0.01), seminal vesicle invasion (9% vs 2%, p <0.01) and biochemical recurrence (10% vs 3%, p <0.01) compared to those who remained with Gleason score 6. CONCLUSIONS: Gleason grade on needle biopsy is an inexact predictor of the final grade following radical prostatectomy. Patients with biopsy Gleason score 6 who are under graded are at significantly higher risk for adverse pathological features and biochemical recurrence than patients who remain with Gleason score 6 or less on final pathology findings.     

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。     

Individualized prostate biopsy strategy for Chinese patients with different prostate-specific antigen levels

Aim： To evaluate the best individualized prostate biopsy strategies for Chinese patients with suspected prostate cancer. Methods： The present study included 221 Chinese patients who underwent transrectal ultrasound guided prostate biopsies for the first time. All patients underwent the same 10-core biopsy protocol. In addition to the Hodge sextant technique, four more biopsies were obtained from the base and middle regions of bilateral peripheral zones. The differences between 10-core and sextant strategies in cancer detection among patients with different prostate specific anitgen （PSA） levels were evaluated. The relationship between PSA level, number of positive biopsy cores and organ-confined cancer rate in prostate cancer patients was also analyzed. Results： The overall prostate cancer detection rate was 40.7% in the 221 patients. The 10-core strategy increased cancer detection by 6.67% （6/90） in our patients （P 〈 0.05）. The increased cancer detection rates decreased significantly when the patient PSA level increased from 0-20 ng/mL to 20.1-50 ng/mL and 〉 50 ng/mL （P 〈 0.01）. The number of positive biopsy cores in prostate cancer patients increased significantly with increasing patient PSA level （P 〈 0.01）. The rate of organ-confined prostate cancer decreased significantly with increasing patient PSA level （P 〈 0.01）. Conclusion： The extended 10- core strategy is recommended for Chinese patients with PSA 〈 20 ng/mL and the sextant strategy is recommended for those with PSA〉 50 ng/mL. For patients with PSA ranging from 20.1 ng/mL to 50 ng/mL, the 10-core strategy should be applied in patients with life expectancy 〉 10 years and the sextant strategy should be applied in those with life expectancy 〈 10 years. （Asian J Androl 2008 Mar; 10： 325-331）