Vincenzo Scattoni

Systematic Review of Complications of Prostate Biopsy

CONTEXT Prostate biopsy is commonly performed for cancer detection and management. The benefits and risks of prostate biopsy are germane to ongoing debates about prostate cancer screening and treatment. OBJECTIVE To perform a systematic review of complications from prostate biopsy. EVIDENCE ACQUISITION A literature search was performed using PubMed and Embase, supplemented with additional references. Articles were reviewed for data on the following complications: hematuria, rectal bleeding, hematospermia, infection, pain, lower urinary tract symptoms (LUTS), urinary retention, erectile dysfunction, and mortality. EVIDENCE SYNTHESIS After biopsy, hematuria and hematospermia are common but typically mild and self-limiting. Severe rectal bleeding is uncommon. Despite antimicrobial prophylaxis, infectious complications are increasing over time and are the most common reason for hospitalization after biopsy. Pain may occur at several stages of prostate biopsy and can be mitigated by anesthetic agents and anxiety-reduction techniques. Up to 25% of men have transient LUTS after biopsy, and <2% have frank urinary retention, with slightly higher rates reported after transperineal template biopsy. Biopsy-related mortality is rare. CONCLUSIONS Preparation for biopsy should include antimicrobial prophylaxis and pain management. Prostate biopsy is frequently associated with minor bleeding and urinary symptoms that usually do not require intervention. Infectious complications can be serious, requiring prompt management and continued work into preventative strategies.

11C-Choline Positron Emission Tomography/Computerized Tomography for Preoperative Lymph-Node Staging in Intermediate-Risk and High-Risk Prostate Cancer: Comparison with Clinical Staging Nomograms

BACKGROUND Conventional imaging (CI) techniques are inadequate for lymph node (LN) staging in prostate cancer (PCa). OBJECTIVES To assess the accuracy of (11)C-Choline positron emission tomography/computerized tomography (PET/CT) for LN staging in intermediate-risk and high-risk PCa and to compare it with two currently used nomograms. DESIGN, SETTING, AND PARTICIPANTS From January 2007 to September 2007, 57 PCa patients at intermediate risk (n=27) or high risk (n=30) were enrolled at two academic centres. All patients underwent preoperative PET/CT and radical prostatectomy with extended pelvic LN dissection (PLND). Risk of LN metastasis (LNM) was assessed using available nomograms. MEASUREMENTS Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and number of correctly recognized cases for LNM detection at PET/CT were assessed. The accuracy of PET/CT for LNM detection was compared with the accuracy of nomograms for LNM prediction by using receiver operating characteristic (ROC) analysis. RESULTS AND LIMITATIONS Fifteen patients (26%) had LNMs, and a total of 41 LNMs were identified. On a patient analysis, sensitivity, specificity, PPV, NPV, and number of correctly recognized cases at PET/CT were 60.0%, 97.6%, 90.0%, 87.2%, and 87.7% while, on node analysis, these numbers were 41.4%, 99.8%, 94.4%, 97.2%, and 97.1%. The mean diameter (in mm) of the metastatic deposit of true-positive LNs was significantly higher than that of false-negative LNs (9.2 vs 4.2; p=0.001). PET/CT showed higher specificity and accuracy than the nomograms; however, in pairwise comparison, the areas under the curve (AUCs) were not statistically different (all p values >0.05). CONCLUSIONS In patients with intermediate-risk and high-risk PCa, (11)C-Choline PET/CT has quite a low sensitivity for LNM detection but performed better than clinical nomograms, with equal sensitivity and better specificity.

Pelvic/Retroperitoneal Salvage Lymph Node Dissection for Patients Treated With Radical Prostatectomy With Biochemical Recurrence and Nodal Recurrence Detected by [11C]Choline Positron Emission Tomography/Computed Tomography

BACKGROUND The management of patients with clinical recurrence of prostate cancer after radical prostatectomy (RP) remains challenging. OBJECTIVE To determine whether the removal of positive lymph nodes at [11C]choline positron emission tomography/computed tomography (PET/CT) scan may have an impact on the prognosis of patients with biochemical recurrence (BCR) and nodal recurrence after RP. DESIGN, SETTING, AND PARTICIPANTS Prospective analysis of 72 patients affected by BCR after RP associated with a nodal pathologic [11C]choline PET/CT scan. INTERVENTION Patients underwent salvage lymph node dissection (LND). MEASUREMENTS Biochemical response (BR) to treatment was defined as prostate-specific antigen (PSA) <0.2 ng/ml at 40 d after salvage LND. Kaplan-Meier and Cox regression analyses addressed time to and predictors of clinical recurrence (CR) after salvage LND, respectively. RESULTS AND LIMITATIONS Overall, 56.9% of patients achieved BR. Mean and median follow-up after LND were 39.4 and 39.8 mo, respectively. The 5-yr BCR-free survival rate was 19%. Preoperative PSA <4 ng/ml (hazard ratio [HR]: 0.12; p = 0.005), time to BCR <24 mo (HR: 7.52; p = 0.005), and negative lymph nodes at previous RP (HR: 0.19; p=0.04) represented independent predictors of BR. Overall, 5-yr CR-free and cancer-specific survival were 34% and 75%, respectively. At multivariable analyses, only PSA >4 ng/ml (HR: 2.13; p=0.03) and the presence of retroperitoneal uptake at PET/CT scan (HR=2.92; p=0.004) represented independent preoperative predictors of CR. Similarly, the presence of pathologic nodes in the retroperitoneum (HR: 2.78; p=0.02), higher number of positive lymph nodes (HR: 1.04; p=0.006), and complete BR to salvage LND (HR: 0.31; p=0.002) represented postoperative independent predictors of CR. Main limitations consisted of the lack of a control group and the heterogeneity of patients included in the analyses. CONCLUSIONS Salvage LND is feasible in patients with BCR after RP and nodal pathologic uptake at [11C]choline PET/CT scan. Biochemical response after surgery can be achieved in a consistent proportion of patients. Although most patients invariably progressed to BCR after surgery at longer follow-up, 35% of patients showed the absence of CR at 5 yr.

Contemporary Role of Systematic Prostate Biopsies: Indications, Techniques, and Implications for Patient Care

CONTEXT Prostate cancer (PCa) screening to detect early stage PCa has resulted in increased identification of small-volume, low-grade PCa, many of which meet criteria for clinically indolent disease. Nevertheless, there remains some degree of underdetection of high-risk PCa in substantial numbers of men despite current diagnostic strategies. OBJECTIVE To discuss the contemporary role of prostate biopsy (PB), focusing on the indications, techniques, and limitations of current PB techniques and evolving techniques affecting patient care. EVIDENCE ACQUISITION A comprehensive Medline search was performed using the medical subject heading search terms prostate cancer, detection, prostate biopsy, significant cancer, and diagnosis, with restriction to the English language. Emphasis was given to publications within the past 5 yr. EVIDENCE SYNTHESIS Because abnormal digital rectal examination (DRE) and prostate-specific antigen (PSA) tests alone lack specificity for cancer, there is no universal indication for PB. This lack has inspired exploration for a cancer-specific biomarker and prediction tools such as risk calculators. Indication for biopsy should involve a balance between the underdiagnosis of high-risk cancers and the potential risks for the overdetection of clinically insignificant cancers as well as biopsy-related morbidity. Evidence supports the inclusion of laterally directed cores during transrectal ultrasound (TRUS) PB in addition to the traditional sextant pattern, which significantly improves cancer detection without a demonstrable increase in morbidity. These data indicate that such PB templates, typically 12 cores, represent the optimal template in initial PB. Optimised techniques and templates for repeat PB remain controversial. However, debate continues regarding indications, sampling number, and location as well as on the potential of modern image-guided approaches or three-dimensional (3D) mapping biopsy in this unique setting. Additional limitations of repeat PB techniques include associated procedural risks if general anaesthesia is required and inherent sampling errors of template-based techniques that are not targeted to the specific tumour site. CONCLUSIONS Current data support the utility of extended PB templates for initial TRUS PB intended to detect clinically significant PCa. Repeat PB in the setting of prior negative PB on the grounds of clinical suspicion or for risk-stratified approaches to management of low risk PCa requires balancing overdetection of low-risk cancer with the potential to miss significant cancer. Several options, including modern image-guided targeting, biomarker development, transrectal saturation PB, and 3D template mapping PB, are changing the clinical paradigms for evaluation and management. Evidence to support adopting approaches other than the current established standards should be tested through appropriately designed prospective studies.

A prospective study comparing paroxetine alone versus paroxetine plus sildenafil in patients with premature ejaculation.

PURPOSE We compared the efficacy of paroxetine alone and combined with sildenafil in patients complaining of premature ejaculation. MATERIALS AND METHODS Enrolled in this study were 80 consecutive potent men 19 to 47 years old (mean age 34) with premature ejaculation but without any obvious organic cause. Pretreatment evaluation included a history, self-administration of the International Index of Erectile Function (IIEF) questionnaire, physical examination and the Meares-Stamey test to exclude genital tract infection. The initial 40 patients received 10 mg. paroxetine daily for 21 days and then 20 mg. as needed, that is 3 to 4 hours before planned sexual activity, for 6 months (group 1). The other group of 40 men received 10 mg. paroxetine daily for 21 days and then 20 mg. as needed plus 50 mg. sildenafil as needed, that is 1 hour before planned sexual activity, for 6 months (group 2). Patients were followed 3 and 6 months after beginning therapy and were evaluated using several general assessment questions, IIEF and ejaculatory latency time. RESULTS Mean ejaculatory latency time +/- SE in group 1 was 0.33 +/- 0.04, 3.7 +/- 0.10 (p <0.01) and 4.2 +/- 0.03 (p <0.01) minutes at baseline, 3 and 6-month followup, while in group 2 it was 0.35 +/- 0.03, 4.5 +/- 0.07 (p <0.01) and 5.3 +/- 0.02 (p <0.001) minutes, respectively. When improvement in ejaculatory latency time was compared in the 2 groups, group 2 results proved to be significantly greater (p <0.05). Baseline, and 3 and 6-month mean intercourse satisfaction domain values of the IIEF were 9, 11 and 11 (p = 0.09, not significant), and 9, 11 and 14 (p <0.05) in groups 1 and 2, respectively. Group 2 patients reported significantly greater intercourse satisfaction than those in group 1 (p <0.05). At baseline, 3 and 6 months there was a mean of 0.9 +/- 0.1, 1.7 +/- 0.3 (not significant) and 2.5 +/- 0.3 (p <0.01) coitus episodes weekly in group 1, and 1 +/- 0.2, 2.3 +/- 0.3 (p <0.01) and 3.2 +/- 0.1 (p <0.001) in group 2, respectively. Group 2 patients reported a significantly higher number of coitus episodes weekly (p <0.05). Side effects in the 40 group 1 cases included anejaculation in 1 (2.5%), gastrointestinal upset and/or nausea in 5 (12.5%), headache in 4 (10%) and decreased libido in 2 (5%). Side effects in the 40 group 2 cases included anejaculation in 1 (2.5%), headache in 8 (20%), gastrointestinal upset and/or nausea in 6 (15%) and flushing in 6 (15%). Group 2 patients reported significantly more headaches (p <0.01) and flushing episodes (p <0.001) than those in group 1. After 6 months of treatment 33 men (82.5%) in group 1 and 36 (90%) in group 2 were willing to continue therapy (not significant). CONCLUSIONS Paroxetine combined with sildenafil appears to provide significantly better results in terms of ejaculatory latency time and intercourse satisfaction versus paroxetine alone in potent patients with premature ejaculation. However, combined treatment is associated with a mild increase in drug related side effects.

Long-term Outcomes of Salvage Lymph Node Dissection for Clinically Recurrent Prostate Cancer: Results of a Single-institution Series with a Minimum Follow-up of 5 Years

BACKGROUND Prostate cancer (PCa) patients with lymph node recurrence after radical prostatectomy (RP) are usually managed with androgen-deprivation therapy. Despite the absence of prospective randomized studies, salvage lymph node dissection (LND) has been proposed as an alternative treatment option. OBJECTIVE To examine long-term outcomes of salvage LND in patients with nodal recurrent PCa documented by 11C-choline positron emission tomography/computed tomography (PET/CT) scan. DESIGN, SETTING, AND PARTICIPANTS Overall, 59 patients affected by biochemical recurrence (BCR) with 11C-choline PET/CT scan with pathologic activity treated between 2002 and 2008 were included. INTERVENTION Pelvic and/or retroperitoneal salvage LND. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES Biochemical response (BR) was defined as prostate-specific antigen (PSA) <0.2 ng/ml at 40 d after surgery. BCR for those who achieved BR was defined as a PSA >0.2 ng/ml. Clinical recurrence (CR) was defined as a positive PET/CT scan after salvage LND in the presence of a rising PSA. Kaplan-Meier curves assessed time to BCR, CR, and cancer-specific mortality (CSM). Cox regression analyses were fitted to assess predictors of CR. RESULTS AND LIMITATIONS Median follow-up after salvage LND was 81.1 mo. Overall, 35 patients (59.3%) achieved BR. The 8-yr BCR-free survival rate in patients with complete BR was 23%. Overall, the 8-yr CR- and CSM-free survival rates were 38% and 81%, respectively. In multivariable analyses evaluating preoperative variables, PSA at salvage LND represented the only predictor of CR (p=0.03). When postoperative variables were considered, BR and the presence of retroperitoneal lymph node metastases were significantly associated with the risk of CR (all p ≤ 0.04). Our study is limited by the lack of a control group. CONCLUSIONS Salvage LND may represent a therapeutic option for patients with BCR after RP and nodal pathologic uptake at 11C-choline PET/CT scan. Although most patients progressed to BCR after salvage LND, roughly 40% of them experienced CR-free survival. PATIENT SUMMARY Salvage lymph node dissection may represent a therapeutic option for selected patients with nodal recurrence after radical prostatectomy. Roughly 40% of men did not show any further clinical recurrence at long-term follow-up after surgery.

Serum Isoform [−2]proPSA Derivatives Significantly Improve Prediction of Prostate Cancer at Initial Biopsy in a Total PSA Range of 2–10 ng/ml: A Multicentric European Study

BACKGROUND Strategies to reduce prostate-specific antigen (PSA)-driven prostate cancer (PCa) overdiagnosis and overtreatment seem to be necessary. OBJECTIVE To test the accuracy of serum isoform [-2]proPSA (p2PSA) and its derivatives, percentage of p2PSA to free PSA (fPSA; %p2PSA) and the Prostate Health Index (PHI)-called index tests-in discriminating between patients with and without PCa. DESIGN, SETTING, AND PARTICIPANTS This was an observational, prospective cohort study of patients from five European urologic centers with a total PSA (tPSA) range of 2-10 ng/ml who were subjected to initial prostate biopsy for suspected PCa. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary end point was to evaluate the specificity, sensitivity, and diagnostic accuracy of index tests in determining the presence of PCa at prostate biopsy in comparison to tPSA, fPSA, and percentage of fPSA to tPSA (%fPSA) (standard tests) and the number of prostate biopsies that could be spared using these tests. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision curve analysis. RESULTS AND LIMITATIONS Of >646 patients, PCa was diagnosed in 264 (40.1%). Median tPSA (5.7 vs 5.8 ng/ml; p=0.942) and p2PSA (15.0 vs 14.7 pg/ml) did not differ between groups; conversely, median fPSA (0.7 vs 1 ng/ml; p<0.001), %fPSA (0.14 vs 0.17; p<0.001), %p2PSA (2.1 vs 1.6; p<0.001), and PHI (48.2 vs 38; p<0.001) did differ significantly between men with and without PCa. In multivariable logistic regression models, p2PSA, %p2PSA, and PHI significantly increased the accuracy of the base multivariable model by 6.4%, 5.6%, and 6.4%, respectively (all p<0.001). At a PHI cut-off of 27.6, a total of 100 (15.5%) biopsies could have been avoided. The main limitation is that cases were selected on the basis of their initial tPSA values. CONCLUSIONS In patients with a tPSA range of 2-10 ng/ml, %p2PSA and PHI are the strongest predictors of PCa at initial biopsy and are significantly more accurate than tPSA and %fPSA.

Prostate-Specific Antigen (PSA) Isoform p2PSA Significantly Improves the Prediction of Prostate Cancer at Initial Extended Prostate Biopsies in Patients with Total PSA Between 2.0 and 10 ng/ml: Results of a Prospective Study in a Clinical Setting

BACKGROUND Total prostate-specific antigen (tPSA), ratio of free PSA (fPSA) to tPSA (%fPSA), and PSA density (PSAD) testing have a very low accuracy in the detection of prostate cancer (PCa). There is an urgent need for more accurate biomarkers. OBJECTIVE To compare the diagnostic accuracy of PSA isoform p2PSA and its derivatives in determining the presence of PCa at initial biopsy with the accuracy of other predictors in patients with tPSA 2.0-10 ng/ml. DESIGN, SETTING, AND PARTICIPANTS We conducted an observational prospective study in a real clinical setting of consecutive men with tPSA 2.0-10 ng/ml and negative digital rectal examination who were scheduled for prostate biopsy at a tertiary academic center. INTERVENTION Outpatient transrectal ultrasound-guided prostate biopsies were performed according to a standardized institutional saturation scheme (18-22 cores). MEASUREMENTS We determined the diagnostic accuracy of serum tPSA, %fPSA, PSAD, p2PSA, %p2PSA [(p2PSA/fPSA)×100] and the Beckman Coulter Prostate Health Index (phi; [p2PSA/fPSA×√tPSA]). RESULTS AND LIMITATIONS Overall, 107 of 268 patients (39.9%) were diagnosed with PCa at extended prostate biopsies. Statistically significant differences between patients with and without PCa were observed for age, prostate and transition zone volume, PSAD, %p2PSA, and phi (all p values<0.05). In univariate accuracy analysis, phi and %p2PSA were the most accurate predictors of PCa (area under the curve: 75.6% and 75.7%, respectively), followed by transition zone volume (66%), prostate volume (65%), patient age (63%), PSAD (61%), %fPSA (58%), and tPSA (53%). In multivariate accuracy analyses, both phi (+11%) and %p2PSA (+10%) significantly improved the accuracy of established predictors in determining the presence of PCa at biopsy (p<0.001). Although %p2PSA and phi were significantly associated with Gleason score (Spearman ρ: 0.303 and 0.387, respectively; p ≤ 0.002), they did not improve the prediction of Gleason score ≥7 PCa in multivariable accuracy analyses (p > 0.05). CONCLUSIONS In patients with a tPSA between 2.0 and 10 ng/ml, %p2PSA and phi are the strongest predictors of PCa at initial extended biopsies and are significantly more accurate than the currently used tests (tPSA, %fPSA, and PSAD) in determining the presence of PCa at biopsy.

Sildenafil taken at bedtime significantly increases nocturnal erections: results of a placebo-controlled study

OBJECTIVES Nighttime erections occur at all ages and contribute to the maintenance of the morphodynamic integrity of smooth muscle cells within the corpora cavernosa. This study was aimed at evaluating the effect on nocturnal erections of sildenafil versus a placebo taken at bedtime. METHODS A double-blind, crossover, placebo-controlled study design was used to examine the effects of sildenafil and placebo on sleep-related erectile activity. Thirty selected patients with erectile dysfunction (vasculogenic etiology, 22 patients [73%]; psychogenic etiology, 8 patients [27%]) were submitted to a polysomnographic recording of nocturnal erections, using a RigiScan device during 3 consecutive nights. After a first night of adaptation, the 2 following nights were used to study patients after the administration of sildenafil (100 mg) or a placebo taken at bedtime. RESULTS Twenty-three patients (77%) showed a significantly improved nocturnal erectile activity (according to the calculation of rigidity and tumescence activity units) after the administration of sildenafil (P <0.01), 5 patients (17%) showed comparable nocturnal erections with sildenafil and placebo, and 2 patients (6%) showed a significantly improved nocturnal erectile activity after taking the placebo (P <0.05). Overall, mean rigidity and tumescence activity values at the tip and base of the penis were significantly improved after sildenafil rather than placebo administration (P <0.001). The duration of tip rigidity greater than 60% was significantly longer during the night with sildenafil (P <0. 001). Although the number of erectile episodes was greater during the sildenafil night, this did not reach statistical significance. CONCLUSIONS In most patients with good sleep efficiency and who have erectile dysfunction, sildenafil, rather than a placebo, taken at bedtime produces a significantly improved nocturnal erectile activity. Further studies are needed to verify whether this preliminary finding may constitute the basis for the use of sildenafil as a tool for preventing erectile dysfunction.

Prognostic Value of Lymph Node Dissection in Patients with Muscle-Invasive Transitional Cell Carcinoma of the Upper Urinary Tract

OBJECTIVES To analyze the prognostic role of lymphadenectomy (LND) in patients with muscle-invasive transitional cell carcinoma (TCC) of the upper urinary tract (UUT) managed with radical surgery. METHODS From 1986 to 2003, 132 consecutive patients with muscle-invasive TCC of the UUT underwent radical surgery. LND was performed in 95 cases. Patients were stratified according to the presence of LND and lymph node (LN) status. Univariable and multivariable Cox regression models determined the effect of age, pT, grade, nodal status (pN), number of LNs removed, year of surgery, and postoperative chemotherapy on disease-free survival (DFS) and cancer-specific survival (CSS) in the overall population and in patients who underwent LND. RESULTS The actuarial 5-yr CSS in pNx patients was significantly worse than in pN0 patients (48% vs. 73%, p=0.001) and comparable to pN+ outcome (48% vs. 39%, p=0.476). In the entire population, multivariable Cox regression analyses indicated that pT and pN status were independent predictors of DFS (p=0.04, hazard ratio [HR]=1.82 and p<0.01, HR=1.34, respectively) and CSS (p<0.01, HR=2.42 and p=0.04, HR=1.32, respectively). In patients who underwent LND, the number of LNs removed was an independent predictor of DFS (p=0.03, HR=0.928) and of CSS (p=0.007, HR=0.903). The extent of LND again resulted in an independent predictor either of DFS or CSS (p=0.04, HR=0.904 and p=0.01, HR=0.867, respectively) in the subgroup of pN0 patients. CONCLUSIONS LND emerged as a strong independent predictor of DFS and CSS in patients surgically managed for a muscle-invasive TCC of the UUT.