A prospective, randomized trial comparing the Vienna nomogram to an eight-core prostate biopsy protocol

Study Type – Diagnostic (RCT) Level of Evidence 1b What’s known on the subject? and What does the study add? Several studies have shown that increasing the number of prostate biopsy cores will increase the detection rate of prostate cancer, but also risks overdiagnosing insignificant cancer, particularly in the elderly. Our study suggests that there is no significant advantage in using the Vienna nomogram to determine the number of prostate biopsies to be taken, compared to an eight‐core biopsy protocol.

OBJECTIVE

• ? To compare prostate cancer detection rates using the Vienna nomogram versus an 8‐core prostate biopsy protocol. To compare the complication rates of transrectal prostate biopsy in the two groups.

PATIENTS AND METHODS

• ? In a prospective randomized trial, men with a serum PSA ≥ 2.5 ng/ml were stratified according to serum PSA (I = PSA 2.5–10; II = PSA 10.1–30; III = PSA 30.1–50 ng/mL) and were then randomized to group A (number of cores determined according to the Vienna nomogram) or group B (8‐core prostate biopsy).
• ? Statistical analysis was performed using Student’s t‐test for parametric data, Mann‐Whitney test for nonparametric data and Fisher’s exact test for contingency tables. A two‐tailed p‐value <0.05 was accepted as statistically significant.

RESULTS

• ? In the period July 2006 to July 2009, 303 patients were randomized to group A (n = 152) or group B (n = 151). There were no significant differences in serum PSA, prostate volume, PSA density or post‐biopsy complications between the groups.
• ? The cancer detection rate was lower in group A than in group B for the whole study cohort (35.5% vs 38.4%), for those with PSA < 10 ng/ml (28.1% vs 33%) and for those with prostate volume >50 ml (22% vs 25.8%). These differences were not statistically significant (NSS).

CONCLUSION

• ? These findings suggest that there is no significant advantage in using the Vienna nomogram to determine the number of prostate biopsy cores to be taken, compared to an 8‐core biopsy protocol.

     

When serial prostate biopsy is recommended: most cancers detected are clinically insignificant

Study Type – Disagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Many patients undergo serial biopsy with a low rate of detection of prostate cancer, and the rate of detection declines as more biopsies are pursued. Furthermore, the clinical significance of detected cancer appears to decline as well. It is important to follow all possible methods to detect cancer; however, there should be a parallel consideration for the clinical value for detection of these tumours with low malignant potential. The present study investigated in detail the total rate of cancer detection in serial biopsy and how many of these were deemed clinically insignificant. Moreover, it addressed the impact of detecting premalignant lesions on further detection of cancer in serial biopsy.

OBJECTIVE

• ? Many patients pursue serial prostate biopsies after two consecutive negative biopsy sessions. The objective of this study is to determine the indications of serial prostate biopsy and to compare outcomes, including the risk of detecting clinically insignificant cancer using different biopsy protocols in this highly selected population.

PATIENTS AND METHODS

• ? Most cases of prostate cancer are detected on initial or one repeat biopsy, but persistent suspicion of prostate cancer occasionally leads to serial biopsy, which we define as more than two biopsy sessions. We recently showed that transrectal saturation biopsy (sPBx) significantly increases cancer detection when compared with extended schemes (ePBx) in the initial repeat biopsy (second overall biopsy) population, and that most cases identified are clinically significant.
• ? In the past decade, 479 men underwent 749 repeat prostate biopsies after two prior negative biopsy sessions.
• ? The ePBx group included 347 biopsies with 10–14 cores.
• ? The sPBx group included 402 biopsies with >20 cores.
• ? We analysed overall cancer detection and risk of detecting clinically significant vs insignificant tumours.

RESULTS

• ? Prostate cancer was detected in 15.9% of 749 serial biopsies, representing a cumulative prostate cancer detection rate of 24.8% (119/479 patients).
• ? The sPBx group had a significantly higher detection rate per biopsy session (18.6% vs 12.7%, P= 0.026).
• ? Nevertheless, most positive biopsies 75/119 (63%) revealed clinically insignificant cancer, including 74.6% of cancers detected by sPBx.

CONCLUSION

• ? In men with two prior negative prostate biopsies, prostate cancer detection remains low regardless of clinical indication or transrectal biopsy protocol; most cancers identified are clinically insignificant, suggesting the threshold to repeat biopsy after more than one negative session should be very high.

     

Saturation biopsies on autopsied prostates for detecting and characterizing prostate cancer

OBJECTIVES

To evaluate a 36‐core saturation biopsy scheme on autopsied prostate glands to estimate the detection rate based on the true cancer prevalence, and to compare the cancer features on biopsy with whole‐mount pathological analysis, as saturation biopsies have been proposed as a tool to increase the prostate cancer detection rate, and as a staging tool to identify potentially insignificant cancers before surgery.

MATERIAL AND METHODS

We took 36‐core needle biopsies in 48 autopsied prostates from men who had no history of prostate cancer. The first 18 cores corresponded to an extended biopsy protocol including six cores each in the mid peripheral zone (PZ), lateral PZ and central zone. Six additional cores were then taken in each of these three locations. We compared the histological characteristics of step‐sectioned prostates with the biopsy findings. Tumours were considered clinically insignificant if they were organ‐confined with an index tumour volume of <0.5 mL and Gleason score of ≤6.

RESULTS

The pathological evaluation identified 12 (25%) cases of prostate cancer and 22 tumour foci; seven prostate cancers were significant. Of the 22 tumour foci, 16 (73%) were in the PZ. The first 18 cores detected seven cancers (58%), of which five were clinically significant. The last 18 cores detected four cancers, all of which were already detected by the first 18 cores. Of the five cancers remaining undetected by biopsies, two were clinically significant and three were insignificant. Comparison of the histological characteristics between biopsies and step‐sectioned prostates showed an overestimation of Gleason score by saturation biopsies in three of seven cases.

CONCLUSIONS

The evaluation of saturation biopsies based on the true prevalence of prostate cancer showed no increase in detection rate over a less extensive 18‐core biopsy. Also, saturation biopsies might overestimate the final Gleason score on whole‐mount analysis.     

High detection rate of significant prostate tumours in anterior zones using transperineal ultrasound-guided template saturation biopsy

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Men with persistent suspicion for prostate cancer after previous negative standard transrectal biopsy series are offered saturation biopsy either transrectally or transperineally to increase cancer detection rate. A high‐risk group of men with at least two previous negative transrectal biopsies underwent transperineal template‐guided saturation biopsy. Prostate cancer was detected in 26%, predominantly in the anterior zones. PSA velocity or doubling time were the most powerful factors to predict cancer.

OBJECTIVE

• ? To evaluate the detection rate and the regional location of prostate cancer in men undergoing transperineal template‐guided saturation biopsy (TTSB).

PATIENTS AND METHODS

• ? In all, 92 consecutive men with at least two previous negative transrectal biopsy series who underwent a multiple‐core prostate TTSB at our centre were included in the study.
• ? Univariable and multivariable logistic regression analyses were used to address the relationship between parameters before TTSB and prostate cancer‐detection rate.
• ? Covariates consisted of age at biopsy, free and total prostate‐specific antigen (PSA), prostate volume, digital rectal examination findings, histological findings on previous biopsy, PSA velocity (PSAV), PSA‐doubling time (PSADT) and the number of previous negative biopsy sets.

RESULTS

• ? Prostate cancer was diagnosed in 26% of the men.
• ? A median of 30 cores was taken by TTSB.
• ? Adenocarcinoma in >2 cores was detected in 58.5% and Gleason score ≥7 was detected in 46% of the diagnosed men.
• ? Most of the tumours (83.3%) were found in the anterior zones of the gland, with a significantly higher number of positive cores vs the posterior zones (mean 4.9 vs 1.5, P= 0.015).
• ? PSADT and PSAV were the only independent predictors of prostate cancer detection at multivariate analyses with odds ratios of 0.71 (P= 0.014) and 1.58 (P= 0.025), respectively.

CONCLUSIONS

• ? TTSB has a high prostate cancer‐detection rate, especially in the anterior zones.
• ? Men after at least two previous negative transrectal biopsy series and persistent suspicion of prostate cancer, as evidenced by rapid PSA dynamics, should be offered TTSB.

     

Is sampling transitional zone in patients who had prior negative prostate biopsy necessary?

Objective

To assess the necessity of transitional zone sampling of the prostate during repeat prostate biopsy procedures.

Methods

Patients treated for lower urinary tract symptoms with transurethral resection of the prostate (TURP) from April 2004 to July 2009 whom had at least 1 negative prostate biopsy prior to this treatment were chosen as the study group. A histopathological analysis of surgical specimens was employed to determine cancer detection rates.

Results

A total of 72 patients with the mean age of 66.1, mean prostate-specific antigen (PSA) of 10.4?ng/mL and mean prostate volume of 63.2?cc were included. Of the patients, 50 had 1 biopsy set, 17 had 2 sets, 4 had 3 sets and 1 patient had 4 sets of consecutive biopsies. All biopsy results were negative for prostate cancer. After the analysis of surgical specimens obtained during TURP, cancer was detected in 3 patients (4.2%). Transitional zone sampling during prostate biopsies did not significantly improve the cancer detection rate. Transitional zone sampling was performed in 29 biopsies taken from 20 patients, one of whom (5%) had prostate cancer. The remaining 71 biopsies were taken from 52 patients without transitional zone sampling, and cancer was detected in 2 (3.8%) of them.

Conclusions

Since no significant difference was observed between patient groups (those with and those without transitional zone biopsies) in the detection of prostate cancer in the transitional zone, strategies for increasing the number of cores taken from transitional zone during repeat biopsies should be reconsidered.     

The role of transperineal template prostate biopsies in restaging men with prostate cancer managed by active surveillance

Study Type – Diagnostic (exploratory cohort) Level of Evidence 3b What's known on the subject? and What does the study add? The optimal method of active surveillance in prostate cancer remains unknown. This study is one of the first to report on the role of transperineal template prostate biopsies in active surveillance. It demonstrates that around one third of men are reclassified with more significant prostate cancer at an early stage in their management. This is a higher proportion than reported in contemporary cancers using standard transrectal biopsies for restaging.

OBJECTIVE

• ? To evaluate the role of transperineal template prostate biopsies in men on active surveillance.

PATIENTS AND METHODS

• ? In all, 101 men on active surveillance for prostate cancer underwent restaging transperineal template prostate biopsies at a single centre.
• ? Criteria for active surveillance were ≤75 years, Gleason ≤3+3, prostate‐specific antigen (PSA) ≤15 ng/mL, clinical stage T1–2a and ≤50% ultrasound‐guided transrectal biopsy cores positive for cancer with ≤10 mm of disease in a single core.
• ? The number of men with an increase in disease volume or Gleason grade on transperineal template biopsy and the number of men who later underwent radical treatment were assessed.
• ? The role of PSA and PSA kinetics were studied.

RESULTS

• ? In all, 34% of men had more significant prostate cancer on restaging transperineal template biopsies compared with their transrectal biopsies.
• ? Of these men, 44% had disease predominantly in the anterior part of the gland, an area often under‐sampled by transrectal biopsies.
• ? In the group of men who had their restaging transperineal template biopsies within 6 months of commencing active surveillance 38% had more significant disease.
• ? There was no correlation with PSA velocity or PSA doubling time.
• ? In total, 33% of men stopped active surveillance and had radical treatment.

CONCLUSIONS

• ? Around one‐third of men had more significant prostate cancer on transperineal template biopsies.
• ? This probably reflects under‐sampling by initial transrectal biopsies rather than disease progression.

     

Detection rate and factors predictive the presence of prostate cancer in patients undergoing ultrasonography‐guided transperineal saturation biopsies of the prostate

Study Type – Diagnostic (case series)
Level of Evidence 4

OBJECTIVES

To assess the prostate cancer detection rate and predictive factors for prostate cancer after transrectal ultrasonography (TRUS)‐guided transperineal saturation re‐biopsies of the prostate, using a 24‐core scheme.

PATIENTS AND METHODS

We evaluated 143 consecutive patients undergoing TRUS‐guided transperineal saturation re‐biopsy of the prostate using a 24‐core scheme. The inclusion criteria were a previous negative biopsy and a prostate‐specific antigen (PSA) level of ≥10.0 ng/mL, or of 4.0–10.0 ng/mL with a free/total ratio of <20% or an abnormal digital rectal examination or previous high‐grade prostatic intraepithelial neoplasia (HGPIN) or atypical small acinar proliferation (ASAP).

RESULTS

The mean (sd ) age of the patients was 66.5 (6.1) years and the median (interquartile range) PSA level was 9.0 (6.1–12.8) ng/mL. The number of previous biopsies was one in 59% of patients, two in 26% and three or more in 15%. We detected prostate cancer in 26%, ASAP in 5.6% and HGPIN in 2.1%. The cancer detection rate was 47%, 25.5% and 14% for prostate volumes of <40, 40–60 and ≥60 mL, respectively (P = 0.002). On a multivariate analysis the total prostate volume (40–60 vs <40 mL, hazard ratio 5.683; >60 vs <40 mL, hazard ratio 6.965; P = 0.01) was the only significant predictor of prostate cancer at saturation biopsy.

CONCLUSIONS

TRUS‐guided transperineal saturation re‐biopsy of the prostate using a 24‐core scheme resulted in a high cancer detection rate also in patients who had had two or more previous biopsies. The total prostate volume was the only predictor of prostate cancer.     

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.     

The role of a standardized 36 core template-assisted transperineal prostate biopsy technique in patients with previously negative transrectal ultrasonography-guided prostate biopsies

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Template assisted transperineal biopsy of the prostate has become increasingly popular over the past decade. Several studies have demonstrated that transperineal prostate biopsy (TPB) is associated with an increased rate of cancer detection, increased histological concordance with final prostatectomy samples and an increase in anterior and apical prostate cancers than standard TRUS biopsy. However, interpretation of the literature is difficult due to considerable variation between studies in terms of technique and equipment. We examined a small cohort (n= 40) of patients using a standardized 36 core template assisted TPB technique. We show that utilising this technique is associated with high cancer (68%) detection rate in patients with two previous negative TRUS biopsies. Of patients were found to have anterior gland tumours which would not have been detected by standard TRUS guided biopsy.

OBJECTIVE

? To determine the efficacy and safety of a standardized 36 core template‐assisted transperineal biopsy technique for detecting prostate cancer in patients with previously negative transrectal ultrasonography‐guided prostate biopsies and elevated prostate‐specific antigen (PSA) levels.

PATIENTS AND METHODS

? Between April 2008 to September 2010, a total of 40 patients with a mean (range) age of 63 (49–73) years, a mean (range) elevated PSA level of 21.9 (4.7–87) ng/mL and two previous sets of negative TRUS‐guided prostate biopsies underwent standardized 36 core template‐assisted transperineal prostate biopsies under general anaesthetic as a day case procedure. ? The cancer detection rate and complications for all cases were evaluated.

RESULTS

? In total, 27 of 40 (68%) patients were found to have adenocarcinoma of the prostate, two patients (5.0%) had atypical small acinar proliferation, one had high‐grade prostatic intraepithelial neoplasia (2.5%), four (10%) had chronic active inflammation and six (15%) had benign histology. ? Gleason scores were in the range 6–9, with a median Gleason score of 7. ? There were no cases of urosepsis, urinary tract infections or haematuria. A single patient experienced acute urinary retention, with a subsequent succesful trial without a catheter, and haematospermia was common, although minor.

CONCLUSIONS

? Our standardized 36 core template‐assisted transperineal prostate biopsy technique is safe and associated with a high detection rate of prostate cancer. ? This technique should be considered in patients with elevated PSA levels and previously negative TRUS‐guided prostate biopsies.     

The presence of prostate cancer on saturation biopsy can be accurately predicted

Study Type – Diagnostic (non‐consecutive)
Level of Evidence 3b

OBJECTIVE

To improve the ability of our previously reported saturation biopsy nomogram quantifying the risk of prostate cancer, as the use of office‐based saturation biopsy has increased.

PATIENTS AND METHODS

Saturation biopsies of 540 men with one or more previously negative 6–12 core biopsies were used to develop a multivariable logistic regression model‐based nomogram, predicting the probability of prostate cancer. Candidate predictors were used in their original or stratified format, and consisted of age, total prostate‐specific antigen (PSA) level, percentage free PSA (%fPSA), gland volume, findings on a digital rectal examination, cumulative number of previous biopsy sessions, presence of high‐grade prostatic intraepithelial neoplasia on any previous biopsy, and presence of atypical small acinar proliferation (ASAP) on any previous biopsy. Two hundred bootstraps re‐samples were used to adjust for overfit bias.

RESULTS

Prostate cancer was diagnosed in 39.4% of saturation biopsies. Age, total PSA, %fPSA, gland volume, number of previous biopsies, and presence of ASAP at any previous biopsy were independent predictors for prostate cancer (all P < 0.05). The nomogram was 77.2% accurate and had a virtually perfect correlation between predicted and observed rates of prostate cancer.

CONCLUSIONS

We improved the accuracy of the saturation biopsy nomogram from 72% to 77%; it relies on three previously included variables, i.e. age, %fPSA and prostate volume, and on three previously excluded variables, i.e. PSA, the number of previous biopsy sessions, and evidence of ASAP on previous biopsy. Our study represents the largest series of saturation biopsies to date.     

The successful, sustainable elimination of a waiting list for urology outpatients

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The main goal of a prostate biopsy is to identify clinically relevant prostate cancer with the lowest possible morbidity from the procedure. Through time many have tried different variations in the procedure in an attempt to find the optimal methodology for performing prostate biopsies. These changes include better equipment in helping optimize cancer localizing, varying the number of cores in efforts to improve cancer detection and sampling various areas of the prostate to find cancer that may be hiding. To our knowledge we are the first to describe performing prostate biopsies with keeping the sampling size constant and varying the number of cores based on the size of the prostate. The study adds a variation in the current techniques used for prostate biopsies. In certain situations using a standard number of cores makes obtaining proper sampling of a prostate difficult. We propose a methodology in performing prostate biopsies that will allow for standardization of the tissue per core analyzed thus allowing for an improved sampling of the prostate.

OBJECTIVE

To determine the influence of smoking on the outcomes of patient with urothelial carcinoma of the bladder (UCB) not invading muscle treated with BCG therapy.

MATERIALS AND METHODS

A retrospective chart review was conducted on 623 consecutive patients treated with BCG therapy for high‐grade Ta (n= 219; 35.2%), T1 (n= 215; 34.5%) and/or carcinoma in situ (n= 189; 30.3%). Cigarette smoking status was categorized as (smokers vs non‐smokers) and as (current smokers vs past smokers vs never smokers). In addition, we analyzed the time since smoking cessation as a continuous and categorical variable (smoking cessation after diagnosis vs 0.1–10 years before diagnosis vs more than 10 years before diagnosis). Association with outcomes was examined by univariate and multivariable analyses, adjusting for the effects of age, gender, stage and grade.

RESULTS

The study cohort consisted of 423 males (67.9%) and 200 females (32.1%). Overall, 386 patients (62.0%) were past smokers, 97 (15.6%) were current smokers and 140 (22.5%) had never smoked. In both univariate and multivariable analyses, smoking status by any definition was not associated with the response to BCG therapy, disease recurrence, progression, all‐cause mortality or UCB‐specific mortality. TUR grade was significantly associated with disease progression. TUR stage and BCG response at 6 months were significantly associated with disease recurrence, progression, all‐cause mortality and UCB‐specific mortality.

CONCLUSIONS

Smoking does not appear to affect the response to BCG therapy or long‐term oncological outcomes.     

A MODEL FOR THE NUMBER OF CORES PER PROSTATE BIOPSY BASED ON PATIENT AGE AND PROSTATE GLAND VOLUME

Purpose

The systematic sextant biopsy is currently the gold standard for the tissue diagnosis of prostate cancer. However, it is unknown whether this 6 core approach provides optimal sampling of all prostate glands in men of all ages. The goal of the current study was to determine the appropriate number of cores per prostate biopsy based on patient age and prostate gland volume.

Materials and Methods

Patient age and tumor volume doubling time were used to calculate life threatening, clinically significant tumor volumes at diagnosis for 5-year intervals of patient age. A mathematical model was created to determine the minimum number of cores necessary to identify these life threatening tumor volumes in prostate glands 10 to 80 cm.³ without detecting clinically insignificant cancers.

Results

Younger men and men with larger prostate glands require more than 6 cores to ensure the diagnosis of life threatening prostate cancer. These prostates are currently under sampled by sextant biopsy. In a select group of older men who require fewer than 6 cores sextant biopsy may over sample these prostates and lead to over treatment.

Conclusions

The standard sextant biopsy provides optimal sampling of only a minority of prostate glands. An approach to prostate biopsy based on patient age and prostate gland volume maximizes the detection of clinically significant prostate cancer.     

Colour Doppler and microbubble contrast agent ultrasonography do not improve cancer detection rate in transrectal systematic prostate biopsy sampling

Study Type – Diagnosis (RCT) Level of Evidence 1b What’s known on the subject? and What does the study add? Transrectal gray‐scale ultrasonography guided prostate biopsy sampling is the method for diagnosing prostate cancer (PC) in patients with an increased prostate specific antigen level and/or abnormal digital rectal examination. Several imaging strategies have been proposed to optimize the diagnostic value of biopsy sampling, although at the first biopsy nearly 10–30% of PC still remains undiagnosed. This study compares the PC detection rate when employing Colour Doppler ultransongraphy with or without the injection of SonoVue^TM microbubble contrast agent, versus the transrectal ultrasongraphy‐guided systematic biopsy sampling. The limited accuracy, sensitivity, specificity and the additional cost of using the contrast agent do not justify its routine application in PC detection.

OBJECTIVE

? To compare prostate cancer (PC) detection rate employing colour Doppler ultrasonography with or without SonoVue^TM contrast agent with transrectal ultrasonography‐guided systematic biopsy sampling.

PATIENTS AND METHODS

? A total of 300 patients with negative digital rectal examination and transrectal grey‐scale ultrasonography, with PSA values ranging between 2.5 and 9.9 ng/mL, were randomized into three groups: 100 patients (group A) underwent transrectal ultrasonography‐guided systematic bioptic sampling; 100 patients (group B) underwent colour Doppler ultrasonography, and 100 patients (group C) underwent colour Doppler ultrasonography before and during the injection of SonoVue^TM. ? Contrast‐enhanced targeted biopsies were sampled into hypervascularized areas of peripheral, transitional, apical or anterior prostate zones. ? All the patients included in Groups B and C underwent a further 13 systematic prostate biopsies. The cancer detection rate was calculated for each group.

RESULTS

? In 88 (29.3%) patients a histological diagnosis of PC was made, whereas 22 (7.4%) patients were diagnosed with high‐grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. ? No significant differences were found among the three groups for cancer detection rate (P= 0.329). ? Additionally, low sensitivity, specificity and accuracy of colour Doppler with or without SonoVue^TM contrast agent were found.

CONCLUSIONS

? Prostate cancer detection rate does not significantly improve with the use of colour Doppler ultrasonography with or without SonoVue^TM. ? Although no collateral effects have been highlighted, the combined use of colour Doppler ultrasonography and SonoVue^TM determines adjunctive costs and increases the mean time for taking a single prostate biopsy.     

Does repeat biopsy affect the prognosis of patients with prostate cancer treated with radical prostatectomy? Analysis by the number of cores taken at initial biopsy

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? To date, studies to evaluate clinical significance of prostate cancer detected on repeat biopsy in patients who underwent radical prostatectomy have yielded inconsistent results. The present study confirms that prostate cancer diagnosed after repeat biopsies is related to better pathological outcomes after radical prostatectomy, but not predictive of biochemical recurrence. Additionally, we find that the number of cores taken at initial biopsy do not affect the association between the number of previous biopsies and the prognosis.

OBJECTIVE

• ? To determine whether repeat prostate biopsies are associated with more favourable prognoses compared with diagnosis at initial biopsy in patients who undergo radical prostatectomy for prostate cancer and to determine if this association is affected by the number of cores taken at initial biopsy.

PATIENTS AND METHODS

• ? We reviewed 1147 patients with prostate cancer from 1991 to 2008.
• ? Patients were stratified into two groups by the number of biopsies before diagnosis (initial biopsy vs repeat biopsy: at least two biopsies).
• ? The effects of several variables on pathological outcomes and biochemical recurrence‐free and systemic progression‐free survivals were assessed.

RESULTS

• ? Of the 1147 patients, 1064 (92.8%) were diagnosed with cancer at first biopsy and 83 (7.2%) at repeat biopsy.
• ? Compared with patients diagnosed at initial biopsy, those diagnosed at repeat biopsies were more likely to have a lower clinical stage (cT1c: 79.5% vs 55.5%, P < 0.001) and organ‐confined tumours (78.3% vs 61.3%, P= 0.003), but there was no significant difference in initial biopsy core number (8.3 vs 8.7, P= 0.373).
• ? Five‐year biochemical recurrence‐free and progression‐free survival rates did not show significant differences between the two groups (88.8% vs 82.2%, P= 0.078; 100.0% vs 96.5%, P= 0.105, respectively), and these results were not affected by the number of cores taken at initial biopsy.

CONCLUSIONS

• ? Although prostate cancer diagnosed after repeat biopsies was related to better pathological outcomes after radical prostatectomy, the number of previous biopsies did not predict disease recurrence.
• ? Moreover, the number of cores taken at initial biopsy did not affect these associations.

     

A biopsy simulation study to assess the accuracy of several transrectal ultrasonography (TRUS)-biopsy strategies compared with template prostate mapping biopsies in patients who have undergone radical prostatectomy

Study Type – Diagnostic (validating cohort) Level of Evidence 1b What's known on the subject? and What does the study add? Transrectal ultrasonography (TRUS)‐guided biopsies can miss prostate cancer and misclassify risk in a diagnostic setting; the exact extent to which it does so in a repeat biopsy strategy in men with low–intermediate risk prostate cancer is unknown. A simulation study of different biopsy strategies showed that repeat 12‐core TRUS biopsy performs poorly. Adding anterior sampling improves on this but the highest accuracy is achieved using transperineal template prostate mapping using a 5 mm sampling frame.

OBJECTIVE

• ? To determine the effectiveness of two sampling strategies; repeat transrectal ultrasonography (TRUS)‐biopsy and transperineal template prostate mapping (TPM) to detect and exclude lesions of ≥0.2 mL or ≥0.5 mL using computer simulation on reconstructed three‐dimensional (3‐D) computer models of radical whole‐mount specimens.

PATIENTS AND METHODS

• ? Computer simulation on reconstructed 3‐D computer models of radical whole‐mount specimens was used to evaluate the performance characteristics of repeat TRUS‐biopsy and TPM to detect and exclude lesions of ≥0.2 mL or ≥0.5 mL.
• ? In all, 107 consecutive cases were analysed (1999–2001) with simulations repeated 500 times for each biopsy strategy.
• ? TPM and five different TRUS‐biopsy strategies were simulated; the latter involved a standard 12‐core sampling and incorporated variable amounts of error, as well as the addition of anterior cores.
• ? Sensitivity, specificity, negative and positive predictive values for detection of lesions with a volume of ≥0.2 mL or ≥0.5 mL were calculated.

RESULTS

• ? The mean (sd ) age and PSA concentration were 61 (6.4) years and 8.5 (5.9) ng/mL, respectively.In all, 53% (57/107) had low–intermediate risk disease.
• ? In all, 665 foci were reconstructed; there were 149 foci ≥0.2 mL and 97 ≥ 0.5 mL in the full cohort and 68 ≥ 0.2 mL and 43 ≥ 0.5 mL in the low–intermediate risk group.
• ? Overall, TPM accuracy (area under the receiver operating curve, AUC) was ≈0.90 compared with AUC 0.70–0.80 for TRUS‐biopsy.
• ? In addition, at best, TRUS‐biopsy missed 30–40% of lesions of ≥0.2 mL and ≥0.5 mL whilst TPM missed 5% of such lesions.

CONCLUSION

• ? TPM under simulation conditions appears the most effective re‐classification strategy, although augmented TRUS‐biopsy techniques are better than standard TRUS‐biopsy.

     

Predicting unilateral prostate cancer on routine diagnostic biopsy: sextant vs extended

Study Type – Diagnosis (exploratory cohort)
Level of Evidence 2b

OBJECTIVE

To compare the diagnostic properties of routine office‐based sextant and extended biopsies for unilateral prostate cancer, as validated by final pathology, because focal therapy of prostate cancer is gaining acceptance as a viable treatment option and thus patient selection is of paramount consideration.

PATIENTS AND METHODS

We retrospectively analysed records of patients who had a radical prostatectomy (RP) for biopsy confirmed prostate cancer at our institution between 1990 and 2007. Records with incomplete data were excluded. Diagnostic properties for sextant and extended biopsies were calculated and compared for diagnostic accuracy, sensitivity, specificity, positive and negative predictive values (PPV, NPV) and false‐positive and ‐negative rates.

RESULTS

We identified 882 records (729 sextant, 153 extended biopsies) matching our criteria. Overall, unilateral prostate cancer was confirmed in 151 (16%) of pathological RP specimens. The sensitivity improved from 84.1% to 88.0% on sextant and extended biopsy, respectively. Similarly, the PPV increased from 21.9% to 27.2%, specificity from 37.1% to 53.9% (P < 0.05), and NPV from 91.8% to 95.8% (P < 0.05). These changes are reflected in the decrease in false‐positive rates (from 62.9% to 46.1%) and false‐negative rates (from 15.9% to 12.0%). The overall diagnostic accuracy increased from 49% on sextant to 59% on extended biopsy (P < 0.05).

CONCLUSIONS

Taking more prostate biopsy cores improves the diagnostic properties for identifying unilateral prostate cancer. However, a 12‐core biopsy is not an ideal diagnostic test to select patients for focal therapy, and should be interpreted in conjunction with imaging and clinical variables. Additional research should investigate the diagnostic gain associated with a further increase in the number of biopsy cores.     

Underestimation of Gleason score at prostate biopsy reflects sampling error in lower volume tumours

Study Type – Diagnostic (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The Gleason score of prostate cancer is frequently underestimated at the time of diagnostic biopsy, although the contribution of sampling error to its incidence is unknown. We show that under‐graded tumours are significantly smaller that tumours concordant for the higher grade, indicating that incomplete tumour sampling plays a significant role in Gleason score assignment error.

OBJECTIVE

• ? To determine the influence of tumour and prostate gland volumes on the underestimation of prostate cancer Gleason score in diagnostic core biopsies.

PATIENTS AND METHODS

• ? Patients undergoing radical prostatectomy with matched diagnostic biopsies were identified from a prospectively recorded database.
• ? Tumour volumes were measured in serial whole‐mount sections with image analysis software as part of routine histological assessment.
• ? Differences in various metrics of tumour and prostate volume between upgraded tumours and tumours concordant for the lower or higher grade were analysed.

RESULTS

• ? In all, 684 consecutive patients with Gleason score 6 or 7 prostate cancer on diagnostic biopsy were identified.
• ? Of 298 patients diagnosed with Gleason 6 tumour on biopsy, 201 (67.4%) were upgraded to Gleason 7 or higher on final pathology. Similarly, of 262 patients diagnosed with Gleason 3 + 4 = 7 prostate cancer on initial biopsy, 60 (22.9%) were upgraded to Gleason score 4 + 3 = 7 or higher.
• ? Tumours upgraded from Gleason 6 to 7 had a significantly lower index tumour volume (1.73 vs 2 mL, P= 0.029), higher calculated prostate volume (41.6 vs 39 mL, P= 0.017) and lower relative percentage of tumour to benign glandular tissue (4.3% vs 5.9%, P= 0.001) than tumours concordant for the higher grade.
• ? Similarly, tumours that were Gleason score 3 + 4 on biopsy and upgraded on final pathology to 4 + 3 were significantly smaller as measured by both total tumour volume (2.3 vs 3.3 mL, P= 0.005) and index tumour volume (2.2 vs 3, P= 0.027) and occupied a smaller percentage of the gland volume (6.3% vs 8.9%, P= 0.017) compared with tumours concordant for the higher grade.
• ? On multivariate analysis, lower prostate weight (hazard ratio 0.97, 95% confidence interval 0.96–0.99, P < 0.001) and larger total tumour volume (hazard ratio 1.87, 95% confidence interval 1.4–2.6, P < 0.001) independently predicted an upgrade in Gleason score from 6 to 7. In tumours upgraded from biopsy Gleason 3 + 4, only higher index tumour volume (hazard ratio 3.1, 95% confidence interval 1.01–9.3, P= 0.048) was a significant predictor of upgrading on multivariate analysis.

CONCLUSIONS

• ? Under‐graded tumours are significantly smaller than tumours concordant for the higher grade, indicating that incomplete tumour sampling plays a significant role in Gleason score assignment error.
• ? Surrogate measures of tumour volume may predict those at greatest risk of Gleason score upgrade.

     

Update on transrectal ultrasound-guided needle biopsy of the prostate

Over the past decade, the sextant biopsy technique has emerged as the standard of care in the detection of prostate cancer. This technique is easy to learn and well tolerated by patients and has a major complication rate of <1%. However, limitations in cancer detection have been appreciated, particularly a false-negative rate approaching 25%. This high failure rate has led investigators to refine biopsy techniques to improve cancer detection. Intuitively, increasing the total number of cores should improve cancer detection. However, the optimal core number has yet to be defined. Confounding factors include variability of prostate size, tumor volume, and tumor location. Currently, a new standard is emerging prescribing a minimum of eight cores, of which at least three are directed at the lateral aspect of the peripheral zone. These additional biopsies appear to enhance cancer detection by about 15%. The improved yield is most pronounced among patients with a serum prostate specific antigen concentration between 4 and 10 ng/mL and larger gland volume (>50 cc). These additional biopsies may decrease the need for repeat biopsies. In the meantime, strategies are being developed for the optimal technique of repeat biopsies among patients with persistent clinical suspicion in the setting of a prior negative biopsy. Currently, recommendations include increasing the biopsy number to a minimum of 10 cores, including sampling of the lateral peripheral and transition zones.     

Clinical staging error in prostate cancer: localization and relevance of undetected tumour areas

OBJECTIVE

To describe the localization and to assess the clinical implications of areas of undetected prostate cancer in radical prostatectomy (RP) specimens, focusing on patients with unilaterally negative preoperative biopsy cores.

PATIENTS AND METHODS

The study included 149 of 559 consecutive patients (26.7%) who had RP for prostate cancer. Unilateral prostate cancer was diagnosed from prostate biopsies, taken by several physicians, but ≥ pT2c disease was present in the RP specimen. The prostate was dissected by standardized transversal cuts and tumour areas were mapped by one genitourinary pathologist. To estimate the tumour size and location, areas of prostate cancer were transferred to a digital grid database representing the prostate by 794 units.

RESULTS

The most frequent location of undetected prostate cancer was in the dorsalateral region and in the apex of the prostate. The mean tumour volume of the false‐negative lobe was significantly lower than contralaterally (18.9 vs 47.5 units, P < 0.001). In 36 of 149 patients (24.2%), the tumour volume on the negative biopsy side was equal or higher than on the positive biopsy side; in the final RP specimen, 60 patients (40.3%) had capsular involvement on the negative biopsy side.

CONCLUSION

Significantly many patients with newly diagnosed prostate cancer remain clinically understaged. The apical and dorsolateral region of the prostate are not adequately represented in current biopsy strategies. Undetected tumour areas are often clinically significant by size and capsular involvement, indicating a direct clinical implication when planning nerve‐sparing RP or focal therapy. Our results show a continuing need for optimized and standardized biopsy protocols.     

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.