Random biopsy: when, how many and where to take the cores?

PURPOSE: The optimal random prostate biopsy scheme (PBx) in the initial and repeated setting is still an issue of controversy. We performed an analysis of the recent literature about the prostate biopsy techniques. METHODS: We performed a clinical and critical literature review by searching MEDLINE database from January 2005 up to January 2014. Electronic searches were limited to the English language, and the keywords prostate cancer, prostate biopsy, transrectal ultrasound, transperineal prostate biopsy were used. RESULTS: Prostate biopsy strategy in initial setting. According to the literature and the major international guidelines, the recommended approach in initial setting is still the extended scheme (EPBx) (12 cores). However, there is now a growing evidence in the literature that (a) saturation PBx (>20 cores) (SPBx) might be indicated in patients with PSA <10 ng/ml or low PSA density or large prostate and (b) an individualized approach with more than 12 cores according to the clinical characteristics of the patients may optimize cancer detection in the single patient. Moreover, in the era of multi-parametric MRI (mpMRI), EPBx or SPBX may be substituted by mpMRI-targeted biopsies that have demonstrated superiority over systematic random biopsies for the detection of clinically significant disease and representation of disease burden, while deploying fewer cores. Prostate biopsy strategy in repeat setting. How and how many cores should be taken in the different scenarios in the repeated setting is still unclear. SPBx clearly improves cancer detection if clinical suspicion persists after previous biopsy with negative findings and is able to provide an accurate prediction of prostate tumour volume and grade. Nevertheless, international guidelines do not strongly recommended SPBx in all situations of repeated setting. In the active surveillance and in focal therapy protocols, the optimal schemes have to be defined. CONCLUSIONS: The course of PBx has changed significantly from sextant biopsies to systematic and from extended to SPBx schemes. The issue about the number and location of the cores is still a matter of debate both in initial and in repeat setting. At present, EPBx is sufficient in most of the cases to provide adequate diagnosis and prostate cancer characterization in the initial setting, while SPBx seems to be necessary in repeat setting. The PBx schemes are evolving also because the scenario in which a PBx is necessary is changing. Random prostate PBx do not represent the future, while imaging target biopsy are becoming more popular.

Prostate cancer detection rates in different biopsy schemes. Which cores for which patients?

PURPOSE: To determine whether the addition of four paramedian peripheral and four lateral peripheral cores improves the cancer detection rate (CDR) of the extended 10-core biopsy scheme and which patients benefit most from such additional samples. METHODS: One thousand and ninety-one consecutive patients scheduled for first ultrasound-guided transrectal prostate biopsy prospectively underwent a 18-core biopsy scheme, including the traditional sextant (6-core), 4 lateral peripheral (10-core), 4 paramedian peripheral (14-core) and additional 4 lateral peripheral cores (18-core). RESULTS: The CDR of the 6-, 10-, 14- and 18-core schemes was 33.1, 39.2, 41.6 and 41.8 %, respectively; the difference between the 10- and 6-core scheme reached significance (p < 0.005), whereas that between the 18- or 14- and the 10-core scheme did not. The percentage of tumors diagnosed on the sole basis of the 14-core scheme was significantly greater in patients with low PSA (≤ 7.2 vs. >7.2 ng/ml: 12.1 vs. 1.8 %; p < 0.0001), large prostate volume (≥ 50 vs. <50 cc: 3.4 vs. 9.1 %; p = 0.011) and particularly low PSA density (<0.15 vs. ≥ 0.15: 15.9 vs. 1 %; p < 0.0001). The 18-core scheme did not provide diagnostic advantages in any patients' population. CONCLUSIONS: The addition of 4 lateral peripheral samples did not increase the CDR of the 10-core biopsy scheme. The addition of four paramedian peripheral samples was beneficial only in patients with PSA density <0.15, in whom the 10-core scheme would have miss almost 16 % of tumors. Since more than half of our patients had low (<0.15) PSA density, these findings seem to be of great clinical relevance.

Repeated biopsy in the detection of prostate cancer: when and how many cores.

PURPOSE: We performed an analysis of the literature about the optimal prostate biopsy (PBX) scheme in the repeated setting METHODS: We performed a clinical and critical literature review by searching Medline Database from January 2005 up to January 2014. Electronic searches were limited to the English language. The keywords were: prostate cancer, prostate biopsy, transrectal ultrasound, transperineal prostate biopsy. RESULTS: The recommended approach in repeated setting is still the extended scheme (EPBx) (12 cores). An approach with more than 12 cores according to the clinical characteristics of the patients may optimize cancer detection. Saturation PBx (> 20 cores) clearly improves cancer detection if clinical suspicion persists after previous negative biopsy. Nevertheless international guidelines do not strongly recommended SPBx in all situations of repeated setting. EPBx or SPBX may be, in the future, substituted by multiparametric MRI-targeted biopsies. CONCLUSIONS: Since the scenario in which a PBx is changing, the issue about the number and location of the cores in PBx is still a matter of debate in repeated setting. At present, EPBx are still the gold standard even if SPBx seems to be necessary in many cases. However, random PBx does not represent the approach of the future, but rather imaging targeted biopsy.

Practical recommendations for performing ultrasound scanning in the urological and andrological fields.

AIM: US scanning has been defined as the urologist's stethoscope. These recommendations have been drawn up with the aim of ensuring minimum standards of excellence for ultrasound imaging in urological and andrological practice. A series of essential recommendations are made, to be followed during ultrasound investigations in kidney, prostate, bladder, scrotal and penile diseases. METHODS: Members of the Imaging Working Group of the Italian Society of Urology (SIU) in collaboration with the Italian Society of Ultrasound in Urology, Andrology and Nephrology (SIEUN) identified expert Urologists, Andrologists, Nephrologists and Radiologists. The recommendations are based on review of the literature, previously published recommendations, books and the opinions of the experts. The final document was reviewed by national experts, including members of the Italian Society of Radiology. RESULTS: Recommendations are listed in 5 chapters, focused on: kidney, bladder, prostate and seminal vesicles, scrotum and testis, penis, including penile echo-doppler. In each chapter clear definitions are made of: indications, technological standards of the devices, the method of performance of the investigation. The findings to be reported are described and discussed, and examples of final reports for each organ are included. In the tables, the ultrasound features of the principal male uro-genital diseases are summarized. Diagnostic accuracy and second level investigations are considered. CONCLUSIONS: Ultrasound is an integral part of the diagnosis and follow-up of diseases of the urinary system and male genitals in patients of all ages, in both the hospital and outpatient setting. These recommendations are dedicated to enhancing communication and evidence-based medicine in an inter- and multi-disciplinary approach. The ability to perform and interpret ultrasound imaging correctly has become an integral part of clinical practice in uro-andrology, but intra and inter-observer variability is a well known limitation. These recommendations will help to improve reliability and reproducibility in uro-andrological ultrasound scanning.

Head-to-head comparison of prostate health index and urinary PCA3 for predicting cancer at initial or repeat biopsy.

PURPOSE: We performed a head-to-head comparison of the PHI (Prostate Health Index) and PCA3. MATERIALS AND METHODS: We evaluated PHI and PCA3 performance in 211 patients undergoing initial (116) or repeat (95) prostate biopsy. Multivariable logistic regression analysis was done using the AUC to test the accuracy of PHI and PCA3 for predicting prostate cancer in the overall population and in each setting. Decision curve analysis was used to compare the clinical benefit of different models. RESULTS: Overall, the AUC of the PHI (0.70) was significantly higher than the AUC of PCA3 (0.59), total prostate specific antigen (0.56) and free-to-total prostate specific antigen (0.60) (p = 0.043, 0.002 and 0.037, respectively). PHI was more accurate than PCA3 for predicting prostate cancer in the initial setting (AUC 0.69 vs 0.57) and in the repeat setting (AUC 0.72 vs 0.63), although no statistically significant difference was observed. Including PCA3 in the base multivariable model (prostate specific antigen plus free-to-total prostate specific antigen plus prostate volume) did not increase predictive accuracy in either setting (AUC 0.79 vs 0.80 and 0.75 vs 0.76, respectively). Conversely, including PHI in the base multivariable model improved predictive accuracy by 5% (AUC 0.79 to 0.84) and 6% (AUC 0.75 to 0.81) in the initial and repeat prostate biopsy settings, respectively. On decision curve analysis the highest net benefit was observed when PHI was added to the base multivariable model. CONCLUSIONS: PHI and PCA3 provide a significant increase in sensitivity and specificity compared to all other examined markers and they may help guide biopsy decisions. PCA3 does not increase the accuracy of predicting prostate cancer when PHI is assessed.

The number of cores taken in patients diagnosed with a single microfocus at initial biopsy is a major predictor of insignificant prostate cancer.

PURPOSE: Patients with a single microfocus of prostate cancer at initial biopsy represent the ideal candidates for active surveillance. We investigate whether the number of cores taken affects the concordance rate between microfocus of prostate cancer and the confirmation of a pathologically insignificant prostate cancer at radical prostatectomy. MATERIALS AND METHODS: Data were analyzed from 233 patients with a single microfocus of prostate cancer at initial transrectal prostate biopsy (a single focus of Gleason 6 involving 5% or less of the core) subsequently treated with radical prostatectomy. The chi-square test, cubic spline analyses and logistic regression analyses were used to depict the relationship between the number of cores taken and the probability of confirming the presence of an indolent disease (pathologically confirmed insignificant prostate cancer defined as radical prostatectomy Gleason score 6 or less, tumor volume 0.5 ml or less and organ confined disease). RESULTS: Overall 65 patients (27.9%) showed pathologically confirmed insignificant prostate cancer at radical prostatectomy. The rate of pathologically confirmed insignificant prostate cancer was 3.8%, 29.6% and 39.4% in patients who underwent biopsy of 12 or fewer cores, 13 to 18 cores and 19 or more cores, respectively (p <0.001). After adjusting for the available confounders, age (p = 0.04), number of cores taken (p <0.001) and prostate specific antigen density (p <0.02) were independent predictors of pathologically confirmed insignificant prostate cancer. CONCLUSIONS: Of patients diagnosed with a single microfocus of prostate cancer the number of biopsy cores taken was a major independent predictor of having pathologically confirmed insignificant prostate cancer at radical prostatectomy. Therefore, when active surveillance is considered as a possible alternative in patients with microfocus of prostate cancer, the number of cores taken should be taken into account in decision making.

Impact of the introduction of a robotic training programme on prostate cancer stage migration at a single tertiary referral centre.

OBJECTIVE: To evaluate the trend in robot-assisted radical prostatectomy (RARP) and open retropubic radical prostatectomy (RRP) use over time and to compare preoperative and pathological characteristics of patients treated with RARP or RRP at a single centre. PATIENTS AND METHODS: Between 2006 and 2010, 2511 consecutive patients treated with RP, with or without pelvic lymph node dissection (PLND), for prostate cancer (PCa) at a single tertiary care centre were analysed. Baseline patient characteristics and PCa risk distribution were compared according to treatment type (RRP vs RARP) in the overall population, as well as in three surgeons' initial 50 RARP and three surgeons' initial 50 RRP cases (n = 300). We used a chi-squared trend test to evaluate the differences in treatment type administration over time according to PCa characteristics. Logistic regression analyses focused on the prediction of PLND and adjuvant radiotherapy (RT) use. RESULTS: Overall, 1873 (74.6%) and 638 (25.4%) patients underwent RRP and RARP, respectively. Men treated with RARP were younger (mean age: 62 vs 65 years), less obese (mean BMI: 24.8 vs 26.4 kg/m(2) ), healthier (Charlson comorbidity index = 0: 68.7 vs 53.3%) and more likely to harbour clinical low-risk PCa (51 vs 30%) than their RRP counterparts (all P < 0.001). Similar findings were observed in sub-analyses focusing on six surgeons' 50 initial patients (all P ≤ 0.02). A significant increase in the rate of patients with low-risk PCa treated with RARP vs RRP was reported over time (5 vs 95% and 66 vs 34% in 2006 and 2010, respectively). Conversely, 76% of patients with high risk PCa were still treated with RRP in 2010. Patients treated with RARP were less likely to receive PLND at RP and adjuvant RT (all P ≤ 0.01), even after adjusting for clinical and PCa characteristics. CONCLUSIONS: The introduction of a robotic training programme at a high volume centre led to significant patient selection in terms of clinical and PCa characteristics. When both RRP and RARP facilities are available within the same centre, patients with the most favourable clinical and cancer profile are selected to undergo RARP. Use of RARP negatively influenced the rates and the extent of PLND as well as the use of adjuvant RT after surgery. Thus, baseline patient selection, surgical and treatment biases make any comparisons of RARP with RRP problematic.

Spatial distribution of positive cores improves the selection of patients with low-risk prostate cancer as candidates for active surveillance.

OBJECTIVE: To test the hypothesis that spatial distribution of positive cores at biopsy is a predictor of unfavourable prostate cancer characteristics at radical prostatectomy (RP) in active surveillance (AS) candidates. PATIENTS AND METHODS: We examined the data of 524 patients treated with RP, between 2000 and 2012. All fulfilled at least one of four commonly used AS criteria. Regression models tested the relationship between positive cores spatial distribution, defined as the number of positive zones at biopsy (PBxZ) and tumour laterality at biopsy and two endpoints: (i) unfavourable prostate cancer at RP (Gleason score ≥ 4 + 3, and/or pT3 disease), and (ii) clinically significant prostate cancer (tumour volume ≥ 2.5 mL). RESULTS: Unfavourable prostate cancer and clinically significant prostate cancer rates were 8 and 25%, respectively. Patients with more than one PBxZ had a 3.2-fold higher risk of harbouring unfavourable prostate cancer, and a 2.3-fold higher risk of harbouring clinically significant prostate cancer compared with their counterparts with one PBxZ (both P = 0.01). Patients with bilateral tumour at biopsy had a 3.3-fold higher risk of harbouring unfavourable prostate cancer and a 1.7-fold higher risk of harbouring clinically significant prostate cancer compared with their counterparts with unilateral tumour at biopsy (both P ≤ 0.04). Some of these results did not reach a statistically significant level, when the analyses were restricted to patients that fulfilled the most stringent AS criteria. CONCLUSIONS: Positive cores spatial distribution at biopsy should be considered, when advising patients about AS. The addition of this predictor to AS inclusion criteria can help identifying patients at a higher risk of progression, and reduce the rate of inappropriate surveillance of aggressive tumours. However, the most stringent AS criteria (namely John-Hopkins criteria and Prostate Cancer Research International: Active Surveillance criteria) might not benefit from the addition of this predictor. This point warrants further investigation in future studies.

Ureteral endometriosis: proposal for a diagnostic and therapeutic algorithm with a review of the literature.

INTRODUCTION: The ureteral involvement in deep pelvic endometriosis in usually asymptomatic and might lead to a silent loss of renal function. As a matter of fact, the diagnosis and the treatment modalities are still a matter of debate. MATERIALS AND METHODS: We performed a literature review by searching the MEDLINE database for articles published in English between 1996 and 2010, using the key words urinary tract endometriosis, ureteral endometriosis, diagnosis and treatment. We found more than 200 cases of ureteral endometriosis (UE). RESULTS: The disease most commonly affects a single distal segment of the ureter, with a left predisposition in most of the patients. Two major pathological types of UE may be distinguished: intrinsic and extrinsic. The symptoms are usually nonspecific and owing to secondary obstruction. The diagnosis has to be considered as a step- by-step procedure, starting from physical examination to highly detailed imaging methods. Nowadays, the treatment is usually chosen according to the type of UE, the site lesion and the distance to the ureteral orifice, with the use of JJ stents remaining a matter of debate. CONCLUSIONS: A close collaboration between the gynecologist and the urologist is advisable, especially in referral centers. Surgical treatment can lead to good results in terms of both patient compliance and prognosis.

Impact of Early Dorsal Venous Complex Ligation on Urinary Continence Recovery after Robot-assisted Radical Prostatectomy: Results from a Phase 3 Randomized Controlled Trial.

BACKGROUND: Whether early ligation of the dorsal venous complex (DVC) might improve recovery of urinary continence (UC) after robot-assisted radical prostatectomy (RARP) has never been investigated in a prospective randomized study. OBJECTIVE: To assess whether early DVC ligation might affect UC recovery after RARP. INTERVENTION: DVC ligation (early vs standard). DESIGN, SETTING, AND PARTICIPANTS: A total of 312 patients with prostate cancer underwent primary RARP at a tertiary care institution. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was UC recovery at 1 and 4 mo after RARP. UC was defined as 0 pads/1 safety pad per day. All patients completed the International Prostate Symptom Score (IPSS) and International Consultation of Incontinence Questionnaire (ICIQ)-Short Form questionnaires. Secondary outcomes were early (≤4 mo) erectile function recovery, the positive surgical margin (PSM) rate, 30-d Clavien-Dindo complications, and biochemical recurrence rates. Quality of life was assessed using the EQ-5D-5L questionnaire. The association between treatment arm and UC recovery was also tested using multivariable regression models. RESULTS AND LIMITATIONS: After surgery, 23 patients withdrew their consent and 29 were lost to follow-up, leaving 261 patients available for per-protocol analyses. Of these, 32 patients (24%) in the experimental group and 37 (29%) in the control group used no pad/one safety pad at 1 mo after RARP, whereas 96 (72%) in the control group versus 83 (65%) in the control group were continent at 4-mo follow-up (both p = 0.3). Median ICIQ and IPSS scores did not differ between the groups at both time points. The results were confirmed on multivariable regression analyses. PSMs were observed for 32 patients (25%) in the experimental group versus 30 (22%) in the control group (p = 0.6). The incidence of postoperative complications (17% experimental vs 13% control) and the 1-yr biochemical recurrence-free survival did not differ between the groups. CONCLUSIONS: In this randomized clinical trial, we did not find evidence that early ligation of the DVC during RARP was associated with better UC recovery after surgery in comparison to the standard technique. Given its safety in terms of surgical margins and complications, this technique may be considered as an option for surgical dissection according to the physician's preference. PATIENT SUMMARY: Our trial showed that for patients undergoing robot-assisted surgical removal of the prostate, the timing of a specific step to control bleeding from a network of veins draining the prostate did not affect recovery of urinary continence after surgery. The results indicate that earlier control of these veins may be considered as an option according to the surgeon's preference.

Holmium Laser Enucleation of the Prostate Is Associated with Complications and Sequelae Even in the Hands of an Experienced Surgeon Following Completion of the Learning Curve.

BACKGROUND: Holmium laser enucleation of the prostate (HoLEP) is considered a challenging procedure even for surgeons who have completed the learning curve. OBJECTIVES: To assess outcomes and complications following HoLEP performed by a highly experienced surgeon. DESIGN, SETTING, AND PARTICIPANTS: This was a single-institution prospective study (NCT03583034) performed at a tertiary referral centre that included 243 consecutive patients with lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE) treated with HoLEP by a single experienced surgeon (>1600 cases). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients were assessed using validated questionnaires and uroflowmetry at baseline and several follow-up dates. Intraoperative and postoperative complications were recorded. Kaplan-Meier analysis was used to estimate recovery rates for urinary continence and erectile function. Logistic regression models were constructed to assess predictors of postoperative complications. RESULTS AND LIMITATIONS: Of the 243 patients, 78 (32.1%) had an indwelling urethral catheter. The median prostate volume (PV) was 87 cm3 (interquartile range 60-115) and 146 patients (59.8%) had PV >80 cm3. At 3-mo follow-up, 219 patients (90.1%) had a peak flow rate >20 ml/s and 182 (74.9%) had no postvoid residual urine. The improvement in subjective symptoms was significant at 1-mo follow-up and was maintained until 12 mo after surgery. Urinary continence recovery was slow, with an estimated rate of 68% (95% confidence interval [CI] 62-74%) at 1 mo and 94% (95% CI 91-97%) at 12 mo after HoLEP. The recovery rate for erectile function was 53% (95% CI 46-61%) at 1 mo and 85% (95% CI 77-90%) at 12 mo. Postoperative complications occurred in 36 patients (14.8%) during their hospital stay, in 34 (14%) within 1 mo following discharge from hospital, and in ten (4.1%) at later follow-up dates. Clinically significant complications (Clavien-Dindo ≥2) were observed in 44 cases (18%) and were more common for patients with an indwelling catheter at baseline (odds ratio 5.05; p = 0.006). CONCLUSIONS: HoLEP is an effective procedure for treating LUTS due to BPE, although it is not devoid of complications and sequelae, even in the hands of a highly experienced surgeon. PATIENT SUMMARY: Holmium laser treatment of the prostate to reduce its size has positive results for urinary function when performed by an experienced surgeon, even in complex cases, although there can be complications.

Development and internal validation of a Prostate Health Index based nomogram for predicting prostate cancer at extended biopsy.

PURPOSE: We developed and validated a Prostate Health Index (Beckman Coulter, Brea, California) based nomogram to predict prostate cancer at extended prostate biopsy. MATERIALS AND METHODS: The study population consisted of 729 patients who were scheduled for prostate biopsy following suspicious digital rectal examination and/or increased prostate specific antigen. Total and free prostate specific antigen, percent free-to-total prostate specific antigen, [-2]proPSA and the prostate health index [([-2]proPSA/free prostate specific antigen) × âˆštotal prostate specific antigen)] were determined. Logistic regression models were fitted to test prostate cancer predictors. Predictive accuracy estimates of biopsy outcome predictions were quantified. Regression coefficients were used to create a decision making tool to predict prostate cancer. A calibration plot was used to evaluate the extent of overestimating or underestimating the observed prostate cancer rate. Decision curve analysis provided an estimate of the net benefit obtained using the prostate health index based nomogram. RESULTS: Overall 280 of 729 patients (38.4%) were diagnosed with prostate cancer at extended prostate biopsy. On accuracy analyses prostate health index emerged as the most informative predictor of prostate cancer (AUC 0.70) compared to established predictors, such as total prostate specific antigen (0.51) and percent free-to-total prostate specific antigen (0.62). Including the prostate health index in a multivariable logistic regression model based on patient age, prostate volume, digital rectal examination and biopsy history significantly increased predictive accuracy by 7% from 0.73 to 0.80 (p <0.001). Nomogram calibration was good. Decision curve analysis showed that using the prostate health index based nomogram resulted in the highest net benefit. CONCLUSIONS: The prostate health index based nomogram can assist clinicians in the decision to perform biopsy by providing an accurate estimation of an individual risk of prostate cancer.

Serum index test %[-2]proPSA and Prostate Health Index are more accurate than prostate specific antigen and %fPSA in predicting a positive repeat prostate biopsy.

PURPOSE: We tested the hypothesis that serum isoform [-2]proPSA derivatives %p2PSA and Prostate Health Index are accurate predictors of prostate cancer in men scheduled for repeat biopsy. MATERIALS AND METHODS: The study was an observational prospective evaluation of a clinical cohort of men with 1 or 2 previous negative prostate biopsies, with persistent suspicion of prostate cancer. They were enrolled in the study to determine the diagnostic accuracy of %p2PSA using the formula, (p2PSA pg/ml)/(free prostate specific antigen ng/ml × 1,000)]× 100, and Beckman-Coulter Prostate Health Index using the formula, (p2PSA/free prostate specific antigen) × âˆštotal prostate specific antigen), and to compare it with the accuracy of established prostate cancer serum tests (total prostate specific antigen, free prostate specific antigen and percent free prostate specific antigen). Multivariable logistic regression models were complemented by predictive accuracy analysis and decision curve analysis. RESULTS: Prostate cancer was found in 71 of 222 (31.9%) subjects. %p2PSA and Prostate Health Index were the most accurate predictors of disease. %p2PSA significantly outperformed total prostate specific antigen, free prostate specific antigen, percent free prostate specific antigen and p2PSA in the prediction of prostate cancer (p ≤0.01), but not Prostate Health Index (p = 0.094). Prostate Health Index significantly outperformed total prostate specific antigen and p2PSA (p ≤0.001) but not free prostate specific antigen (p = 0.109) and free/total prostate specific antigen (p = 0.136). In multivariable logistic regression models %p2PSA and Prostate Health Index achieved independent predictor status, and significantly increased the accuracy of multivariable models including prostate specific antigen and prostate volume with or without percent free prostate specific antigen and prostate specific antigen density by 8% to 11% (p ≤0.034). At a %p2PSA cutoff of 1.23, 153 (68.9%) biopsies could have been avoided, missing prostate cancer in 6 patients. At a Prostate Health Index cutoff of 28.8, 116 (52.25%) biopsies could have been avoided, missing prostate cancer in 6 patients. CONCLUSIONS: Serum %p2PSA and Prostate Health Index are more accurate than standard reference tests in predicting repeat prostate biopsy outcome, and could avoid unnecessary repeat biopsies.

Unilateral positive biopsies in low risk prostate cancer patients diagnosed with extended transrectal ultrasound-guided biopsy schemes do not predict unilateral prostate cancer at radical prostatectomy.

UNLABELLED: Focal therapy is an emergent therapeutic option for prostate cancer. Focal therapy includes a variety of therapeutic approaches ranging from lesion treatment to sub-total gland treatment. In this context, an accurate selection of patients having unilateral prostate cancer is closely related to the success of these strategies, especially when a hemi-ablative approach is considered. As prostate cancer is often multifocal, the critical issue is whether it is possible to preoperatively predict a clinically significant unifocal and/or unilateral lesion with sufficient accuracy to recommend focal or hemi-ablative therapy, relying on clinical characteristics and pathological data derived from the biopsy. Our study clearly demonstrates that the prediction of unilateral prostate cancer is not accurate, based on preoperative variables (predictive accuracy 52.3%). Our study is the first study based on an extended biopsy template. Even in patients diagnosed with extended biopsy, the accuracy of the available predictors is far from the ideal prediction. To date, there is no way of correctly identifying patients who will harbour unilateral prostate cancer based on routinely available variables. OBJECTIVE: o establish the predictors of unilateral prostate cancer in a population of patients with low risk prostate cancer, diagnosed with extended biopsy and submitted to radical prostatectomy, potentially candidates for focal therapy. PATIENTS AND METHODS: The study included 321 consecutive patients with low risk (clinical stage T1, Gleason score 3 + 3 or less, prostate-specific antigen [PSA] < 10 ng/mL) unilateral prostate cancer diagnosed after extended biopsy who were subsequently treated with radical prostatectomy between 2002 and 2009 at a single institution. We evaluated the rate of unilateral prostate cancers at final pathology following radical prostatectomy, defined as pT2a or pT2b stage. Univariable and multivariable logistic regression analyses were used to identify predictors of unilateral prostate cancers. Predictive accuracy was assessed with estimates of the area under the receiver operating characteristic curve, which were subjected to 200 bootstraps to reduce overfit bias. RESULTS: At final pathology only 29.3% patients harboured unilateral prostate cancer. No significant differences in terms of age, preoperative PSA, prostate volume and percentage of positive cores were recorded between patients with unilateral prostate cancer and patients with more advanced stage (all P ≥ 0.07). Patients harbouring unilateral prostate cancer had a smaller number of positive biopsy cores (2.8 vs 3.2, P = 0.056) compared with patients with stage pT2c or higher at final pathology. Patients with unilateral prostate cancer had a higher rate of Gleason sum 6 compared with patients with more advanced pathological stage (pT2c or higher: 85.1% vs 65.6%; P = 0.002). On multivariable analyses, only the percentage of positive cores (odds ratio 0.57; P = 0.047) was an independent predictor of unilateral prostate cancer at radical prostatectomy, after controlling for age, PSA at diagnosis and prostate volume (all P ≥ 0.3). The newly developed model for identifying the presence of unilateral prostate cancer failed to achieve accurate prediction (area under the curve 52.3%). When only patients with a single positive core were considered, no differences in PSA and prostate volume were detected (all P ≥ 0.5) and a similar rate of unilateral prostate cancer was demonstrated (33.3% vs 28.4%; P = 0.5). CONCLUSIONS: In patients with unilateral low risk prostate cancer at biopsy, only one-third showed unilateral prostate cancer at radical prostatectomy. The number of cores and the number of positive cores represented independent predictors of unilateral prostate cancer. However, the accuracy of the multivariable model in predicting unilateral prostate cancer is low (52.3%), thus making prediction of unilateral prostate cancer extremely inaccurate. These results need to be taken into account in those cases where focal therapy is considered as a treatment of prostate cancer.

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

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.

Diagnosis of isolated high-grade prostatic intra-epithelial neoplasia: proposal of a nomogram for the prediction of cancer detection at saturation re-biopsy.

UNLABELLED: Study Type--Diagnostic (case series). Level of Evidence 4. What's known on the subject? And what does the study add? Multifocality, age, PSA values, and biopsy protocols regarding the predictive value of high grade PIN have been discussed extensively in the literature. Our study developed for the first time a predictive nomogram that could be helpful for patient counselling and to guide the urologist to perform rPBX after an initial diagnosis of isolated HGPIN. OBJECTIVE: • To evaluate factors that may predict prostate cancer (PCa) detection after the initial diagnosis of high-grade prostatic intra-epithelial neoplasia (HGPIN) on prostate biopsy (PBx) with six to 24 random cores. PATIENTS AND METHODS: • We retrospectively evaluated 262 patients submitted from 1998 to 2007 to prostate re-biopsy (rPBx) after an initial HGPIN diagnosis in tertiary academic centres. • HGPIN diagnosis was obtained on initial systematic PBx with six to 24 random cores. • All patients were re-biopsied with a 'saturation' rPBx with 20-26 cores, with a median time to rPBx of 12 months. • All slides were reviewed by expert uropathologists. RESULTS: • Plurifocal HGPIN (pHGPIN) was found in 115 patients and monofocal HGPIN (mHGPIN) was found in 147 patients. • In total, 108 and 154 patients, respectively, were submitted to >12-core initial PBx and ≤12-core initial PBx. • Overall PCa detection at rPBx was 31.7%. PSA level (7.7 vs 6.6 ng/mL; P= 0.031) and age (68 vs 64 years; P= 0.001) were significantly higher in patients with PCa at rPBx. • PCa detection was significantly higher in patients with a ≤12-core initial PBx than in those with a >12-core initial PBx (37.6% vs 23.1%; P= 0.01), as well as in patients with pHGPIN than in those with mHGPIN (40% vs 25.1%; P= 0.013). • At multivariable analysis, PSA level (P= 0.041; hazards ratio, HR, 1.08), age (P < 0.001; HR, 1.09), pHGPIN (P= 0.031; HR, 1.97) and ≤12-core initial PBx (P= 0.012; HR, 1.95) were independent predictors of PCa detection. • A nomogram including these four variables achieved 72% accuracy for predicting PCa detection after an initial HGPIN diagnosis. CONCLUSIONS: • PCa detection on saturation rPBx after an initial diagnosis of HGPIN is significantly higher in patients with a ≤12-core initial PBx than those with a >12-core initial PBx and in patients with pHGPIN than in those with mHGPIN. • We developed a simple prognostic tool for the prediction of PCa detection in patients with initial HGPIN diagnosis who were undergoing saturation rPBx.

Diagnosis and treatment of bladder endometriosis: state of the art.

BACKGROUND: The bladder is the most common affected site in urinary tract endometriosis, being diagnosed during gynecologic follow-up. The surgical urological treatment might lead to good results. STUDY OBJECTIVE: To define the state of the art in the diagnosis and treatment of bladder endometriosis. METHODS: We performed a literature review by searching the MEDLINE database for articles published between 1996 and 2011, limiting the searches to the words: urinary tract endometriosis, bladderendometriosis, symptoms, diagnosis and treatment. RESULTS: Deep pelvic endometriosis usually involves the urinary system, with the bladder being affected in 85% of cases. The diagnosis has to be considered as a step-by-step procedure. Currently, the treatment is usually surgical, consisting of either transurethral resection or partial cystectomy, and eventually associated with hormonal therapy. The hormonal therapy alone counteracts only the stimulus of endometriotic tissue proliferation, with no effects on the scarring caused by this tissue. The overall recurrence rate is about 30% for combined therapies and about 35% for the hormonal treatment alone. CONCLUSIONS: The bladder is the most common affected site in urinary tract endometriosis. Most of the time, this condition is diagnosed because of the complaint of urinary symptoms during gynecologic follow-up procedures for a deep pelvic endometriosis: a close collaboration between the gynecologist and the urologist is advisable, especially in highly specialized centers. The surgical urological treatment might lead to good results in terms of patients' compliance and prognosis.

Prostate saturation biopsy following a first negative biopsy: state of the art.

INTRODUCTION: Saturation prostate biopsy (SPBx) has been initially introduced to improve prostate cancer (PCa) detection rate (DR) in the repeat setting. Nevertheless, the optimal number and the most appropriate location of the cores, together with the timing to perform a second PBx and the eventual modification of the PBx protocols according to the different clinical situations, are matters of debate. The aim of this review is to perform a critical analysis of the literature about the actual role of SPBx in the repeat setting. MATERIALS AND METHODS: We performed a systematic review of the literature since 1995 up to 2011. Electronic searches were limited to the English language, using the MEDLINE database. The key words 'saturation prostate biopsy' and 'repeated prostate biopsy' were used. RESULTS: SPBx improves PCa DR if clinical suspicion persists after previous biopsy with negative findings and provides an accurate prediction of prostate tumor volume and grade, even if the issue about the number and locations of the cores is still a matter of debate. CONCLUSIONS: At present, SPBx seems to be really necessary in men with persistent suspicion of PCa after negative initial biopsy and probably in patients with a multifocal high-grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. In the remaining situations, adopting an individualized scheme is preferable.

Observational database serenoa repens (DOSSER): overview, analysis and results. A multicentric SIUrO (Italian Society of Oncological Urology) project.

OBJECTIVE: Men affected with Benign Prostate Hyperplasia (BPH) and Lower Urinary Tract Symptoms (LUTS) are demonstrating to require an increasing amount of attention from Urologists and Primary-care Physicians. Over the years, common urological medications were based on either alpha-blockers and/or 5alpha-reductase inhibitors. During the last decade the phytotherapeutic drugs are gaining a more often central role in the BPH and LUTS managements. In particular, clinical usage of the extract of the dried ripe fruit of serenoa repens with a dosage of 320 mg per day, has shown its clinical efficacy and its superiority. Purpose of this multicentric observational retrospective study was to evaluate all the urological aspects (clinical, biochemical, instrumental and pathological) of patients affected by BPH and LUTS, with a PSA < 10 ng/ml, a previous negative prostatic biopsy and in therapy with a daily dose of 320/640 mg of serenoa repens. PATIENTS AND METHODS: The study was conducted in 8 different centers throughout Italy from September 2010 to November 2011. Data and information of 298 men with an average of 63 years (mean PSA of 5.4 ng/ml and mean prostate gland volume of 57 cc), affected by non-acute urinary symptoms caused by BPH, a dosed PSA level inferior to 10 ng/ml, a previous negative prostate biopsy and in therapy with serenoa repens alone or associated to an alpha-blocker, were retrospectively inserted in an extensive on-line SIUrO Database. Comprehensive questionnaires were filled in for each patient at 3 and 6 months of follow-up. Each questionnaire contained various sections, each of them composed by several items: dosed PSA levels, uroflowmetry, International Prostate Symptoms Score (IPSS), International Index of Erectile Function (IIEF-5), trans-rectal ultrasound (TRUS) patterns, digital rectal examinations (DRE) aspects, previous prostate bioptical results (histology) and side effects. RESULTS: PSA levels weren't subjected to an increase, revealing a stabilizing or downward trend. Percentage of patients with PSA below the level of 4 ng/mL was lower at the end of the study. The overall changes in the uroflowmetry were similar and parallel both in the group with only serenoa repens intake and in the group with serenoa repens plus alpha-blocker. The mean medium flow and the mean maximum flow had a slightly increase along the observation time. There was a substantial decreasing in the amount of patients presenting severe prostatic symptoms. Patients reported through the IIEF-5 score a sexual activity substantially unchanged after 6 months of follow-up. The serenoa repens intake resulted in an improvement of the "inflammatory-like reports", in terms of ultrasound patterns, DRE and bioptical features. CONCLUSIONS: serenoa repens demonstrated its efficacy reducing dysuria with minimal side effects. Further prospective studies might confirm its stabilization or lowering role on PSA levels in this cohort of patients and its possible clinical anti-inflammatory action.