Validation of a 2-gene mRNA urine test for the detection of ≥GG2 prostate cancer in an opportunistic screening population.

BACKGROUND: A 2-gene urine-based molecular test that targets messenger RNAs known to be overexpressed in aggressive prostate cancer (PCa) has been described as a helpful method for detecting clinically significant prostate cancer (grade group [GG] ≥2). We performed an external validation of this test in men undergoing initial prostate biopsy (Bx) within a Spanish opportunistic screening scenario. METHODS: We analyzed archived samples from 492 men who underwent prostate Bx in an opportunistic screening scenario, with prostate-specific antigen (PSA) 3 to 10 ng/mL and/or suspicious digital rectal exploration (DRE) and without previous multi-parametric magnetic resonance imaging (mpMRI). Urinary biomarker measurements were combined with clinical risk factors to determine a risk score, and accuracy for GG ≥ 2 PCa detection was compared with PCA3, European randomized screening in prostate cancer (ERSPC), and prostate biopsy collaborative group (PBCG) risk calculators in a validation workup that included calibration, discrimination, and clinical utility analysis. RESULTS: In our cohort, the detection rates for GG1 and GG ≥ 2 PCa were 20.3% and 14.0%, respectively. The median PSA level was 3.9 ng/mL and 13.4% of subjects had suspicious DRE findings. The median risk score for men with GG ≥ 2 PCa was 21 (interquartile range: 14-28), significantly higher than benign+GG1 PCa (10, 6-18), P < .001, achieving the highest area under the curve among the models tested, 0.749 (95% confidence interval: 0.690-0.807). The urine test was well-calibrated, while ERSPC showed a slight underestimation and PBCG a slight overestimation of risk. Assuming a GG2 non-detection rate of 11% without using mpMRI, use of the urinary biomarker-based clinical model could have helped avoid 37.2% of excess biopsies while delaying the diagnosis of eight patients (1.6% of the entire cohort) with GG ≥ 2 PCa. CONCLUSIONS: In this first evaluation in an opportunistic screening population, the urinary biomarker-based test improved the detection of clinically significant PCa. Facing men with elevated PSA and/or suspicious DRE, it could be a useful tool to help avoid excess initial Bx and to identify patients most likely to benefit from Bx.

Ex-vivo confocal fluorescence microscopy for rapid evaluation of renal core biopsy.

Small renal mass incidentally diagnosed are common findings nowadays due to the widespread of imaging. Renal mass biopsy is still underutilized by urologists due to its non-diagnostic rates. Confocal microscopy allows for rapid imaging of fresh tissue samples. We report the feasibility of using confocal technology for determining the quality of the renal core at renal mass biopsy on 4 consecutive cases at our institution.

Functional follow-up after Advance® and Advance XP® male sling surgery: assessment of predictive factors.

PURPOSE: To evaluate the efficacy of the Advance® and AdvanceXP® slings in men with stress urinary incontinence (SUI) post-radical prostatectomy and to identify predictive factors for outcome. METHODS: Included were male patients with SUI following radical prostatectomy who had a positive "repositioning test", 24 h-pad weight (PW) test < 400 g and who were continent at night and at rest. Urgency was defined as a sudden compelling desire to pass urine, which was difficult to defer. The cure rate was defined as no pad use. RESULTS: From February 2008 to October 2014, 24 AdVance® and 70 AdVance XP® were implanted. The median (range) follow-up was 49 (12-102) months. The overall cure rate was 77%. The preoperative 24 h PW was significantly related to the continence outcome (p = 0.044). A total of 12 patients (13%) presented with postoperative AUR, which was significantly related to abnormal voiding detrusor activity (p = 0.036). Twenty-two patients (23%) had postoperative urgency (16% "de novo"), which was significantly related to preoperative urgency (p = 0.003). During follow-up, a degree of deterioration of continence was observed in five patients who were classed as cured initially. To date, no reports of urethral sling erosion have been made. CONCLUSIONS: The AdVance® and AdVanceXP® slings are safe and effective in relieving SUI following post-radical prostatectomy. There were no differences between the two slings in terms of efficacy, urgency or postoperative AUR. There was a moderate rate of "de novo "urgency and low rate of loss of continence during follow-up.

Optimizing the clinical utility of PCA3 to diagnose prostate cancer in initial prostate biopsy.

BACKGROUND: PCA3 has been included in a nomogram outperforming previous clinical models for the prediction of any prostate cancer (PCa) and high grade PCa (HGPCa) at the initial prostate biopsy (IBx). Our objective is to validate such IBx-specific PCA3-based nomogram. We also aim to optimize the use of this nomogram in clinical practice through the definition of risk groups. METHODS: Independent external validation. Clinical and biopsy data from a contemporary cohort of 401 men with the same inclusion criteria to those used to build up the reference's nomogram in IBx. The predictive value of the nomogram was assessed by means of calibration curves and discrimination ability through the area under the curve (AUC). Clinical utility of the nomogram was analyzed by choosing thresholds points that minimize the overlapping between probability density functions (PDF) in PCa and no PCa and HGPCa and no HGPCa groups, and net benefit was assessed by decision curves. RESULTS: We detect 28% of PCa and 11 % of HGPCa in IBx, contrasting to the 46 and 20% at the reference series. Due to this, there is an overestimation of the nomogram probabilities shown in the calibration curve for PCa. The AUC values are 0.736 for PCa (C.I.95%:0.68-0.79) and 0.786 for HGPCa (C.I.95%:0.71-0.87) showing an adequate discrimination ability. PDF show differences in the distributions of nomogram probabilities in PCa and not PCa patient groups. A minimization of the overlapping between these curves confirms the threshold probability of harboring PCa >30 % proposed by Hansen is useful to indicate a IBx, but a cut-off > 40% could be better in series of opportunistic screening like ours. Similar results appear in HGPCa analysis. The decision curve also shows a net benefit of 6.31% for the threshold probability of 40%. CONCLUSIONS: PCA3 is an useful tool to select patients for IBx. Patients with a calculated probability of having PCa over 40% should be counseled to undergo an IBx if opportunistic screening is required.

[Dynamic sentinel node biopsy in penile cancer. Indications, technique and results in a Spanish oncological center]. / BIOPSIA DINÁMICA DE GANGLIO CENTINELA EN CÁNCER DE PENE. INDICACIONES, TÉCNICA Y RESULTADOS EN UN CENTRO ONCOLÓGICO ESPAÑOL.

OBJECTIVE: Penile cancer has a predominantly lymphatic dissemination. Lymph nodes metastatic involvement conditions disease prognosis and inguinal lymph node dissection has both prognostic and therapeutic value. High and intermediate risk patients with non-palpable lymph nodes will benefit of a precise diagnosis by means of selective sentinel node biopsy with minimal surgical aggressiveness. METHODS: Retrospective review of our experience on dynamic sentinel node biopsy in penile cancer from November 1999 to July 2014. RESULTS: We performed this procedure in 33 patients, technically successful in 29 (88%). The patients who did not undergo lymph node dissection due to positive sentinel node biopsy have been followed a mean of 60.4 months (Median 59, range 5-145). 20 patients underwent simultaneous sentinel node biopsy and surgical treatment of the primary lesion and in 13 it was performed posteriorly. In these cases the time lapse was 5.5 months (median 5, range 2-12). In 6 (18.9%) of the 29 patients successfully biopsied, metastasis was founded in any of the lymph nodes identified as sentinel. Two patients were false negative (6,25%). Sensitivity (S), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of successfully performed sentinel node biopsies were 66, 100, 100 and 93%, respectively. CONCLUSION: Sentinel node biopsy enables a correct lymph node staging avoiding the morbidity of inguinal lymph node dissection. The rate of technical failure and false negative results is low and it may be considered the diagnostic technique of choice in high and intermediate risk penile cancer with non-palpable lymph nodes.

Restaging transurethral resection of bladder tumor for high-risk stage Ta and T1 bladder cancer.

Bladder cancer is the most common malignancy of the urinary tract. About 75%-85% of patients present with non-muscle-invasive bladder cancer (NMIBC). However, patients with pT1 tumors, as well as all those with high-grade disease, make up a subset with a high-risk of recurrence and disease progression. Although still regarded as the gold standard, clinical evidence from contemporary published series clearly demonstrates that transurethral resection of tumor (TUR) is a procedure far from optimal, highlighting its limitations and the need for further diagnostic accuracy. Routine use of a restaging TUR (re-TUR), supported by the American Urological Association and European Association of Urology guidelines, detects residual tumor in a significant number of cases after initial TUR. It provides a more accurate staging of the disease and, consequently, helps to guide its treatment. Recent years have seen rapid development of novel optical techniques aimed to optimize resection. Routine implementation of these novel techniques in the context of re-TUR is promising and may potentially result in more tumors being identified and completely resected, leading to significantly lower residual tumor rates than with the standard white-light TUR. This article will focus on re-TUR in the management of high-risk NMIBC, with an up-to-date review of the available literature and detailed analysis of the published series.

Feasibility of radical transurethral resection as monotherapy for selected patients with muscle invasive bladder cancer.

PURPOSE: We proved the feasibility of radical transurethral bladder tumor resection in selected patients with muscle invasive bladder cancer with a minimum followup of more than 15 years and investigated the impact of patient age on survival. A followup schedule was developed based on progression and recurrence during this period. MATERIALS AND METHODS: A phase II nonrandomized trial was designed including patients with muscle invasive bladder cancer with negative biopsies of tumor bed who were apparently healthy after undergoing complete transurethral bladder tumor resection. Patients with positive biopsies, or with macroscopically residual tumor, hydronephrosis or metastasis were excluded from study. In this trial 133 patients fulfilled the inclusion criteria and had a minimum followup of more than 15 years. RESULTS: Cancer specific survival was 81.9%, 79.5% and 76.7%, and progression-free survival with bladder preservation was 75.5%, 64.9% and 57.8% at 5, 10 and 15 years, respectively. Patient age had a negative impact on overall survival on univariate (HR 0.842, p = 0.049) and multivariate analyses (HR 1.062, p = 0.000), and according to median and quartile age stratifications (p = 0.000 and p = 0.000, respectively). However, age did not have a negative impact on cancer specific survival even when following the same stratifications. Although progression and recurrence were concentrated during the first 3 years (70% and 65%, respectively), both steadily increased afterward. A followup schedule was developed according to this sequence of events. CONCLUSIONS: Radical transurethral bladder tumor resection is a reliable therapeutic approach for patients with muscle invasive bladder cancer after complete tumor resection and with negative biopsies of the tumor bed. These results are consistent in all age ranges.

[Pharmacological treatment for stress urinary incontinence in prostate cancer]. / Tratamiento farmacológico de la incontinencia urinaria post prostatectomía radical.

Stress urinary incontinence (SUI) is a symptom appearing in both males and females. Pharmacological treatment has demonstrated to be effective for female SUI, but its role for treatment in males is controversial. This review evaluates the various types of drugs, their effects, and levels of efficacy in the studies.

Bladder preservation in selected patients with muscle-invasive bladder cancer by complete transurethral resection of the bladder plus systemic chemotherapy: long-term follow-up of a phase 2 nonrandomized comparative trial with radical cystectomy.

BACKGROUND: Many phase 2 bladder-sparing programmes using transurethral resection of the bladder (TURB) plus chemotherapy or radio-chemotherapy have been undertaken, but some controversies remain. OBJECTIVE: To determine the efficacy of complete TURB plus three cycles of cisplatin-based chemotherapy in selected patients with muscle-invasive bladder cancer (MIBC). DESIGN, SETTING, AND PARTICIPANTS: A phase 2 nonrandomized trial was designed that included patients with MIBC who underwent complete TURB with positive biopsies of the tumour bed. Patients with negative biopsies of the tumour bed, with macroscopically residual tumour, with hydronephrosis, or with distant metastasis were excluded from this trial. Patients included in this trial were offered three cycles of systemic chemotherapy or radical cystectomy (RC). Clinical response (cR) was denoted by either no tumour or the presence of Ta1-Tis bladder tumour at 3-mo evaluation; clinical non-response (cNR) was denoted by cases of muscle-invasive tumour or distant metastasis. Of 146 patients who entered this trial, 75 choose the bladder-sparing programme and 71 chose RC. MEASUREMENTS: At 5 yr and 10 yr, the cancer-specific survival (CSS) rate was 64.5% and 59.8%, respectively, with no significant difference compared to the RC arm (p=0.544). The progression-free survival with bladder preserved was 52.6% and 34.5%, respectively. In multivariate analysis, cR was the only predictive factor for survival (p=0.001) and bladder preservation (p=0.000). RESULTS AND LIMITATIONS: This was not a randomized trial, and patients were included over 16 yr. However, no modifications were made to the therapy schedule except from chemotherapy schemes considered standard at the time. CONCLUSIONS: Patients with microscopic residual cancer after complete TURB seem to be good candidates for the bladder-sparing programme using three cycles of systemic chemotherapy, with CSS comparable to RC.

[Which patients with stress urinary incontinence after radical prostatectomy benefit from the indication of an Invance?]. / ?Qué pacientes con incontinencia de esfuerzo tras prostatectomía radical se benefician de la indicación de Invance?

OBJECTIVES: Stress urinary incontinence alter radical prostatectomy is one of the most worrisome sequelae for the patient and urologist. The aim of this paper is to evaluate the indications of the suburethral mesh Invance, giving details on our preoperative evaluation and indication, surgical technique, and the correlation between preoperative findings and functional results. METHODS: Between February 2006 and January 2009 27 patients underwent surgery. All of them had more than one year of follow up after prostatectomy, urodynamic study and preoperative cystoscopy. Continence was evaluated by the number of pads/day and the ICIQ-UI SF questionnaire. Through a perineal incision three titanium screws with a polipropylene suture were inserted in each ischiopubic rami, and a silicon/polipropylene mesh (Invance) is affixed to them, compressing the bulbar urethra. Patients were divided into two groups: good prognosis (1-2 pads/day without urodynamic anomalies in the filling phase) and bad prognosis (3 pads/day, history of radiotherapy or bladder neck incision, and urodynamic anomalies). Cure was defined as a patient not needing pads, and improvement was defined as decrease in the number of pads per day. RESULTS: Median follow up after Invance was 18 months (4-38). Nine patients used one pad/day, 10 used two, and eight used three pads /day. Six cases had underwent previous bladder neck incision and three radiotherapy. Globally, 20 patients (74% ) were cured and five (19% ) had improved. Cure rate was 100% in the good prognosis group and 61% in the bad prognosis group (p=0.03). No intraoperative complications were registered. During the immediate postoperative period,one patient required cystostomy tube for 10 days. Seven patients (26% ) presented perineal discomfort; neither de novo urgency nor urethral erosion nor sling explants due to infection were registered. CONCLUSIONS: Invance is a safe technique that guarantees a high continence rate in selected patients. It is a reproducible operation and, with a midterm follow up, no loss of continence has been observed, and the risk of urethral erosion is null in our experience. Patients with mild-moderate incontinence, without urodynamic anomalies nor previous radiotherapy are the ideal candidates.

Detrusor quantitative morphometry in obstructed males and controls.

PURPOSE: We studied the usefulness of computer assisted morphometry for measuring detrusor muscle cell diameter and the connective tissue-to-smooth muscle ratio in patients with bladder outlet obstruction, acute urinary retention and a nonobstructed control group. MATERIALS AND METHODS: A prospective study was done in patients with bladder outlet obstruction undergoing transurethral prostate resection. Patients were divided into 33 with obstruction and 14 in acute urinary retention. A total of 15 males without obstruction undergoing transurethral prostate resection for bladder tumor formed the control group. Detrusor specimens were obtained during transurethral prostate resection. Detrusor muscle cell diameter was measured using light microscopy and a semiautomatic image analysis system. The connective tissue-to-smooth muscle ratio was automatically determined with computer assisted image analysis. Symptoms and urodynamic assessment were performed preoperatively and 6 months postoperatively. RESULTS: A total of 62 patients were included. The obstruction and acute urinary retention groups had a statistically higher detrusor muscle cell diameter and more fibrosis than the control group. Patients in acute urinary retention had more intrafascicular fibrosis (higher connective tissue-to-smooth muscle ratio at 40x magnification) than patients with obstruction. There were no differences in detrusor muscle cell diameter or interfascicular fibrosis (connective tissue-to-smooth muscle ratio at 10x magnification) between the obstruction and acute urinary retention groups. Detrusor muscle cell diameter correlated with symptom duration and functional recovery after transurethral prostate resection. Detrusor fibrosis correlated with preoperative detrusor pressure at maximum flow and postoperative compliance. Patients in acute urinary retention had fewer symptoms and higher residual volume. Other urodynamic parameters and their improvement after surgery were similar in the acute urinary retention and obstruction groups. CONCLUSIONS: Morphometric differences in detrusor muscle cell diameter and the connective tissue-to-smooth muscle ratio were observed between controls and patients with obstruction. There is an increase in detrusor muscle cell diameter and fibrosis in bladder outlet obstruction and more intense intrafascicular collagen deposition in patients in acute urinary retention.

Is it necessary to shave the pubic and genital regions of patients undergoing endoscopic urological surgery?

To determine whether postoperative urinary infections were related to shaving before undergoing endoscopic urological surgery, 90 patients were randomly assigned to shaving or not shaving. Urinary cultures revealed infection in 10 patients. Half of them had been shaved, suggesting that this practice does not affect the incidence of urinary infections.