High cancer detection rate using cognitive fusion - targeted transperineal prostate biopsies.

OBJECTIVE: MRI of the prostate improves diagnostic accuracy of prostate cancer. Different fusion approaches with transrectal ultrasound images are employed. To determine detection rate of prostate cancer in men undergoing transperineal MRIbased cognitive fusion biopsy. MATERIALS AND METHODS: One hundred and sixty-four consecutive men underwent a multiple-core prostate transperineal biopsy. Univariable and multivariable logistic regression analyses were used to address the relationship between clinical parameters and prostate cancer detection rate. RESULTS: One hundred and fourteen patients underwent mpMRI prior to the transperineal biopsy, 52 (45%) were diagnosed with prostate cancer, of them, 36 had Gleason score ≥7 (69%). Among these 114 patients, 82 had suspicious lesions on MRI, and 43 of them were diagnosed with cancer (52%). On multivariate analysis, the most significant independent predictive factors were PSA density (P<0.001) and suspicious MRI lesion (P=0.006). Men with a PSA density of more than 0.22 and a suspicious lesion on MRI had a detection rate of 78%. Detection rate among 50 patients with no MRI study prior to this biopsy was 26%. CONCLUSIONS: This study showed that among a group of mostly multi-biopsied patients, the presence of mpMRI lesions and high PSA density values helped to detect clinically significant prostate cancer using cognitive MRI/TRUS fusion biopsies.

Upper Calyx Approachability through a Lower Calyx Access for Prone Versus Supine Percutaneous Nephrolithotomy.

PURPOSE: We assessed the approachability of the upper calyx through lower calyx access for prone and supine percutaneous nephrolithotomy and used computerized tomography to analyze anatomical factors that may influence it. MATERIALS AND METHODS: A prospective series of 45 patients treated with percutaneous nephrolithotomy were operated on in the prone (20) and supine (25) positions. Computerized tomography simulated access to the lower and upper calyx longitudinal axes were used to measure skin-to-lower calyx distance, thickness of the body wall, muscle and fat, the muscle-to-fat thickness ratio and the angle between the lower calyx tract and the upper calyx axis. Intraoperative approachability to the upper calyx was also evaluated. RESULTS: The upper calyx was successfully approached in 20% of prone and 80% of supine percutaneous nephrolithotomies (p <0.0001). The average skin-to-lower calyx distance was 98.4 mm (range 65.3 to 128.6) in the prone position and 98.7 mm (range 60.8 to 150) in the supine position (p = 0.99). Body wall and muscular thickness, and the muscle-to-fat thickness ratio were significantly lower in supine than prone nephrolithotomy (p <0.001, <0.0005 and <0.05, respectively). The average angle between the lower and upper calyces axes was wide in the supine position (141 degrees, range 90 to 170) and acute in the prone position (84 degrees, range 65 to 110, p <0.05(E-10)). CONCLUSIONS: Upper calyx endoscopic approachability through the lower calyx is significantly higher in supine than in prone percutaneous nephrolithotomies, possibly due to a thinner body wall, a thinner muscular layer, a lower muscle-to-fat thickness ratio and a wider angle between the lower and upper calyx axes.

[Position statement for the diagnosis and treatment of men with benign prostate enlargement and lower urinary tract symptoms].

Benign prostate enlargement causing lower urinary symptoms is a common progressive phenomenon in adult men. Lower urinary tract symptoms may emerge during the storage, voiding, and post micturition phases, harm quality of life and may be caused by a variety of factors. The purpose of evaluation is to identify benign prostate enlargement and factors other than enlarged prostate as the cause of symptoms, and recognize the risk factors for progression of the condition. The goal of treatment is to alleviate symptoms and improve quality of life, and to prevent deterioration of symptoms and development of complications. Medical therapy is the basic approach, whereas surgery and minimally invasive procedures are reserved for patients not interested in medical therapy or for those in whom symptoms were not alleviated by means of medical therapy. In the present position statement, we present the approach to the evaluation and treatment of lower urinary tract symptoms in men with benign prostate enlargement.

A Novel Modality Enables New Evidence-Based Individual Risk Stratification That Can Potentially Lead to Decisive Management and Treatment Decisions in Prostate Cancer.

A key step in providing management/treatment options to men with suspected prostate cancer (PCa) is categorizing the risk in terms of the presence of benign, low-risk, intermediate-risk, or high-risk disease. Our novel modality brings new evidence, based on the long-known hallmark characteristic of PCa-decreased zinc (Zn), which is the most direct metabolic sign of malignancy and its aggressiveness. To date, this approach has not been adopted for clinical use for a number of reasons that are described in this article, and which have been addressed by our approach. Zn has to be measured on fresh samples, prior to fixating in formalin; therefore, samples have to be scanned during the biopsy session. As Zn depletion occurs in the glands where the tumors develop, estimation of the glands' levels in the scanned tissue, along with their compactness, are essential for accurate diagnosis. Combined with the Zn depletion, this facilitates a reliable assessment of disease aggressiveness. Data gathered in the clinical study described here indicate that, in addition to improving the biopsy quality by real-time interactive guidance, a malignancy score can now be established for the entire prostate, allowing higher granularity personalized risk stratification and more decisive treatment decisions for all PCa patients.

Validation and comparison of the two Kattan nomograms in patients with prostate cancer treated with (125) iodine brachytherapy.

UNLABELLED: Study Type - Prognostic (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Nomograms are based on large patient population. Their applicability should be externally validated. Among 747 brachytherapy patients we evaluated two Kattan nonograms and conclude that they have limited value to predict PSA-free survival. OBJECTIVE: To validate and compare the preoperative and postoperative Kattan prediction nonograms for prostate cancer recurrence after brachytherapy. PATIENTS AND METHODS: Patients (n= 747) treated with (125) I-brachytherapy were evaluated. Both nomograms were used to calculate the prediction of 5-year biochemical-freedom from failure (BFFF) based on clinical stage, Gleason score, prostate-specific antigen (PSA) level, receipt of androgen deprivation therapy and the post-implant dosimetry variable D90 (values of the minimal dose received by 90% of the prostate volume). The predicted values using the Kattan nomograms and the observed values were compared. Predictive accuracy was determined using the concordance index. RESULTS: The 5-year BFFF probability was 94% (95% confidence interval [CI], 92-96%) for the modified American Society for Radiation Oncology (ASTRO) definition and 97% (95% CI, 95-98%) for the Phoenix definition using Kaplan-Meier analysis. The predicted values of BFFF using both Kattan nomograms were lower than the observed rates in our cohort. The concordance index values were 0.51 and 0.52 for preoperative and postoperative nomograms, respectively. Concordance correlation coefficient between the two nomograms was 0.15. CONCLUSIONS: In our population, the 5-year BFFF outcomes rates were superior to nomogram predictions. Neither nomogram predicted outcomes after (125) I-brachytherapy in this non-US cohort. The postoperative nomogram was also a poor predictor, although it included D90 dosimetry values, as a variable of treatment quality. Strict inclusion criteria, perhaps more favourable than the ones on which the Kattan nomograms were based, could be the explanation for these discrepancies.

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

UNLABELLED: 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.

Endourological procedures and sexual dysfunction: a prospective multivariate analysis.

OBJECTIVE: To investigate whether endourological interventions are associated with postoperative sexual dysfunction. PATIENTS AND METHODS: The study comprises a consecutive and prospective series of patients, referred for endourological procedures. General anaesthesia was used and JJ stents were placed when required. Changes in sexual function, as assessed by the International Index of Erectile Function questionnaire that the participants filled in the day before the procedure and 1 month and up to 3 months afterwards, were analysed. RESULTS: The study group consisted of 50 men aged (mean ± SD) 45 ± 13 years, of whom 25 underwent ureteroscopy, 9 underwent retrograde intrarenal surgery (RIRS) and 16 underwent combined RIRS and percutaneous nephrolithotomy. JJ stents were postoperatively placed in 33 patients (66%). The study cohort self-reported a significant decrease in erectile function (P= 0.007), intercourse satisfaction (P < 0.001), orgasmic function (P= 0.001), sexual desire (P < 0.001) and overall satisfaction (P= 0.002) at 1 month following endourological procedures. This dysfunction was not related to chronic disease, age, smoking, preoperative or postoperative stenting, type of procedure, operative duration or surgeon expertise. The sexual function of all subjects returned to baseline within 3 months (P < 0.005). Postoperative erectile function in the stented group revealed a negative tendency that did not reach statistical significance. CONCLUSIONS: Endourological procedures are associated with temporary postoperative sexual dysfunction, which completely recovers within 3 months. The impact of postoperative stenting on sexual function was not significant. These findings contribute to enhanced preoperative patient counselling.

Can We Predict a Higher Risk of Urothelial Bladder Cancer With a Simple Blood Test?

BACKGROUND/AIM: The COVID-19 pandemic highlighted the need to develop tools prioritizing high risk patients for urgent evaluation. Our objective was to determine whether Glasgow Prognostic Score (GPS), an inflammation-based score, can predict higher grade and stage urothelial bladder cancer in patients with gross hematuria who need urgent evaluation. PATIENTS AND METHODS: We analyzed a database of 129 consecutive patients presenting with gross hematuria. GPS was calculated using pretreatment C-reactive protein (CRP) and albumin levels. Patients with bacteriuria or other known malignancies were excluded. The relationship between GPS and final diagnosis was analyzed with multivariate logistic regression. RESULTS: A total of 101 patients were included in the study and 24 patients were identified without any pathology and 77 with a bladder tumor. Pathology demonstrated 21 with muscle invasive, 18 with high grade non-muscle invasive, and 38 with low grade superficial bladder cancer. Twenty-six of 39 (67%) patients with high grade tumors had a GPS of 1 or 2 compared to only 8 out of 62 (13%) patients with either low grade or negative findings (p<0.0001). Ten of 21 (48%) patients with muscle invasive disease had a GPS of 2 compared to 1 out of 18 (6%) with high grade non muscle invasive tumors (p=0.04). On multivariate analysis, GPS was a strong independent predictor of high grade and stage bladder cancer. CONCLUSION: GPS may serve as a highly accessible predictor of high grade, high stage, and large urothelial bladder tumors at the time of initial evaluation and can help identify patients who need urgent evaluation.

The effect of delaying transperineal fusion biopsy of the prostate for patients with suspicious MRI findings-Implications for the COVID-19 era.

OBJECTIVE: Image guided biopsies are an integral part of prostate cancer evaluation. The effect of delaying biopsies of suspicious prostate mpMRI lesions is uncertain and clinically relevant during the COVID-19 crisis. We evaluated the association between biopsy delay time and pathologic findings on subsequent prostate biopsy. MATERIALS AND METHODS: After obtaining IRB approval we reviewed the medical records of 214 patients who underwent image-guided transperineal fusion biopsy of the prostate biopsy between 2017 and 2019. Study outcomes included clinically significant (ISUP grade group ≥2) and any prostate cancer on biopsy. Logistic regression was used to evaluate the association between biopsy delay time and outcomes while adjusting for known predictors of cancer on biopsy. RESULTS: The study cohort included 195 men with a median age of 68. Median delay between mpMRI and biopsy was 5 months, and 90% of patients had a ≤8 months delay. A significant association was found between PI-RADS 5 lesions and no previous biopsies and shorter delay time. Delay time was not associated with clinically significant or any cancer on biopsy. A higher risk of significant cancer was associated with older age (P = 0.008), higher PSA (0.003), smaller prostate volume (<0.001), no previous biopsy (0.012) and PI-RADS 5 lesions (0.015). CONCLUSIONS: Our findings suggest that under current practice, where men with PI-RADS 5 lesions and no previous biopsies undergo earlier evaluation, a delay of up to 8 months between imaging and biopsy does not affect biopsy findings. In the current COVID-19 crisis, selectively delaying image-guided prostate biopsies is unlikely to result in a higher rate of significant cancer.

Preoperative 68Ga-PSMA PET/CT defines a subgroup of high-risk prostate cancer patients with favorable outcomes after radical prostatectomy and lymph node dissection.

BACKGROUND: High-risk prostate cancer is associated with adverse pathology and unfavorable outcomes after radical prostatectomy. 68Ga-PSMA PET/CT is more accurate than conventional imaging for preoperative staging. We aimed to evaluate whether lymph node involvement on 68Ga-PSMA PET/CT prior to radical prostatectomy in patients with high-risk prostate cancer is associated with worse short-term oncologic outcomes. METHODS: We retrospectively reviewed 149 patients with high-risk localized or locoregional prostate cancer who underwent 68Ga-PSMA PET/CT prior to radical prostatectomy between 2015 and 2020. None of the patients received neoadjuvant or adjuvant treatment. The study endpoints were PSA persistence and biochemical recurrence. Logistic regression models were used to identify preoperative predictors of PSA persistence. Kaplan-Meier analyses were used to estimate biochemical recurrence-free survival. RESULTS: Of 149 identified patients, 19 (13%) were found to have lymph node involvement on preoperative 68Ga-PSMA PET/CT. The sensitivity, specificity, and accuracy of 68Ga-PSMA PET/CT for identifying pathologic lymph node involvement were 68%, 95%, and 92%, respectively. PSA persistence rate was lower among patients with PET-negative lymph nodes than those with PET-positive nodes (15 vs. 84%, p < 0.001). Positive nodes on imaging (OR = 41.03, p < 0.001) and clinical T2c-T3 stage (OR = 6.96, p = 0.002) were associated with PSA persistence on multivariable analysis. Among patients with PET-negative nodes the 1- and 2-year biochemical recurrence-free survival rates were 87% and 76%, respectively. CONCLUSIONS: Preoperative staging with 68Ga-PSMA PET/CT may identify a subgroup of high-risk prostate cancer patients with favorable short-term outcomes after radical prostatectomy without adjuvant treatment. Future studies will evaluate whether these results are sustained during long-term follow-up.

Tubeless percutaneous nephrolithotomy: first 200 cases in Israel.

BACKGROUND: Tubeless percutaneous nephrolithotomy is defined as PCNL without postoperative nephrostomy tubes. It is reported to reduce postoperative pain, hospital stay and recovery time. To date the procedure has been reserved for selected patients. OBJECTIVES: To assess our initial experience in extending the implementation of tubeless PCNL without preoperative patient selection. METHODS: All consecutive PCNLs performed during 2004-2008 were evaluated. Tubeless PCNL was performed when residual stones, bleeding and extravasation were excluded intraoperatively. Staghorn stones, stone burden, supracostal and multiple accesses, anatomic anomalies, solitary kidneys and operative time were not considered contraindications. We analyzed the clinical data and the choice of tubeless PCNL over time. RESULTS: Of 281 PCNLs performed during the study period 200 (71%) were tubeless. The patients' average age was 53 years (range 28-82 years), the stone burden was 924 mm2 (400-3150 mm2), operative time was 99 minutes (45-210 min), complication rate was 14% and immediate stone-free rate 91%. There were 81 conversions to standard PCNL (29%) due to expected second-look (n = 47, 58%), impression of bleeding (n = 21,26%), suspected hydrothorax (n = 7, 9%) and extravasation (n = 6, 7%). The transfusion rate was 1%. The median hospital stay was 1 day (1-15 days) and recovery time 7 days (5-20 days). The rate of implementing the tubeless procedure increased steadily along time from 46% to 83% (P = 0.0001). CONCLUSIONS: Tubeless PCNL can be safely and effectively performed based on intraoperative decisions, without preoperative contraindications. They are easily accommodated by experienced endourologists and provide real advantages.

Detection of prostate specific transcripts in the peripheral blood during brachytherapy predicts postoperative PSA kinetics.

BACKGROUND: We evaluated whether detection of prostate-specific antigen (PSA) and human kallikrein 2 (hK2) transcripts in the peripheral blood during brachytherapy could predict biochemical outcome. METHODS: Eighty-one patients who underwent (125)Iodine-based brachytherapy for localized prostate cancer (Gleason score <8, PSA <20 ng/ml, stage

Long-term biochemical progression-free survival following brachytherapy for prostate cancer: Further insight into the role of short-term androgen deprivation and intermediate risk group subclassification.

INTRODUCTION: Brachytherapy is a well-established treatment of localized prostate cancer. Few studies have documented long-term results, specifically biochemical progression-free survival (bPFS) in men with brachytherapy alone, with or without short-term androgen deprivation therapy (ADT), or in combination with external beam radiotherapy (EBRT). Our aim was to analyze long-term bPFS of brachytherapy treated patients. MATERIALS AND METHODS: Retrospective analysis of 1457 patients with low and intermediate risk prostate cancer treated with brachytherapy alone (1255) or combined with EBRT (202). Six-months ADT was administrated for all EBRT combined patients and for prostate volume downsizing when >55 cc (328). Failure was by the Phoenix definition. Kaplan-Meier analysis and multivariate Cox regression estimated and compared 10-yr and 15-yr rates of bPFS. RESULTS: Median follow-up was 6.1 yr. Ten and 15-yr bPFS rates of the entire cohort were 93.2% and 89.2%, respectively. On multivariate analysis, PSA density (PSAD), ADT and clinical stage were significantly associated with failure. The most powerful independent factor was PSAD with a HR of 3.5 (95% CI, 1.7-7.4) for PSAD above 0.15. No significant difference was found between low and intermediate risks patients regardless of treatment regimen. However, comparison of two intermediate risk groups, Gleason score (GS) 7, PSA<20 ng/ml versus GS≤6 and PSA = 10-20 ng/ml, revealed 10- and 15-yr bPFS rates of 94.2% and 94.2% compared to 88.2% and 79.9%, (P = 0.022), respectively. ADT improved bPFS rates in low risk patients. The ten and 15-yr bPFS rates were 97.6% and 94.6% compared to 92.3% and 88.2%, (P = 0.020), respectively. CONCLUSIONS: Our retrospective large scale study suggests that brachytherapy provides excellent long-term bPFS rates in low and intermediate risk disease. Combination of brachytherapy with EBRT yields favorable outcomes in GS 7 intermediate risk patients and short-term ADT has a positive effect on outcomes in low risk patients. Further prospective studies are warranted to discriminate the role of adding either EBRT and/or ADT to brachytherapy protocols.

Alfuzosin 10 mg once daily for treating benign prostatic hyperplasia: a 3-year experience in real-life practice.

OBJECTIVES: To assess the 3-year efficacy and safety of the selective alpha(1)-blocker alfuzosin at 10 mg once daily in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) in 'real-life practice'. The influence of treatment response on the risk of acute urinary retention (AUR) and BPH-related surgery was also analysed. PATIENTS AND METHODS: In all, 689 European men (mean age 67.6 years) were enrolled by general practitioners in a 3-year open-label study with alfuzosin at 10 mg once daily. They were asked to complete the International Prostate Symptom Score (IPSS), its eighth question (bother score), and the Danish Prostatic Symptom Score for sexual function (DAN-PSSsex). Efficacy was analysed at the endpoint in the intent-to-treat population. The impact of baseline variables (age, PSA level, IPSS and bother severity) and dynamic variables (IPSS worsening of >or=4 points and bother at the last available assessment under treatment) on the risk of AUR and BPH-related surgery was evaluated. RESULTS: With alfuzosin, IPSS improved by 6.4 points (-33.4%) from baseline (P < 0.001), reaching >or=3 points and >6 points in 71.3% and 47.2% of men, respectively. There were also significant (P < 0.001) improvements from baseline in nocturia (-0.8, -25.5%), bother score (-1.7, -40.7%) and DAN-PSSsex weighted scores with treatment. Symptom relief was rapid and maintained over 3 years. Overall, 78 men (12.4%) had an IPSS worsening of >or=4 points, 16 (2.6%) had AUR, and 36 (5.7%) required BPH-related surgery. Symptom deterioration during treatment and high baseline PSA values were the best predictors of AUR and BPH-related surgery. Alfuzosin was well tolerated, dizziness being the most frequent adverse event (4.5%) possibly related to vasodilatation. Ejaculatory disorders were uncommon (0.4%). Changes in blood pressure remained marginal, including in men aged >or=65 years and those receiving antihypertensive agents. CONCLUSION: Alfuzosin administered for 3 years at 10 mg once daily in real-life practice is effective and well tolerated. High PSA values and symptom worsening under treatment appear the best predictors of AUR and BPH-related surgery in the long term. Treatment with alfuzosin might thus help to identify patients at risk of LUTS/BPH progression in order to optimize their management.

MSF-A interacts with hypoxia-inducible factor-1alpha and augments hypoxia-inducible factor transcriptional activation to affect tumorigenicity and angiogenesis.

Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor in the signaling pathway that controls the hypoxic responses of cancer cells. Activation of the HIF system has been observed in carcinogenesis and numerous cancers. We found an interaction between a member of the mammalian septin gene family (MSF-A) and the HIF system. MSF-A is a nuclear protein that interacts with HIF-1alpha protein to prevent its ubiquitination and degradation, thus activating the HIF transcriptome. Cells overexpressing MSF-A protein exhibit increased HIF transcriptional activity and higher proliferation rates in vitro and in vivo. Xenograft-derived human tumors from these cells were larger and more vascular. These findings link a function of a septin protein with angiogenesis through activation of the HIF pathway.

[Alpha blockers in use for symptomatic benign prostatic hyperplasia--are all drugs born equal?].

Alpha-adrenergic blockers are an established form of medical treatment for symptomatic benign prostatic hyperplasia (BPH). Several medications of the class are available, each with its own characteristics. The authors attempted to define the differences between the currently available medications (Terazosin, Doxazosin, Alfuzosin, and Tamsulosin), and to present an evidence-based recommendation for choosing the best treatment option. A literature search was conducted, using Medline queries and the references of review papers, in search of pertinent studies. These included controlled studies comparing the results of treatment with alpha blockers to placebo, or direct comparative studies of alpha blockers, and real life practice, community studies of each of the medications. A similar efficacy emerged from the reviewed articles, but with a different adverse events profile. A higher rate of vasodilatatory, cardiovascular side effects (dizziness, fatigue, and hypotension) was observed with terazosin and doxazosin, when compared with the uroselective alfuzosin and tamsulosin. Of the latter two, hypotension was more frequent with alfuzosin, while ejaculatory dysfunction was more frequent with tamsulosin. In conclusion, each of the four medications is a possible treatment option for BPH, but we believe alfuzosin and tamsulosin are the better choice. In light of an identical efficacy, these medications offer better tolerability, and ease of use of a once daily treatment without dose titration. The choice between the two should be tailored to the individual patient, with alfuzosin associated with hypotensive side effects, and tamsulosin causing ejaculatory dysfunction.

Can urologists accurately stage and grade urothelial bladder cancer by assessing endoscopic photographs?

Introduction Assessment of urothelial bladder cancer during cystoscopy or transurethral resection of bladder tumour has a significant impact on the urologist's decision-making: treatment with simple outpatient fulguration, required depth of resection, and need of immediate post-surgical intravesical therapy. These choices depend heavily on the urologist's ability to accurately assess pre-biopsy tumour stage and grade. The aim of the study was to determine whether evaluation of photographs taken during transurethral resection of bladder tumour can reliably characterize a tumour's stage and grade. Methods Smartphone photographs of 50 urothelial bladder cancer cases were taken at the beginning of transurethral resection of bladder tumour and individually presented to seven senior urologists. All urologists were blinded to the final pathological report and to any other urological evaluation. Each one was asked to rate the tumour as low vs high grade and noninvasive Ta vs noninvasive T1 or muscle invasive. Results were compared with final pathology. Individual appraisal and the majority's opinion were evaluated. Results Urologists have correctly predicted tumour stage and grade in 63.5% of cases (222 of 350, average of 32 out of 50 accurate assessments). The final majority assessment was correct in 40 of 50 cases (80%). Sensitivity and specificity of the final results for the diagnosis of T1 or higher were 80% and 88.6%, respectively. Sensitivity and specificity for Ta low grade were 83.3% and 80%, respectively. Conclusions To the best of our knowledge, this is the first documented attempt to evaluate urologists' ability to assess urothelial bladder cancer stage and grade using endoscopic photographs. Urologists can usually identify stage and grade of urothelial bladder cancer but accuracy increases when multiple senior urologists examine the same photographs and achieve majority consensus. Presenting photographs of urothelial bladder cancer to a team of urologists may lead to an excellent decision regarding type and extent of surgical treatment and substantiate appropriate post-surgical management.

A Novel Urine-Based Assay for Bladder Cancer Diagnosis: Multi-Institutional Validation Study.

BACKGROUND: CellDetect is a unique histochemical stain enabling color and morphological discrimination between malignant and benign cells based on differences in metabolic signature. OBJECTIVE: The objective of the present study was to validate the performance of this assay in a controlled, blinded, multicenter study. DESIGN, SETTING, AND PARTICIPANTS: The study, conducted in nine hospitals, included patients with documented history of bladder cancer, monitored for urothelial carcinoma (UCC) or scheduled for bladder cancer surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cystoscopy and/or biopsy were used as a reference standard to determine sensitivity and specificity. Smears were stained by CellDetect and interpreted by two cytologists blinded to the patient's final diagnosis. The findings were compared with those of standard urine cytology and BTA stat. RESULTS AND LIMITATIONS: Two hundred and seventeen voided urine specimens were included. Ninety-six (44%) were positive by histology and 121 (56%) were negative by either cystoscopy or histology. The overall sensitivity of CellDetect was 84%. Notably, the sensitivity for detecting low-grade nonmuscle-invasive bladder cancer tumors was greater than this of BTA stat (78% vs 54%) and more than two-fold higher compared with standard cytology (33%, p ≤ 0.05). The specificity was 84% in patients undergoing routine surveillance by cystoscopy. At a median follow-up of 9 mo, 21% of the patients with positive CellDetect and negative reference standard developed UCC, which was significantly higher compared with the 5% of the true negative cases. Limitations include the lack of instrumental urine samples and the lack of patients with nongenitourinary cancers in the study population. CONCLUSIONS: This study validates the performance of CellDetect as a urine-based assay to identify UCC in patients with history of bladder cancer. The high sensitivity was maintained across all cancer grades and stages without compromising the assay specificity. Further studies are required to test whether this novel stain can be incorporated in routine bladder cancer surveillance as a noninvasive alternative to cystoscopy. PATIENT SUMMARY: Surveillance of bladder cancer requires frequent invasive procedures. In the present study, we validate the ability of a novel biomarker to accurately identify early-stage tumors in urine specimens for the noninvasive monitoring of patients with history of bladder cancer.

The homozygous P582S mutation in the oxygen-dependent degradation domain of HIF-1 alpha is associated with increased risk for prostate cancer.

BACKGROUND: The heterodimeric transcription factor HIF-1 (hypoxia-inducible factor 1), consisting of a critically regulated HIF-1 alpha subunit and a constitutively expressed HIF-1 beta subunit, is a master regulator of genes involved in adaptation and survival under low-oxygen conditions. Increased levels of HIF-1 activity are associated with increased tumor aggressiveness, therapeutic resistance, and mortality. METHODS: We studied 402 prostate cancer patients for the presence of the 1772C > T (P582S) and 1790G > A (A588T) mutations within the oxygen-dependent domain of HIF-1 alpha. RESULTS: Homozygosity for the P582S mutation was fourfold greater among prostate cancer patients compared to controls (OR = 4.10 [C.I. 95% 1.11 < OR < 17.87], P = 0.018). The existence of this mutation in prostate cancer patients was not associated with any of the clinical or pathological characteristics of the disease. No significant differences were found between the frequencies of A588T mutation in prostate cancer patients and controls. CONCLUSIONS: Our data suggest that homozygous HIF1A P582S mutation confers significant susceptibility to prostate cancer.