Diagnosis of prostate cancer with magnetic resonance imaging in men treated with 5-alpha-reductase inhibitors.

PURPOSE: The primary aim of this study was to evaluate if exposure to 5-alpha-reductase inhibitors (5-ARIs) modifies the effect of MRI for the diagnosis of clinically significant Prostate Cancer (csPCa) (ISUP Gleason grade ≥ 2). METHODS: This study is a multicenter cohort study including patients undergoing prostate biopsy and MRI at 24 institutions between 2013 and 2022. Multivariable analysis predicting csPCa with an interaction term between 5-ARIs and PIRADS score was performed. Sensitivity, specificity, and negative (NPV) and positive (PPV) predictive values of MRI were compared in treated and untreated patients. RESULTS: 705 patients (9%) were treated with 5-ARIs [median age 69 years, Interquartile range (IQR): 65, 73; median PSA 6.3 ng/ml, IQR 4.0, 9.0; median prostate volume 53 ml, IQR 40, 72] and 6913 were 5-ARIs naïve (age 66 years, IQR 60, 71; PSA 6.5 ng/ml, IQR 4.8, 9.0; prostate volume 50 ml, IQR 37, 65). MRI showed PIRADS 1-2, 3, 4, and 5 lesions in 141 (20%), 158 (22%), 258 (37%), and 148 (21%) patients treated with 5-ARIs, and 878 (13%), 1764 (25%), 2948 (43%), and 1323 (19%) of untreated patients (p < 0.0001). No difference was found in csPCa detection rates, but diagnosis of high-grade PCa (ISUP GG ≥ 3) was higher in treated patients (23% vs 19%, p = 0.013). We did not find any evidence of interaction between PIRADS score and 5-ARIs exposure in predicting csPCa. Sensitivity, specificity, PPV, and NPV of PIRADS ≥ 3 were 94%, 29%, 46%, and 88% in treated patients and 96%, 18%, 43%, and 88% in untreated patients, respectively. CONCLUSIONS: Exposure to 5-ARIs does not affect the association of PIRADS score with csPCa. Higher rates of high-grade PCa were detected in treated patients, but most were clearly visible on MRI as PIRADS 4 and 5 lesions. TRIAL REGISTRATION: The present study was registered at ClinicalTrials.gov number: NCT05078359.

The Role of miRNA in Testicular Cancer: Current Insights and Future Perspectives.

Background and Objectives: Despite advancements in the diagnosis and treatment of testicular germ cell tumours (TGTCs), challenges persist in identifying reliable biomarkers for early detection and precise disease management. This narrative review addresses the role of microRNAs (miRNAs) as potential diagnostic tools and therapeutic targets in the treatment of TGCTs. Materials and Methods: Three databases (PubMed®, Web of Science™, and Scopus®) were queried for studies investigating the utility of miRNA as diagnostic tools, assessing their prognostic significance, and evaluating their potential to guide TGCT treatment. Different combinations of the following keywords were used, according to a free-text protocol: "miRNA", "non-coding RNA", "small RNA", "Testicular Cancer", "seminomatous testicular germ cell", "non-seminomatous testicular germ cell". Results: The potential of miRNAs as possible biomarkers for a non-invasive diagnosis of TGCT is appealing. Their integration into the diagnostic pathway for TGCT patients holds the potential to enhance the discriminative power of conventional serum tumour markers (STMs) and could expedite early diagnosis, given that miRNA overexpression was observed in 50% of GCNIS cases. Among miRNAs, miR-371a-3p stands out with the most promising evidence, suggesting its relevance in the primary diagnosis of TGCT, particularly when conventional STMs offer limited value. Indeed, it demonstrated high specificity (90-99%) and sensitivity (84-89%), with good positive predictive value (97.2%) and negative predictive value (82.7%). Furthermore, a direct relationship between miRNA concentration, disease burden, and treatment response exists, regardless of disease stages. The initial evidence of miRNA decrease in response to surgical treatment and systemic chemotherapy has been further supported by more recent results suggesting the potential utility of this tool not only in evaluating treatment response but also in monitoring residual disease and predicting disease relapse. Conclusions: MiRNAs could represent a reliable tool for accurate diagnosis and disease monitoring in the treatment of TGCT, providing more precise tools for early detection and treatment stratification. Nevertheless, well-designed clinical trials and comprehensive long-term data are needed to ensure their translation into effective clinical tools.

The impact of race/ethnicity on upstaging and/or upgrading rates among intermediate risk prostate cancer patients treated with radical prostatectomy.

BACKGROUND: Race/ethnicity may predispose to less favorable prostate cancer characteristics in intermediate risk prostate cancer (IR PCa) patients. We tested this hypothesis in a subgroup of IR PCa patients treated with radical prostatectomy (RP). METHODS: We relied on the Surveillance, Epidemiology and End Results 2004-2016. The effect of race/ethnicity was tested in univariable and multivariable logistic regression analyses predicting upstaging (pT3+/pN1) and/or upgrading (Gleason Grade Group [GGG] 4-5) at RP. RESULTS: Of 20,391 IR PCa patients, 15,050 (73.8%) were Caucasian, 2857 (14.0%) African-American, 1632 (8.0%) Hispanic/Latino and 852 (4.2%) Asian. Asian patients exhibited highest age (64 year), highest PSA (6.8 ng/ml) and highest rate of GGG3 (31.9%). African-Americans exhibited the highest percentage of positive cores at biopsy (41.7%) and the highest proportion of NCCN unfavorable risk group membership (54.6%). Conversely, Caucasians exhibited the highest proportion of cT2 stage (35.6%). In univariable analyses, Hispanic/Latinos exhibited the highest rates of upstaging/upgrading among all race/ethnicities, in both favorable and unfavorable groups, followed by Asians, Caucasians and African-Americans in that order. In multivariable analyses, Hispanic/Latino race/ethnicity represented an independent predictor of higher upstaging and/or upgrading in favorable IR PCa (odds ratio [OR] 1.27, p < 0.01), while African-American race/ethnicity represented an independent predictor of lower upstaging and/or upgrading in unfavorable IR PCa (OR 0.79, p < 0.001). CONCLUSION: Race/ethnicity predisposes to differences in clinical, as well as in pathological characteristics in IR PCa patients. Specifically, even after full statistical adjustment, Hispanic/Latinos are at higher and African-Americans are at lower risk of upstaging and/or upgrading.

YouTubeTM as a source of information on bladder pain syndrome: A contemporary analysis.

AIM: To evaluate the quality of YouTube™ videos on bladder pain syndrome (BPS) and to investigate whether they can be used as a reliable source of information. METHODS: The search term "bladder pain syndrome" was used on YouTubeTM platform. The first 100 videos were selected. Patient Education Materials Assessment Tool for audio-visual content (PEMAT A/V), Global Quality Score (GQS), Misinformation tool, and DISCERN score were used to assess videos' quality content. Pearson's test was used to assess potential correlations between variables. RESULTS: Seventy-nine videos were suitable for the analyses. The median PEMAT A/V Understandability score and PEMAT A/V Actionability score were 66.7% (interquartile range [IQR]: 46.2-100.0) and 75.0% (IQR: 37.5-100.0), respectively. According to GQS, 26 (32.9%), 32 (40.5%), 3 (3.8%), 15 (19.0%), and 3 (3.8%) videos were excellent, good, moderate, generally poor, and poor, respectively. According to Misinformation tool, of all videos, 81% (n = 64), 6.3% (n = 5), 5.1% (n = 4), 5.1% (n = 4), 2.5% (n = 2) had respectively no, very little, moderate, high, and extreme misinformation. The overall median DISCERN score ranged from 5.0 (IQR: 2.0-5.0) to 5.0 (IQR: 5.0-5.0). A positive statistically significant correlation was found between video length and PEMAT A/V Understandability (r = 0.27, p = 0.01), video length and PEMAT A/V Actionability (r = .26, p = 0.02), and video length and DISCERN Question 16 (r = 0.28, p = 0.01). CONCLUSIONS: Nowaday, the overall quality of YouTubeTM videos on BPS have been evaluated good according to PEMAT A/V, GQS, Misinformation tool, and DISCERN score. It is possible to assume that YouTubeTM may be considered as a reliable source of information on BPS.

Testicular cancer and YouTube: What do you expect from a social media platform?

OBJECTIVE: To evaluate the quality information on testicular cancer uploaded on YouTube™ videos. METHODS: YouTube™ videos were searched using "Testicular cancer" as a keyword. The Patient Education Materials Assessment Tool, the Misinformation scale, and the DISCERN tool were used to assess the quality information of YouTube™ videos on testicular cancer. RESULTS: According to the selection criteria, 121 YouTube™ videos were collected for the analysis and stratified according to uploading year (2009-2014 vs 2015-2020). According to the Patient Education Materials Assessment Tool for audio-visual content, the overall Understandability score was 60% (interquartile range 45.5-75) and the overall Actionability score was 100% (interquartile range 66.7-100). According to the Misinformation scale, the lowest median was recorded for item 6 ("Effects on fertility") and the overall median Misinformation score was 2 (interquartile range 1.3-2.8). No statistically significant differences were observed according to uploading year (all P > 0.05). Of all, only 54 (44.6%) videos mentioning treatment were subsequently analyzed. Of these videos, the overall Understandability was 71.4% (interquartile range 56.3-84.6) and the overall Actionability was 100% (interquartile range 66.7-100). The overall Misinformation score was 2.8 (interquartile range 2.2-3.5). The median DISCERN score recorded for question 16 was 5 (interquartile range 3-5). CONCLUSIONS: YouTube™ is a fast and open-access source for mass information. The overall quality of the testicular cancer contents provided is sadly unsatisfactory, in the present likewise in the past. However, YouTube™ videos mentioning treatment options showed higher quality content, than the remaining one. Nevertheless, all the videos analyzed underestimated the testicular cancer effects on fertility. Nowadays, YouTube™ cannot be recommended as a reliable source of information on testicular cancer.

Mediterranean Diet as a Shield against Male Infertility and Cancer Risk Induced by Environmental Pollutants: A Focus on Flavonoids.

The role of environmental factors in influencing health status is well documented. Heavy metals, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls, dioxins, pesticides, ultrafine particles, produced by human activities put a strain on the body's entire defense system. Therefore, together with public health measures, evidence-based individual resilience measures are necessary to mitigate cancer risk under environmental stress and to prevent reproductive dysfunction and non-communicable diseases; this is especially relevant for workers occupationally exposed to pollutants and/or populations residing in highly polluted areas. The Mediterranean diet is characterized by a high intake of fruits and vegetables rich in flavonoids, that can promote the elimination of pollutants in tissues and fluids and/or mitigate their effects through different mechanisms. In this review, we collected evidence from pre-clinical and clinical studies showing that the impairment of male fertility and gonadal development, as well as cancers of reproductive system, due to the exposure of organic and inorganic pollutants, may be counteracted by flavonoids.

Novel Insights into Autophagy and Prostate Cancer: A Comprehensive Review.

Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible.

Perioperative Red Cell Line Trend following Robot-Assisted Radical Prostatectomy for Prostate Cancer.

Background and Objective: Blood loss represents a long-standing concern of radical prostatectomy (RP). This study aimed to assess how red line cell values changed following robot-assisted radical prostatectomy (RARP) for prostate cancer (PCa). Materials and Methods: The blood panels of 453 consecutive PCa patients undergoing RARP at a single tertiary academic referral center, from September 2020 to April 2022, were reviewed. Data from 363 patients with the blood panel available for the following timeframe: within seven days before surgery, six hours after surgery, and the first three postoperative days, were analyzed. Specifically, hemoglobin (Hb, g/dL), red blood cells (RBCs, ×106/µL), and hematocrit (HCT, %) trends were collected. Results: Considering the Hb trend, the median values in the preoperative day, postoperative day (POD) 2, and POD 3 are 14.7 (interquartile range (IQR) = 13.9−15.4), 12.1 (IQR = 11.2−12.9), and 12.2 (IQR = 11.2−13.1), respectively. The ∆ between preoperative day and POD 2 is 2.5 (IQR = 1.8−3.2) (p < 0.001). Considering the RBCs trend, the median values in the preoperative day, POD 2, and POD 3 are 4.9 (IQR = 4.7−5.3), 4.1 (IQR = 3.8−4.4), and 4.1 (IQR = 3.8−4.5), respectively. The ∆ between preoperative day and POD 2 is 0.9 (IQR = 0.6−1.1) (p < 0.001). Considering the HCT trend, the median values in the preoperative day, POD 2, and POD 3 are 44.4 (IQR = 41.7−46.6), 36.4 (IQR = 33.8−38.9), and 36.1 (IQR = 33.5−38.7), respectively. The ∆ between preoperative day and POD 2 is 7.8 (IQR = 5.2−10.5) (p < 0.001). Conclusions: Overall, patients undergoing RARP experience a significant, but clinically limited, decline in red line cell values between the preoperative time and the second day post-surgery. These observations are important to provide physicians with knowledge of the expected postoperative course and, thus, to improve the quality of patient care.

Periprostatic adipose tissue promotes prostate cancer resistance to docetaxel by paracrine IGF-1 upregulation of TUBB2B beta-tubulin isoform.

Growing evidence supports the pivotal role played by periprostatic adipose tissue (PPAT) in prostate cancer (PCa) microenvironment. We investigated whether PPAT can affect response to Docetaxel (DCTX) and the mechanisms associated. Conditioned medium was collected from the in vitro differentiated adipocytes isolated from PPAT which was isolated from PCa patients, during radical prostatectomy. Drug efficacy was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide citotoxicity assay. Culture with CM of human PPAT (AdipoCM) promotes DCTX resistance in two different human prostate cancer cell lines (DU145 and PC3) and upregulated the expression of BCL-xL, BCL-2, and TUBB2B. AG1024, a well-known IGF-1 receptor inhibitor, counteracts the decreased response to DCTX observed in presence of AdipoCM and decreased TUBB2B expression, suggesting that a paracrine secretion of IGF-1 by PPAT affect DCTX response of PCa cell. Collectively, our study showed that factors secreted by PPAT elicits DCTX resistance through antiapoptotic proteins and TUBB2B upregulation in androgen independent PCa cell lines. These findings reveal the potential of novel therapeutic strategies targeting adipocyte-released factors and IGF-1 axis to overcome DCTX resistance in patients with PCa.

SARS-CoV-2 infection affects the lower urinary tract and male genital system: A systematic review.

PubMed, Scopus, and ISI Web of Knowledge databases were searched to identify studies published up to December 2020 on the involvement of urinary and male genital systems in COVID-19. Sixteen studies involving a total of 575 patients (538 males and 37 females) were included in this systematic review. The COVID-19 phase was available for 479 patients: 426 in the acute and 53 in the recovery phase. De novo lower urinary tract symptoms (LUTS) were observed in 43 patients and deterioration of pre-existing LUTS in 7. Bladder hemorrhage was observed in three patients and acute urinary retention in one. Regarding the male genital system, scrotal discomfort was observed in 8 patients, swelling in 14, pain in 16, and erythema in 1; low flow priapism was observed in 2 patients. Ultrasound examination identified acute orchitis in 10 patients, acute epididymitis in 7, and acute epididymo-orchitis in 16. A case-control study reported that patients with moderate COVID-19 show a significant reduction in sperm concertation, the total number of sperms per ejaculate, progressive motility, and complete motility. In contrast to what is known from the first studies on the subject, this review also includes subsequent studies that give evidence of the involvement of the lower urinary tract and male genital system in COVID-19.

Immune checkpoint inhibition in upper tract urothelial carcinoma.

INTRODUCTION: Immunotherapy is changing the way we think about and treat urothelial carcinoma (UC). The PD-1/PD-L1 pathway inhibition has shown robust efficacy, associated with an acceptable toxicity profile, in patients with locally advanced and metastatic unresectable disease, addressing a high decades-old unmet medical need. MATERIAL AND METHODS: Using the Pubmed database, we conducted a literature review for English written published articles up to June 2020. The highest available evidence for the immunotherapy treatment of UC with ICIs were evaluated. The leading phase one, two and three clinical trials were considered for inclusion (n = 12). Patient's data were extracted from studies depicting the UTUC subpopulation. RESULTS: Two monoclonal antibodies targeting PD-1 (pembrolizumab and nivolumab) and three to its ligand PD-L1 (atezolizumab, avelumab, and durvalumab) have obtained US FDA and EMA approval for the second-line treatment of platinum-pretreated patients, between 2016 and 2019. Atezolizumab and Pembrolizumab are even currently approved in the first-line setting for cisplatin ineligible patients, with PD-L1- positive tumor. The neoadjuvant scenario in localized high-risk disease is still evolving, with the first data available to date limited to the muscle-invasive bladder carcinoma. The management of patients with upper tract urothelial carcinoma (UTUC: renal pelvis and ureters) is complicated by the lack of specific high-level evidence, due to the rarity of the disease. No published studies addressing immunotherapy in UTUC patients only are available. The largest clinical trials aimed at UC patients, regardless of the upper or lower location of the primary tumor, have enrolled a minority of patients with UTUC, providing the data on which our current knowledge is based. However, targeted scientific efforts are needed to improve our level of care. CONCLUSIONS: This review summarizes the main currently available evidence on the use of the PD-1/PD-L1 pathway inhibition with reference to patients presenting with UTUC.

The use of Lactobacillus casei DG® prevents symptomatic episodes and reduces the antibiotic use in patients affected by chronic bacterial prostatitis: results from a phase IV study.

PURPOSE: To evaluate the efficacy of Lactobacillus paracasei CNCM I-1572 (L. casei DG®) in both prevention of symptomatic recurrences and improvement of quality of life in patients with chronic bacterial prostatitis (CBP). METHODS: Patients with CBP attending a single Urological Institution were enrolled in this phase IV study. At enrollment, all patients were treated with antibiotics in agreement with EAU guidelines and then were treated with L. casei DG® (2 capsules/day for 3 months). Clinical and microbiological analyses were carried out before (enrollment, T0) and 6 months (T2) after the treatment. Both safety and adherence to the treatment were evaluated 3 months (T1) after the enrollment. NIH Chronic Prostatitis Symptom Index (CPSI), International Prostate Symptom Score (IPSS) and Quality of Well-Being (QoL) questionnaires were used. The outcome measures were the rate of symptomatic recurrence, changes in questionnaire symptom scores and the reduction of antibiotic use. RESULTS: Eighty-four patients were included. At T2, 61 patients (72.6%) reported a clinical improvement of symptoms with a return to their clinical status before symptoms. A time dependent improvement in clinical symptoms with significant changes in NIH-CPSI, IPSS and QoL (mean difference T2 vs T0: 16.5 ± 3.58; - 11.0 ± 4.32; + 0.3 ± 0.09; p < 0.001), was reported. We recorded that L. casei DG® treatment induced a statistically significant decrease in both (p < 0.001) symptomatic recurrence [1.9/3 months vs 0.5/3 months] and antibiotic use [- 7938 UDD]. No clinically relevant adverse effects were reported. CONCLUSIONS: L. casei DG® prevents symptomatic recurrences and improves the quality of life in patients with CBP, reducing the antibiotic use.

Differences between rural and urban prostate cancer patients.

BACKGROUND: We hypothesized that the residency status (rural area [RA] vs urban clusters [UC] vs urban areas [UA]) affects stage and cancer-specific mortality (CSM) in contemporary newly diagnosed prostate cancer (PCa) patients of all stages, regardless of treatment. METHODS: Newly diagnosed PCa patients with available residency status were abstracted from the Surveillance, Epidemiology, and End Results database (2004-2016). Propensity-score (PS) matching, cumulative incidence plots, multivariate competing-risks regression (CRR) models were used. RESULTS: Of 531,468 PCa patients of all stages, 6653 (1.3%) resided in RA, 50,932 (9.6%) in UC and 473,883 (89.2%) in UA. No statistically significant or clinically meaningful differences in stage at presentation or CSM were recorded. Conversely, 10-year other cause-mortality (OCM) rates were 27.2% vs 23.7% vs 18.9% (p < 0.001) in RA vs UC vs UA patients, respectively. In CRR models, RA (subhazard ratio [SHR] 1.38; p < 0.001) and UC (SHR 1.18; p < 0.001) were independent predictors for higher OCM relative to UA. These differences remained statistically significant in fully PS-adjusted multivariate CRR models. CONCLUSION: RA, and to a lesser extent UC, PCa patients are at higher risk of OCM than UA patients. Higher OCM may indicate shorter life expectancy and should be considered in treatment decision making.

How radical prostatectomy procedures have changed over the last 10 years in Italy: a comparative analysis based on more than 1500 patients participating in the MIRROR-SIU/LUNA and the Pros-IT CNR study.

PURPOSE: Therapeutic strategies for prostate cancer (PCa) have been evolving dramatically worldwide. The current article reports on the evolution of surgical management strategies for PCa in Italy. METHODS: The data from two independent Italian multicenter projects, the MIRROR-SIU/LUNA (started in 2007, holding data of 890 patients) and the Pros-IT-CNR project (started in 2014, with data of 692 patients), were compared. Differences in patients' characteristics were evaluated. Multivariable logistic regression models were used to identify characteristics associated with robot-assisted (RA) procedure, nerve sparing (NS) approach, and lymph node dissection (LND). RESULTS: The two cohorts did not differ in terms of age and prostate-specific antigen (PSA) levels at biopsy. Patients enrolled in the Pros-IT-CNR project more frequently were submitted to RA (58.8% vs 27.6%, p < 0.001) and NS prostatectomy (58.4% vs. 52.9%, p = 0.04), but received LND less frequently (47.7% vs. 76.7%, p < 0.001), as compared to the MIRROR-SIU/LUNA patients. At multivariate logistic models, Lower Gleason Scores (GS) and PSA levels were significantly associated with RA prostatectomy in both cohorts. As for the MIRROR-SIU/LUNA data, clinical T-stage was a predictor for NS (OR = 0.07 for T3, T4) and LND (OR = 2.41 for T2) procedures. As for Pros-IT CNR data, GS ≥ (4 + 3) and positive cancer cores ≥ 50% were decisive factors both for NS (OR 0.29 and 0.30) and LND (OR 7.53 and 2.31) strategies. CONCLUSIONS: PCa management has changed over the last decade in Italian centers: RA and NS procedures without LND have become the methods of choice to treat newly medium-high risk diagnosed PCa.

Recent advances in percutaneous lithotripsy techniques.

PURPOSE OF REVIEW: To describe and critically discuss the most recent evidence regarding the percutaneous nephrolithotomy (PCNL) techniques. RECENT FINDINGS: Three-dimensional printing and virtual reality are promising tools to improve surgeon experience and operative performance. Totally ultrasound-guided PCNL is feasible and can reduce the radiological risk. Growing evidence highlights the safety and advantages of the use of miniaturized instrumentations, although some related limitations place the mini PCNL (mPCNL) in direct challenge with the retrograde intrarenal surgery. LithoClast Trilogy and ClearPetra system can improve the stone clearance. Thulium laser is a new source of energy with growing expectations and promising in-vitro results. SUMMARY: Significant advances have recently been recorded in PCNL techniques. Thulium fiber laser, LithoClast Trilogy, new suction devices, and the development of novel technologies for teaching and planning procedures may overcome mPCNL drawbacks. Further studies are needed to confirm the promising preliminary results available on the topic.

Comparison between 1973 and 2004/2016 World Health Organization grading in upper tract urothelial carcinoma treated with radical nephroureterectomy.

AIMS: The European Association of Urology guideline for upper tract urothelial carcinoma (UTUC) relies on two grading system: 1973 World Health Organization (WHO) and 2004/2016 WHO. No consensus has been made which classification should supersede the other and both are recommended in clinical practice. We hypothesized that one may be superior to the other. METHODS: Newly diagnosed non-metastatic UTUC patients treated with radical nephroureterectomy were abstracted from the Surveillance, Epidemiology, and End Results database (2010-2016). Kaplan-Meier plots and multivariable Cox regression models (CRMs) tested cancer-specific mortality (CSM), according to 1973 WHO (G1 vs. G2 vs. G3) or to 2004/2016 WHO (low-grade vs. high-grade) grading systems. Haegerty's C-index quantified accuracy. RESULTS: Of 4271 patients, according to 1973 WHO grading system, 134 (3.1%) were G1, 436 (10.2%) were G2 and 3701 (86.7%) were G3; while according to 2004/2016 WHO grading system, 508 (11.9%) were low grade vs 3763 (88.1%) high grade. In multivariable CRMs, high grade predicted higher CSM (Hazard ratio: 1.70, p < 0.001). Conversely, neither G2 (p = 0.8) nor G3 (p = 0.1) were independent predictors of worse survival. The multivariable models without consideration of either grading system were 74% accurate in predicting 5-year CSM. Accuracy increased to 76% after either addition of the 1973 WHO or 2004/2016 WHO grade. CONCLUSIONS: From a statistical standpoint, either 1973 WHO or 2004/2016 WHO grading system improves the accuracy of CSM prediction to the same extent. In consequence, other considerations such as intra- and interobserver variability may represent additional metrics to consider in deciding which grading system is better.

The Clinical Efficacy of Nitrofurantoin for Treating Uncomplicated Urinary Tract Infection in Adults: A Systematic Review of Randomized Control Trials.

OBJECTIVE: To provide an updated systematic review of randomized control trials (RCTs) to investigate the clinical and microbiological efficacy of nitrofurantoin compared to other antibiotics or placebo for treatment of uncomplicated urinary tract infections (uUTI). A secondary aim is to assess whether nitrofurantoin use is associated with increased side effects compared to other treatment regimens. SUMMARY: The review was performed according to PRISMA guidelines. We searched 4 databases for articles published from database inception to May 6, 2020: (1) PubMed electronic database of the National Library of Medicine, (2) Web of Science, (3) Embase, and (4) Cochrane Library. Nine RCTs were selected for the review. RCTs were a mixture of double-blind, single-blind, and open-label trials. The most common comparators were trimethoprim-sulfamethoxazole and fosfomycin tromethamine. Overall study quality was poor with a high risk of bias. The clinical cure rates in nitrofurantoin ranged from 51 to 94% depending on the length of follow-up, and bacteriological cure rates ranged from 61 to 92%. Overall the evidence suggests that nitrofurantoin is at least comparable with other uUTI treatments in terms of efficacy. Patients taking nitrofurantoin reported fewer side effects than other drugs and the most commonly reported were gastrointestinal and central nervous system symptoms. Key Messages: Evidence on the clinical and bacteriological efficacy of nitrofurantoin is sparse, with a lack of new data, and hampered by high risk of bias. Although no firm conclusions can be made on the current base of evidence, the studies generally suggest that nitrofurantoin is at least comparable to other common uUTI treatments in terms of clinical and bacteriological cure. More robust research with well-designed double-blinded RCTs is needed.

Higher Cancer Mortality in Rural Upper Urinary Tract Urothelial Carcinoma Patients.

OBJECTIVE: The aim of the study was to investigate differences in the stage at presentation and cancer-specific mortality (CSM) between rural area (RA) and urban area (UA) residence status in nonmetastatic upper urinary tract urothelial carcinoma (UTUC) patients. METHODS: Newly diagnosed T1-3N0M0 UTUC patients with available residence status were abstracted from the Surveillance, Epidemiology, and End Results database (2004-2016). Propensity score (PS) matching (1 RA vs. 3 UA) accounted for age (interval ≤2 years), T stage (exact matching: T1, T2, and T3), and tumor grade (exact matching: high grade, low grade/unknown). Cumulative incidence plots and multivariable competing risk regression models focused on CSM, after adjustment for other-cause mortality. RESULTS: Of 6,012 patients, 125 (2.1%) resided in RAs and 5,887 (97.9%) in UAs. RA patients were younger than UA patients (median age 72 vs. 75 years, p = 0.03). No differences were recorded in tumor location, T stage, tumor grade, or surgical treatment between RA and UA patients. After 1:3 PS matching, 125 RA patients and 375 UA patients were assessable. At 5 years of follow-up, CSM rates were 26.7 versus 15.7% according to RA versus UA, respectively. After additional multivariable adjustment for age, sex, tumor location, and surgical treatment, RA remained an independent predictor of higher CSM (hazard ratio 1.75, p = 0.02). CONCLUSIONS: Despite no differences in cancer characteristics, UTUC patients in RA are at higher risk of CSM than their UA counterparts. This suggests suboptimal care delivery and compliance as possible causes. Complex and/or rare disease should be centralized to expert centers, which are often in UAs.

Stage and cancer-specific mortality differ within specific Asian ethnic groups for upper tract urothelial carcinoma: North American population-based study.

OBJECTIVES: To examine the effect of specific Asian ethnic subgroups on stage at presentation and cancer-specific mortality in non-metastatic upper tract urothelial carcinoma among North American upper tract urothelial carcinoma Asian patients treated with radical nephroureterectomy. METHODS: We relied on the Surveillance, Epidemiology and End Results database, from 2004 to 2016. Kaplan-Meier plots and multivariable Cox regression models predicting cancer-specific mortality were used. RESULTS: Of 584 upper tract urothelial carcinoma patients, 173 (29.6%) were Chinese versus 130 (22.3%) Japanese versus 68 (11.6%) Korean versus 64 (11.0%) Filipino versus 40 (6.8%) Vietnamese versus 109 (18.7%) other. Vietnamese and Chinese patients showed the highest rates of T4 N0 M0 and/or T1-4 N1-2 M0 (25.0% and 18.5%, respectively), relative to other Asian ethnic subgroups. In Kaplan-Meier plots, Vietnamese patients showed the highest cancer-specific mortality rate. In multivariable models, Vietnamese ethnicity also independently predicted higher cancer-specific mortality (hazard ratio 2.15, P = 0.02 and hazard ratio 1.96, P = 0.03), relative to Japanese and Chinese patients. All other Asian ethnic subgroups showed similar cancer-specific mortality patterns. CONCLUSION: Vietnamese and Chinese patients are at a stage disadvantage at upper tract urothelial carcinoma diagnosis, relative to all other Asian ethnicities. After adjustment for stage, only Vietnamese patients showed a survival disadvantage relative to all other Asian ethnic subgroups. As a result, it appears that Vietnamese patients not only present at a higher upper tract urothelial carcinoma stage, but additionally appear to harbor upper tract urothelial carcinoma that progresses at a faster rate than in other Asian ethnic subgroups.

Life expectancy in metastatic prostate cancer patients according to racial/ethnic groups.

OBJECTIVES: To quantify the magnitude of differences between observed overall survival and respective, age-adjusted Social Security Administration life tables-derived life expectancy in Caucasian, African American, Hispanic/Latino and Asian metastatic prostate cancer patients. Furthermore, to test for differences in cancer-specific mortality and other-cause mortality according to race/ethnicity. METHODS: We relied on the 2004-2006 Surveillance, Epidemiology and End Results database to identify Caucasian, African American, Hispanic/Latino and Asian metastatic prostate cancer patients. Social Security Administration life tables were used to compute 10-year life expectancy for comparisons with observed overall survival. Poisson regression plots showed cancer-specific mortality relative to other-cause mortality for each race/ethnicity. RESULTS: A total of 2574 (64.2%) patients were Caucasian, 753 (18.8%) were African American, 453 (11.3%) were Hispanic/Latino and 227 (5.7%) were Asian, respectively. The median age at diagnosis was 72 years in Caucasian patients, 68 years in African American patients, 70 years in Hispanic/Latino patients and 72 years in Asian patients. Observed overall survival rates were always lower compared with respective predicted life expectancy. The magnitude of the difference between observed overall survival and predicted life expectancy at 10 years was highest in African American patients (-52.2%), followed by Caucasian patients (-48.3%), Hispanic/Latino patients (-46.1%) and Asian patients (-37.4%). African American patients showed the highest cancer-specific mortality rates (71.1%) and second-highest other-cause mortality rates (17.4% vs highest 18.4% in Caucasian patients), despite having the youngest age at diagnosis. Asian patients showed the lowest cancer-specific mortality rates (65.5%, P < 0.0001) and lowest other-cause mortality rates (13.3%, P = 0.04), despite having the oldest age at diagnosis. CONCLUSIONS: Despite having the youngest age at diagnosis, African American patients show the least favorable survival profile in metastatic prostate cancer. Conversely, Asian patients show the most favorable survival profile in metastatic prostate cancer, despite having the oldest age at diagnosis.