Predicting tumour location in radical prostatectomy specimens: same‐patient comparisons of 21‐sample versus sextant biopsy

OBJECTIVE

To determine the value of a 21‐sample biopsy protocol in predicting tumour localization in radical prostatectomy (RP) specimens, compared with sextant biopsies.

PATIENTS AND METHODS

In all, 300 consecutive patients underwent 21‐sample prostate biopsies, followed by RP. The protocol consisted of sextant, three midline, six far lateral and six transitional zone biopsies. Tumour locations on biopsies and RP specimens were compared. The sensitivity, specificity, positive (PPV) and negative predictive value (NPV) and accuracy were calculated.

RESULTS

There was no difference between sextant and 21‐sample biopsies for sensitivity (38% vs 36%; P = 0.50) and specificity (84% vs 87%; P = 0.46), but the NPV was higher for 21‐sample biopsies (57% vs 68% ; P < 0.001). The PPV was higher in the sextant biopsies (74% vs 59%; P = 0.007). Sextant, transitional zone and far lateral biopsies were re‐grouped in six regions. Compared with 21‐sample biopsies, sensitivity (54%) and PPV (79%) were higher (P < 0.001), while specificity (74%) and NPV (46%) were lower (P = 0.05 and P = 0.001, respectively).

CONCLUSION

A negative biopsy does not confirm the absence of cancer in the corresponding site in the RP specimen in a sextant or 21‐sample biopsy protocol and cannot be used as a prognostic element before RP. A positive biopsy does not always correspond with a tumour in the same zone of the RP specimen. When 21‐sample biopsies are re‐grouped in to six regions, the value of a positive biopsy increases. A positive biopsy corresponds thus to a tumour in the same region, rather than in precisely the same location. The results of this study could help in the biopsy protocol used for making surgical decisions, e.g. preserving the bladder neck or neurovascular bundles.     

The role of transrectal saturation biopsy in tumour localization: pathological correlation after retropubic radical prostatectomy and implication for focal ablative therapy

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? The traditional transrectal sextant and extended biopsy schemes demonstrated low accuracy in predicting unilateral prostate cancer on radical prostatectomy specimens. We examined the accuracy of an initial saturation biopsy (24‐core) to predict unilateral prostate cancer on radical prostatectomy specimens.

OBJECTIVE

• ? To evaluate the accuracy of an initial 24‐core prostate biopsy scheme (PBx24) in predicting unilateral prostate cancer (PCa) in radical prostatectomy (RP) specimens.

PATIENTS AND METHODS

• ? Between 2005 and 2008, 203 consecutive patients underwent PBx24 followed by RP for PCa. The area under the curve (AUC) was used to evaluate the accuracy of unilateral PCa on PBx24 to predict unilateral PCa in RP specimens.
• ? The positive predictive value (PPV) and negative predictive value (NPV) were also calculated. Moreover, in patients with unilateral PCa on biopsy, univariable and multivariable logistic regression analyses tested the relationship between the presence of unilateral PCa in an RP specimen and the variables: age, prostate‐specific antigen (PSA), total prostate volume, clinical stage, primary Gleason grade, secondary Gleason grade and the number of positive cores.

RESULTS

• ? PCa cores were unilateral in 115 patients (56.7%) on biopsy. Of those, only 26 (22.6%) had unilateral PCa in the RP specimen (AUC, 72.9%; PPV, 22.6%; NPV, 98.8%). In patients with clinically low‐risk tumours, only 17 of 63 (27%) had a unilateral PCa on PBx24 and in the RP specimen (AUC, 59.1%; PPV, 27.0%; NPV, 100.0%).
• ? None of the examined variables was an independent predictor of the presence of unilateral PCa in the RP specimen (all P > 0.05).

CONCLUSIONS

• ? Initial PBx24 is not sufficiently accurate to be dependable as a method of predicting tumour laterality in RP specimens. Therefore, the use of PBx24 to guide hemi‐ablation therapy of PCa may lead to mistreatment in a considerable proportion of patients.
• ? Moreover, none of the routinely available clinical and pathological characteristics appears to improve the ability of unilateral PCa on biopsy to predict unilateral PCa in the RP specimen.

     

Systematic 5 Region Prostate Biopsy is Superior to Sextant Method for Diagnosing Carcinoma of the Prostate

Purpose

The number of patients undergoing prostate biopsy has dramatically increased due to prostate specific antigen screening. The low specificity of this screening tool requires prostate biopsy for diagnosis of prostate cancer. The sextant biopsy technique has been used widely with success in diagnosing carcinoma of the prostate. However, concern has arisen that the original sextant method may not include an adequate sampling of the prostate. For many years we have used a method of prostate biopsy that, in addition to sextant biopsies, takes additional biopsies in a systematic fashion, which we call the 5 region prostate biopsy. We conducted a prospective study to determine if our 5 region prostate biopsy technique significantly increases the chances of finding carcinoma of the prostate compared to the sextant biopsy technique.

Materials and Methods

A total of 119 patients underwent transrectal ultrasound guided needle biopsy of the prostate. In addition to sextant biopsies, cores were taken from the far lateral and mid regions of the gland. Pathological findings of the additional regions were compared to those of the sextant regions.

Results

Of the 48 patients with prostate cancer 17 (35%) had carcinomas only in the additional regions, which would have remained undetected had the sextant biopsy technique been used alone (p <0.05). Of these additional cancers 83% had Gleason scores of 6 or more.

Conclusions

We introduce the 5 region technique of prostate biopsy as a means of significantly increasing the diagnostic yield of prostate biopsy in finding carcinoma of the prostate. We have found this technique to be safe, efficacious and superior to the sextant method of biopsy in identifying prostate cancer at an early but significant stage. The greatest use of the 5 region biopsy technique is in patients who have prostate specific antigen levels between 4 and 10 ng./ml.     

Comparison of cancers detected at only a sextant or alternative location

OBJECTIVES

To evaluate the effect of the tumour‐positive biopsy site at extended biopsy on tumour volume and potential biological significance of prostate cancer.

PATIENTS AND METHODS

We retrospectively evaluated radical prostatectomy specimens from 247 consecutive men diagnosed with prostate cancer by extended biopsy. Men who had both a positive sextant and alternative site were excluded, resulting in 132 evaluable men. We assessed age, pretreatment prostate‐specific antigen (PSA) level, prostate volume, pathological stage, Gleason score, total tumour volume, and location (sextant or alternative site) of the positive biopsy. Patients were grouped by location of the positive biopsy, i.e. sextant site only or alternative site only, including anterior horn, midline region and transition zone.

RESULTS

A biopsy from a sextant‐only or an alternative site only was positive in 42% (56/132) and 58% (76/132) of men, respectively. There was no significant difference in PSA level, number of positive cores, pathological stage, Gleason score, total tumour volume or the incidence of low‐volume/low‐grade cancer (volume <0.5 mL and a Gleason score of ≤6) between the groups. In men with one positive core, there was no significant difference in total tumour volume (median 0.20 vs 0.36 mL, respectively) or in the incidence of low‐volume/low‐grade cancer (42% vs 40%, respectively) between the groups.

CONCLUSIONS

Total tumour volume and the incidence of low‐volume/low‐grade cancer detected at an alternative site only were comparable to those of cancers detected at a sextant site only. Alternative site biopsy did not increase the incidence of low‐volume/low‐grade cancers detected.     

Does HistoScanning™ predict positive results in prostate biopsy? A retrospective analysis of 1,188 sextants of the prostate

Purpose

The role of HistoScanning? (HS) in prostate biopsy is still indeterminate. Existing literature is sparse and controversial. To provide more evidence according to that important clinical topic, we analyzed institutional data from the Martini-Clinic, Prostate Cancer Center, Hamburg.

Methods

Patients who received prostate biopsy and who also received HS were included in the study cohort. A single examiner, blinded to pathological results, re-analyzed all HS data in accordance with sextants of the prostate. Each sextant was considered as an individual case. Corresponding results from biopsy and HS were analyzed. The area under the receiver-operating characteristic curve (AUC) for the prediction of a positive biopsy by HS was calculated. Furthermore, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were assessed according to different HS signal volume cutoffs (>0, >0.2 and >0.5 ml).

Results

Overall, 198 men were identified and 1,188 sextants were analyzed. The AUC to predict positive biopsy results by HS was 0.58. Sensitivity, specificity, PPV and NPV for HS to predict positive biopsy results per sextant, depending on different HS signal volume cutoffs (>0, >0.2 and >0.5 ml) were 84.1, 27.7, 29.5 and 82.9 %, 60.9, 50.6, 28.8 and 79.7 %, and 40.1, 73.3, 33.1 and 78.8 %, respectively.

Conclusions

Positive HS signals do not accurately predict positive prostate biopsy results according to sextant analysis. We cannot recommend a variation of well-established random biopsy patterns or reduction of biopsy cores in accordance with HS signals at the moment.     

OPTIMIZATION OF PROSTATE BIOPSY STRATEGY USING COMPUTER BASED ANALYSIS

Purpose

We evaluated and optimized the detection of cancer by prostate biopsies. We developed a stochastic computer simulation model of ultrasound guided biopsies using mathematically reconstructed radical prostatectomy specimens. Use of this technique allows rapid evaluation of a variety of factors for their effect on prostate biopsy results. We used this model analyze the effectiveness of sextant biopsies, which have been widely adopted in clinical practice. We also analyzed other biopsy schemes.

Materials and Methods

A total of 607 tumor foci from 180 serially sectioned whole mount radical prostatectomy specimens was mapped and digitized. The cancers had been clinically diagnosed by a variety of biopsy strategies. Simulated parasagittal sextant biopsies were performed for each case. Forty simulation runs (each consisting of a set of 6 biopsies) were performed for each prostate, with realistic random variations in sextant biopsy localization programmed in each run. Cancer detection by biopsy was considered reliable if 90% of the stimulation runs for each prostate were positive for cancer. A summary algorithm was used to map the tumor foci.

Results

Simulation of sextant biopsies demonstrated reliably detected cancer in only 107 of 147 patients (73%) in whom total tumor volume was greater than 0.5 cc. There was little correlation between total length of cancer in biopsy cores and tumor volume. Change of biopsy angle from 30 to 45 degrees did not result in significantly increased detection rates. Similarly, placing all biopsies more laterally did not increase overall detection rates. When we mapped tumor foci from the 40 cases in which sextant biopsies did not reliably detect tumor, we found that the foci were distributed in areas not biopsied by the sextant method, that is the transition zone, midline peripheral zone and inferior portion of the anterior horn of the peripheral zone. A 10-core biopsy scheme incorporating these areas as well as the posterolateral prostate reliably detected cancer in 141 of 147 patients (96%) with total tumor volumes greater than 0.5 cc.

Conclusions

Prostate cancer of significant volume can be present in areas not sampled by standard sextant biopsies. Biopsies of the transition zone, midline peripheral zone and inferior portion of the anterior horn of the peripheral zone should be considered for re-biopsy strategy after negative sextant biopsies. Sampling of these additional areas also can be incorporated in an initial biopsy scheme to increase overall initial rates of detection of prostate cancer.     

Can non‐malignant biopsy features identify men at increased risk of biopsy‐detectable prostate cancer at re‐screening after 4 years?

OBJECTIVES

To identify pathological features in non‐malignant sextant prostate needle biopsies and assess their predictive value for detecting prostate cancer on biopsy 4 years later.

PATIENTS AND METHODS

We selected and reviewed the biopsy specimens of 121 men that were diagnosed as non‐malignant during the first screening round of the European Randomized Study of Screening for Prostate Cancer (ERSPC), Rotterdam section. Of these 61 (50.4%) were positive for cancer during the second round (the result of a matched random sample). The biopsies were indicated by prostate‐specific antigen levels of ≥ 3.0 ng/mL. Specimens were scored for high‐grade prostatic intraepithelial neoplasia (HGPIN), active and chronic inflammation, biopsy core length and glandular core length. The predictive value of the pathological features for detecting prostate cancer after 4 years was assessed.

RESULTS

In the first‐round biopsies the incidence of HGPIN was 7.1%; there was active inflammation in 22.4% and chronic inflammation in 51.0%. The mean core length was 9.3 mm and mean glandular core length 7.4 mm; the mean total biopsy length (sum of core lengths) was 56.3 mm and mean total glandular length (sum of glandular core lengths) was 44.6 mm. None of the pathological features in the initial round was significantly related to the detection of cancer in the second round.

CONCLUSIONS

In this study of non‐malignant prostate biopsy specimens from a screened population, no pathological features could be identified that were predictive for detecting prostate cancer on biopsy 4 years later.     

Risk score predicts high‐grade prostate cancer in DNA‐methylation positive,histopathologically negative biopsies

BACKGROUND

Prostate cancer (PCa) diagnosis is challenging because efforts for effective, timely treatment of men with significant cancer typically result in over‐diagnosis and repeat biopsies. The presence or absence of epigenetic aberrations, more specifically DNA‐methylation of GSTP1, RASSF1, and APC in histopathologically negative prostate core biopsies has resulted in an increased negative predictive value (NPV) of ～90% and thus could lead to a reduction of unnecessary repeat biopsies. Here, it is investigated whether, in methylation‐positive men, DNA‐methylation intensities could help to identify those men harboring high‐grade (Gleason score ≥7) PCa, resulting in an improved positive predictive value.

METHODS

Two cohorts, consisting of men with histopathologically negative index biopsies, followed by a positive or negative repeat biopsy, were combined. EpiScore, a methylation intensity algorithm was developed in methylation‐positive men, using area under the curve of the receiver operating characteristic as metric for performance. Next, a risk score was developed combining EpiScore with traditional clinical risk factors to further improve the identification of high‐grade (Gleason Score ≥7) cancer.

RESULTS

Compared to other risk factors, detection of DNA‐methylation in histopathologically negative biopsies was the most significant and important predictor of high‐grade cancer, resulting in a NPV of 96%. In methylation‐positive men, EpiScore was significantly higher for those with high‐grade cancer detected upon repeat biopsy, compared to those with either no or low‐grade cancer. The risk score resulted in further improvement of patient risk stratification and was a significantly better predictor compared to currently used metrics as PSA and the prostate cancer prevention trial (PCPT) risk calculator (RC). A decision curve analysis indicated strong clinical utility for the risk score as decision‐making tool for repeat biopsy.

CONCLUSIONS

Low DNA‐methylation levels in PCa‐negative biopsies led to a NPV of 96% for high‐grade cancer. The risk score, comprising DNA‐methylation intensity and traditional clinical risk factors, improved the identification of men with high‐grade cancer, with a maximum avoidance of unnecessary repeat biopsies. This risk score resulted in better patient risk stratification and significantly outperformed current risk prediction models such as PCPTRC and PSA. The risk score could help to identify patients with histopathologically negative biopsies harboring high‐grade PCa. Prostate 76:1078–1087, 2016. © 2016 The Authors. The Prostate Published by Wiley Periodicals, Inc.     

Additional Midline Biopsies of the Peripheral Zone Associated with the First Endorectal Standard Sextant Pattern Improves the Accuracy of Prostate Cancer Detection in Japanese Patients

Objectives

This study was designed to estimate the improved accuracy of prostate cancer (PCa) detection resulting from additional midline biopsies of the peripheral zone in first standard biopsy.

Patients and Methods

Patients were classified into 3 groups: 402 cases of sextant biopsies (1995–2002), 488 cases of 8-core biopsies with 2 additional midline biopsies (2003–2006), and 391 cases of 10-core biopsies with 4 additional midline biopsies (2007–2012). The positive rate of each number of biopsies and changes in positive rates associated with prostate specific antigen (PSA) ranges were estimated.

Results

The positive rate of core biopsy significantly improved with increasing numbers of core biopsies (30.1% for sextant, 43.4% for 8-core biopsies, and 53.1% for 10-core biopsies). The accuracy of biopsies for each PSA range also significantly improved (22.3% for sextant, 30.0% for 8-core biopsies, and 43.2% for 10-core biopsies in the PSA gray zone [4.01–10 ng/ml]; and 26.5% for sextant, 52.9% for 8-core biopsies, and 71.8% for 10-core biopsies in the intermediate PSA range [10.1–20 ng/ml]). In the 208 cases with positive results using the 10-core biopsy method, the distribution of Gleason scores did not differ between the sextant only group and the midline site only group.

Conclusions

Additional midline biopsy was associated with improved accuracy of positive core biopsies in Japanese patients with a PSA range of 4.01–20 ng/ml.© 2015 S. Karger AG, BaselKey Words: Additional midline, Diagnosis accuracy, Prostate cancer, First endorectal biopsy, Systematic biopsy     

The association between prostate size and Gleason score upgrading depends on the number of biopsy cores obtained: results from the Shared Equal Access Regional Cancer Hospital Database

OBJECTIVE

To test the hypothesis that the association between prostate size and risk of Gleason grade upgrading varies as a function of sampling.

PATIENTS AND METHODS

We examined the association between pathological prostate weight, prostate biopsy scheme and Gleason upgrading (Gleason ≥7 at radical prostatectomy, RP) among 646 men with biopsy Gleason 2–6 disease treated with RP between 1995 and 2007 within the Shared Equal Access Regional Cancer Hospital Database using logistic regression. In all, 204 and 442 men had a sextant (six or seven cores) or extended‐core biopsy (eight or more cores), respectively. Analyses were adjusted for centre, age, surgery, preoperative prostate‐specific antigen level, clinical stage, body mass index, race, and percentage of cores positive for cancer.

RESULTS

In all, 281 men (44%) were upgraded; a smaller prostate was positively associated with the risk of upgrading in men who had an extended‐core biopsy (P < 0.001), but not among men who had a sextant biopsy (P = 0.22). The interaction between biopsy scheme and prostate size was significant (P interaction = 0.01).

CONCLUSIONS

These data support the hypothesis that the risk of upgrading is a function of two opposing contributions: (i) a more aggressive phenotype in smaller prostates and thus increased risk of upgrading; and (ii) more thorough sampling in smaller prostates and thus decreased risk of upgrading. When sampled more thoroughly, the phenotype association dominates and smaller prostates are linked with an increased risk of upgrading. In less thoroughly sampled prostates, these opposing factors nullify, resulting in no association between prostate size and risk of upgrading. These findings help to explain previously published disparate results of the importance of prostate size as a predictor of Gleason upgrading.     

Contrast‐enhanced ultrasonography using cadence‐contrast pulse sequencing technology for targeted biopsy of the prostate

OBJECTIVE

To evaluate contrast‐enhanced ultrasonography (US) using cadence‐contrast pulse sequencing (CPS) technology, compared with systematic biopsy for detecting prostate cancer, as grey‐scale US has low sensitivity and specificity for detecting prostate cancer.

PATIENTS AND METHODS

In all, 44 men with suspicious prostate‐specific antigen (PSA) levels and CPS findings were assessed; all had CPS‐targeted and systematic biopsy. Transrectal CPS images were taken with a low mechanical index (0.14). A microbubble contrast agent (SonoVue, Bracco International BV, Amsterdam, the Netherlands) was administered as a bolus, with a maximum dose of 4.8 mL. CPS was used to assess prostatic vascularity. Areas with a rapid and increased contrast enhancement within the peripheral zone were defined as suspicious for prostate cancer. Up to five CPS targeted biopsies were taken and subsequently a 10‐core systematic biopsy was taken. Cancer detection rates for the two techniques were compared.

RESULTS

Overall, cancer was detected in 35 of 44 patients (80%), with a mean PSA level of 3.8 ng/mL. Lesions suspicious on CPS showed cancer in 35 of 44 patients (80%) and systematic biopsy detected cancer in 15 of 44 patients (34%). CPS‐targeted cores were positive in 105 of 220 cores (47.7%) and in 41 of 440 systematic biopsy cores (9.3%) (P < 0.001). Lesions suspicious on CPS were false‐positive in nine of 44 patients (20%). The mean Gleason score for systematic biopsy was 6.7 and for CPS‐targeted biopsy 6.8 (P > 0.05). The sensitivity of CPS for detecting cancer was 100% (confidence interval, 95%). However, limitations in the series included that only CPS‐positive cases were investigated, and CPS‐targeted biopsy should be evaluated in a more extended biopsy scheme.

CONCLUSIONS

Contrast‐enhanced US using CPS enables excellent visualization of the microvasculature associated with prostate cancer, and can improve the detection of prostate cancer compared with systematic biopsy.     

Positive predictive value of prostate biopsy indicated by prostate‐specific‐antigen‐based prostate cancer screening: trends over time in a European randomized trial*

Study Type – Diagnosis (validating cohort) Level of Evidence 1b What's known on the subject? and What does the study add? The European Randomized study of Screening for Prostate Cancer (ERSPC) showed a reduction in prostate cancer mortality of 21% for PSA‐based screening at a median follow‐up of 11 years. In the ERSPC, men are screened at 4‐year intervals. A prostate biopsy is recommended for men with a PSA level ≥3.0 ng/mL. The study shows that the positive predictive value (PPV) of a prostate biopsy indicated by PSA‐based screening remains equal throughout consecutive screening rounds in men without a previous biopsy. In men who have previously had a benign biopsy, the PPV drops considerably, but 20% of the cancers detected still show aggressive characteristics.

OBJECTIVE

• ? To assess the positive predictive value (PPV) of prostate biopsy, indicated by a prostate‐specific antigen (PSA) threshold of ≥3.0 ng/mL, over time, in the Rotterdam section of the European Randomized study of Screening for Prostate Cancer (ERSPC).

PATIENTS AND METHODS

• ? In the Rotterdam section of the ERSPC, a total of 42 376 participants, aged 55–74 years, identified from population registries were randomly assigned to a screening or control arm.
• ? For the ERSPC men undergo PSA screening at 4‐year intervals. A total of three screening rounds were evaluated; therefore, only men aged 55–69 years at the first screening were eligible for the present study.

RESULTS

• ? PPVs for men without previous biopsy remained equal throughout the three subsequent screenings (25.5, 22.3 and 24.8% respectively).
• ? Conversely, PPVs for men with a previous negative biopsy dropped significantly (12.0 and 15.2% at the second and third screening, respectively).
• ? Additionally, in men with and without previous biopsy, the percentage of aggressive prostate cancers (clinical stage >T2b, Gleason score ≥7) decreased after the first round of screening from 44.4 to 23.8% in the second (P < 0.001) and 18.6% in the third round (P < 0.001).
• ? Repeat biopsies accounted for 24.6% of all biopsies, but yielded only 8.6% of all aggressive cancers.

CONCLUSIONS

• ? In consecutive screening rounds the PPV of PSA‐based screening remains equal in previously unbiopsied men.
• ? In men with a previous negative biopsy the PPV drops considerably, but 20% of cancers detected still show aggressive characteristics.
• ? Individualized screening algorithms should incorporate previous biopsy status in the decision to perform a repeat biopsy with the aim of further reducing unnecessary biopsies.

     

Evaluation of GSTP1 and APC methylation as indicators for repeat biopsy in a high-risk cohort of men with negative initial prostate biopsies

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Hypermethylation of genes such as glutathione‐S‐transferase P1 (GSTP1) and adenomatous polyposis coli (APC) occurs with high frequency in prostate tumour tissue but is much less common in the benign prostate; however, the potential value of gene methylation biomarkers as an adjunct to biopsy histopathology has had little study. When measured in histologically benign prostate biopsy tissue, APC gene hypermethylation was found to have high negative predictive value and high sensitivity. GSTP1 hypermethylation was found to have lower performance than APC.

OBJECTIVE

• ? To evaluate the performance of DNA methylation biomarkers in the setting of repeat biopsy in men with an initially negative prostate biopsy but a high index of suspicion for missed prostate cancer.

PATIENTS AND METHODS

• ? We prospectively evaluated 86 men with an initial histologically negative prostate biopsy and high‐risk features.
• ? All men underwent repeat 12‐core ultrasonography‐guided biopsy.
• ? DNA methylation of glutathione‐S‐transferase P1 (GSTP1) and adenomatous polyposis coli (APC) was determined using tissue from the initially negative biopsy and compared with histology of the repeat biopsy.
• ? The primary outcome was the relative negative predictive value (NPV) of APC compared with GSTP1, and its 95% confidence interval (CI).

RESULTS

• ? On repeat biopsy, 21/86 (24%) men had prostate cancer.
• ? APC and GSTP1 methylation ratios below the threshold (predicting no cancer) produced a NPV of 0.96 and 0.80, respectively. The relative NPV was 1.2 (95% CI: 1.06–1.36), indicating APC has significantly higher NPV.
• ? Methylation ratios above the threshold yielded a sensitivity of 0.95 for APC and 0.43 for GSTP1.
• ? Combining both methylation markers produced a performance similar to that of APC alone.
• ? APC methylation patterns were consistent with a possible field effect or occurrence early in carcinogenesis.

CONCLUSIONS

• ? APC methylation provided a very high NPV with a low percentage of false‐negatives, in the first prospective study to evaluate performance of DNA methylation markers in a clinical cohort of men undergoing repeat biopsy.
• ? The potential of APC methylation to reduce unnecessary repeat biopsies warrants validation in a larger prospective cohort.

     

Incremental value of transition zone and midline apical biopsy at baseline TRUS-guided biopsy for prostate cancer detection

Purpose

To determine the diagnostic yield of transition zone (TZB) and midline apical biopsies (MAB) in baseline transrectal ultrasound (TRUS)-guided biopsies and to establish whether TZB and MAB for the diagnosis of prostate cancer (PCa) add clinical relevant information.

Methods

We performed baseline 9-core TRUS-guided biopsy in 412 consecutive subjects using sextant biopsies of the PZ (PZB), with an additional TZB on either side and a MAB at the prostatic apex. We determined the incremental diagnostic value of additional TZB an MAB to sextant PZB.

Results

Within a cohort of 412 patients with a median PSA of 7.5 ng/ml, 178 (43.2 %) patients were diagnosed with PCa upon baseline TRUS-guided biopsies. In 102 cases, at least one TZB was positive for PCa, with 6/412 (1.4 %) cases displaying PCa in the TZB only. MAB alone was positive for PCa in 4/412 (1.0 %) cases. One case (1/412; 0.2 %) had only a TZB and a MAB positive for PCa without positive PZB. Thus, 11/412 (2.7 %) of cases would not have been diagnosed with PCa at baseline TRUS-guided biopsy had only sextant PZ biopsy been performed. TZB detected a high-grade Gleason component (Gleason 4 and/or 5) not present in the PZB in 2.4 % of PCa cases.

Conclusions

There is limited value for TZB and MAB in the context of sextant PZB at baseline TRUS-guided biopsies for PCa.     

Repeat prostate biopsies predict location of index cancer in an active surveillance cohort

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? The accuracy of TRUS‐guided biopsies in identifying the location of an index cancer at surgery is low. When two biopsies show cancer in the same location, the concordance between the biopsy and surgical location of the cancer increases.

OBJECTIVE

? To evaluate the ability of repeat prostate biopsies to determine the location of the index cancer for men on prostate cancer surveillance.

PATIENTS AND METHODS

? Forty‐five men on active surveillance had a record of the locations of their positive diagnostic biopsy, repeat surveillance biopsy and index cancer (i.e. largest cancer) from prostatectomy specimens. ? Logistic regression analysis was used to evaluate the association between two consecutive needle biopsies showing cancer in an identical location and the outcome of finding the index cancer at the same location as the initial diagnostic biopsy.

RESULTS

? Eighteen of 45 (40%) men ultimately had an index cancer at the same location as their diagnostic biopsy. ? Thirteen men had two consecutive biopsies that showed cancer at the same location each time; nine of these men ultimately had an index cancer at that same location. ? In multivariable logistic regression analysis of men with at least two biopsies, having two initial consecutive biopsies with the same location increased the odds (odds ratio 5.9; 95% CI 1.1–31, P= 0.037) of having an index cancer at the same location as the initial biopsy in a cohort of men on active surveillance.

CONCLUSIONS

? A substantial proportion of men in an active surveillance cohort who undergo prostatectomy ultimately have evidence of an index cancer at the same location as their initial biopsy. ? This is more likely to be the case when a repeat biopsy shows evidence of cancer at the same location.     

Transrectal ultrasonography-guided biopsy does not reliably identify dominant cancer location in men with low-risk prostate cancer

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? The widespread use of serum PSA testing followed by TRUS‐guided biopsy have resulted in profound prostate cancer stage migration with many patients presenting with focal rather than multifocal disease. There is increasing interest in the use of focal rather than whole‐gland treatment. However, current biopsy schemes may still miss cancer or, even when cancer is identified, its extent or grade might not be accurately characterized. In order for focal therapy to be effective, the area of highest tumour volume and/or grade needs to localized accurately. The aim of this study was to assess how well biopsy, as currently performed, locates the focus of highest prostate cancer volume and/or grade.

OBJECTIVE

• ? To evaluate the ability of transrectal ultrasonography (TRUS)‐guided extended core biopsy to identify the dominant tumour accurately in men with early stage prostate cancer.

PATIENTS AND METHODS

• ? Patients with early stage, low‐risk prostate cancer who subsequently underwent radical prostatectomy (RP) and had complete surgical specimens were identified.
• ? Re‐review was performed by a single uropathologist using ImageJ software to identify tumour location, dominant grade (DG) and dominant volume (DV).
• ? Pathology findings were then compared with biopsy results.

RESULTS

• ? A total of 51 men with early stage, low‐risk prostate cancer, who had undergone RP, had complete specimens for review and a median of 15 biopsy cores taken for diagnosis and grading.
• ? Sixteen men had a single diagnostic biopsy, 21 had one repeat biopsy, and 14 had two or more repeat biopsies.
• ? Compared with surgical findings, biopsy correctly identified the sextant with the largest tumour volume in 55% (95% CI 0.5–0.6) of specimens and the highest grade in 37% (95 CI 0.3–0.5).
• ? No demographic or clinical factors were significantly associated with identification of DG. Interval between last biopsy and RP, total tissue length taken and total length of tumour identified were significantly associated with correct identification of DV.

CONCLUSIONS

• ? Our findings show that TRUS‐guided biopsy detects and localizes DV better than it does DG.
• ? Even with an extended scheme, TRUS‐guided biopsy does not reliably identify dominant cancer location in this low‐risk cohort of men with early stage prostate cancer.
• ? TRUS‐guided biopsy may perform better in similar men with low stage, but higher volume disease.

     

Does the transrectal ultrasound probe influence prostate cancer detection in patients undergoing an extended prostate biopsy scheme? Results of a large retrospective study

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? The influence of transrectal probe system, end‐fire and side‐fire, has not been studied in detail. Using a sextant biopsy template it has been demonstrated a difference between end‐fire and side‐fire modes in 4–10 ng/mL PSA interval population. No studies evaluated the results in extended biopsy templates before. This study adds the knowledge that end‐fire and side‐fire transrectal probe, which are the two probe systems to perform transrectal prostate biopsy, have similar results in terms of prostate cancer detection rate and can be indifferently employed in extended prostate biopsy templates used in daily practice.

OBJECTIVE

• ? To compare the prostate cancer detection rate and tolerance profile between a transrectal biopsy made with a ‘side fire’ (SF) and an ‘end fire’ (EF) ultrasound probe.

PATIENTS AND METHODS

• ? We selected patients undergoing first biopsy and re‐biopsy of the prostate with a 14‐ and 18‐core template using EF and SF transrectal probes, respectively.
• ? We compared the cancer detection rate between the two probes on first biopsy and re‐biopsy and gauged patient tolerance using a visual analogue scale (VAS).

RESULTS

• ? A total of 1705 patients were included in the first biopsy group, while 487 were in the re‐biopsy group.
• ? The overall detection rate of first biopsy was 37.2%; the overall detection rate of re‐biopsy was 10.1%.
• ? No significant difference was found between the two probes in the first biopsy and re‐biopsy sets (38% vs 36.5%, P= 0.55; 10.8% vs 9.3%, P= 0.7).
• ? The lack of any significant association between the type of probe used and prostate cancer detection was confirmed by univariable and multivariable analyses in both the first biopsy and re‐biopsy sets after accounting for prostate‐specific antigen values, per cent free prostate‐specific antigen, digital rectal examination, and prostate and transition zone volumes.
• ? The patient tolerance profile of the SF group was significantly better than that of the EF group (mean VAS 1.78 ± 2.01 vs 1.45 ± 2.21; P= 0.02).

CONCLUSION

• ? The prostate cancer detection rate does not depend on the type of probe used. However, the SF transrectal probe is associated with a better patient tolerance profile.

     

Extended 21-sample needle biopsy protocol for diagnosis of prostate cancer in 1000 consecutive patients

OBJECTIVE: To prospectively evaluate the diagnostic yield of a 21-sample ultrasound-guided needle biopsy protocol as the initial diagnostic strategy for detection of prostate cancer. MATERIALS AND METHODS: Between December 2001 and October 2005, 1000 consecutive patients underwent 21-sample needle biopsies under local anesthesia, comprising sextant biopsies, 3 additional posterolateral biopsies in each peripheral zone, 3 biopsies in each transition zone (TZ), and 3 biopsies in the midline peripheral zone. Each prostate core was numbered and analyzed separately. The patients were divided into subgroups according to the result of digital rectal examination (DRE), serum prostate-specific antigen (PSA), and prostate volume. We evaluated the cancer detection rate overall and in each subgroup. We compared the results of our biopsy protocol to those from 6-, 12-, and 18-core biopsy protocols by analyzing only those cores from our protocol that would correspond to these biopsy schemes. RESULTS: Cancer detection rates using 6 biopsy samples (sextant biopsies only), 12 samples (sextant plus lateral biopsies), 18 samples (sextant, lateral, and TZ biopsies), and 21 samples (sextant, lateral, TZ, plus midline biopsies) were 31.7%, 38.7%, 41.5%, and 42.5%, respectively. The 12-sample procedure improved the cancer detection rate by 22% compared with the 6-sample procedure (p=0.0001). The improvement in the diagnostic yield was most marked in patients with a prostate volume > or =55 ml (36.9%), in patients with normal DRE (26.6%), and in patients with PSA<4 (37.5%). The addition of TZ biopsies to a 12-biopsy scheme increased the diagnostic yield by 7.2% overall (p=0.023). Only 10 of 425 (2.3%) patients were diagnosed on the sole basis of midline biopsies. CONCLUSIONS: Patients with suspected localized prostate cancer should be offered at least 12 biopsies in the peripheral zone and far lateral peripheral zone (statistically significant). TZ biopsies have to be considered, because these biopsies improve the diagnostic yield. For patients with abnormal DRE and/or PSA> or =20 ng/ml, the 6-biopsy scheme seems sufficient (statistically), but 6 far lateral peripheral zone biopsies as well as the TZ biopsies add little incremental value (not significant). Evidence does not support the use of routine midline peripheral zone needle biopsies in the initial biopsy to enhance the detection of prostate cancer.     

Can contemporary transrectal prostate biopsy accurately select candidates for hemi‐ablative focal therapy of prostate cancer?

OBJECTIVE

To determine if biopsy characteristics can be used to identify men with unilateral prostate cancer on radical prostatectomy (RP) pathological specimens, thereby selecting candidates for hemi‐ablative focal therapy.

PATIENTS AND METHODS

Of 1458 men who had RP from January 2000 to June 2007, we identified 590 of 880 evaluable patients with unilateral disease on their preoperative biopsy. Charts were reviewed to record preoperative prostate‐specific antigen (PSA) level, high‐grade prostatic intraepithelial neoplasia (HGPIN), clinical stage, Gleason score, perineural invasion (PNI), prostate volume, number of positive cores, and percentage of positive cores. Final surgical pathology was evaluated for unilateral cancer. Univariate analysis was used (logistic regression method) to identify independent predictors of unilateral disease on the RP specimen. A subset analysis was done in men with low‐risk disease, defined as clinical stage T1C, Gleason score <7 and a PSA level of <10 ng/mL.

RESULTS

Of 590 men with unilateral disease on biopsy, 163 (27.3%) had unilateral disease on the RP specimen. Pathological features, including HGPIN (P = 0.714), Gleason score (P > 0.608), PNI (P = 0.714), number of positive cores (P = 0.076), percentage of cores positive (P = 0.056), prostate volume (P = 0.285), and PSA level (P = 0.062) did not improve the prediction of unilateral disease. When men with unilateral cancer were further stratified to include only those with low‐risk disease, 28.4% had unilateral disease on the RP specimen. None of the biopsy or clinical features evaluated were predictors of unilateral disease on the RP specimen.

CONCLUSION

Unilateral prostate cancer on biopsy predicts unilateral disease on RP pathology in only 27.6% of cases. The predictive ability is not improved by adding biopsy and clinical characteristics. Additional methods are needed to accurately identify men appropriate for focal therapy.     

Update on prostate biopsy technique

PURPOSE OF REVIEW: Over the past decade, a considerable number of modifications have been made to the techniques for prostate cancer biopsy. In this review, we discuss the developments reported in the literature since January 2003. RECENT FINDINGS: The addition of laterally directed biopsies has enhanced the diagnostic performance of the conventional sextant biopsy approach. Several models of the extended biopsy technique have been introduced that increase the number of cores by combining sextant and lateral biopsies to enhance the cancer detection rate. Several reports have shown that the cancer detection rate decreases as prostate volume increases, compared with an increasing cancer detection rate on repeat biopsy in men with large prostate gland volumes. Other studies have shown that the percentage of positive cores and the total percentage of tumor found at biopsy are significant independent predictors of pathological outcome on multivariate analysis. In randomized, double-blind studies, infiltration of the neurovascular bundles with lidocaine significantly reduces pain associated with extended biopsies. SUMMARY: Current reports have suggested that: (1) extended biopsy schemes decrease the false-negative rate compared with conventional sextant biopsy; (2) laterally directed biopsies from the anterior horn should be included in extended biopsy protocols; and (3) local anesthesia reduces pain associated with extended biopsy.