Detection of Significant Prostate Cancer Using Target Saturation in Transperineal Magnetic Resonance Imaging/Transrectal Ultrasonography-fusion Biopsy

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) and targeted biopsies (TBs) facilitate accurate detection of significant prostate cancer (sPC). However, it remains unclear how many cores should be applied per target. OBJECTIVE: To assess sPC detection rates of two different target-dependent magnetic resonance imaging (MRI)/transrectal ultrasonography (TRUS)-fusion biopsy approaches (TB and target saturation [TS]) compared with extended systematic biopsies (SBs). DESIGN, SETTING, AND PARTICIPANTS: Retrospective single-centre outcome of transperineal MRI/TRUS-fusion biopsies of 213 men was evaluated. All men underwent TB with a median of four cores per MRI lesion, followed by a median of 24 SBs, performed by experienced urologists. Cancer and sPC (International Society of Urological Pathology grade group ≥2) detection rates were analysed. TB was compared with SB and TS, with nine cores per target, calculated by the Ginsburg scheme and using individual cores of the lesion and its "penumbra". OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cancer detection rates were calculated for TS, TB, and SB at both lesion and patient level. Combination of SB + TB served as a reference. Statistical differences in prostate cancer (PC) detection between groups were calculated using McNemar's tests with confidence intervals. RESULTS AND LIMITATIONS: TS detected 99% of 134 sPC lesions, which was significantly higher than the detection by TB (87%, p = 0.001) and SB (82%, p < 0.001). SB detected significantly more of the 72 low-risk PC lesions than TB (99% vs 68%, p < 0.001) and 10% (p = 0.15) more than that detected by TS. At a per-patient level, 99% of men harbouring sPC were detected by TS. This was significantly higher than that by TB and SB (89%, p = 0.03 and 81%, p = 0.001, respectively). Limitations include limited generalisability, as a transperineal biopsy route was used. CONCLUSIONS: TS detected significantly more cases of sPC than TB and extended SB. Given that both 99% of sPC lesions and men harbouring sPC were identified by TS, the results suggest that this approach allows to omit SB cores without compromising sPC detection. PATIENT SUMMARY: Target saturation of magnetic resonance imaging-suspicious prostate lesions provides excellent cancer detection and finds fewer low-risk tumours than the current gold standard combination of targeted and systematic biopsies

High-soluble CGA levels are associated with poor survival in bladder cancer

Recently, a neuroendocrine-like molecular subtype has been discovered in muscle-invasive urothelial bladder cancer (BC). Chromogranin A (CGA) is a widely used tissue and serum marker in neuroendocrine tumors. Our aim was to evaluate serum CGA (sCGA) concentrations and their associations with clinical and follow-up data in BC and renal cell carcinoma (RCC). sCGA concentrations were analyzed in the following cohorts: (1) BC training set (n = 188), (2) BC validation set (n = 125), (3) RCC patients (n = 77), (4) healthy controls (n = 97). CGA immunohistochemistry and RT-qPCR analyses were performed in 20 selected FFPE and 29 frozen BC tissue samples. Acquired data were correlated with clinicopathological parameters including comorbidities with known effect on sCGA as well as with patients’ follow-up data. sCGA levels were significantly higher in BC but not in RCC patients compared to healthy controls. High sCGA levels were independently associated with poor overall and disease-specific survival both in the BC training (P < 0.001, P = 0.002) and validation set (P = 0.009, P = 0.017). sCGA levels were inversely correlated with glomerulus filtrating rate (GFR) and linearly correlated with creatinine clearance and urea concentrations. These correlations were not related to the prognostic value of sCGA. Tissue CGA levels were low to absent independently of sCGA concentrations. Our results demonstrate elevated levels and an independent prognostic value for sCGA in BC but not in RCC. Despite the significant correlation between sCGA and GFR, the prognostic relevance of sCGA seems not related to impaired renal function or other comorbidities

Непрямое сравнение эффективности и безопасности апалутамида и даролутамида для лечения неметастатического кастрационнорезистентного рака предстательной железы по результатам двух независимых исследований с поправкой на разницу между популяциями пациентов

.Введение. Апалутамид и даролутамид являются ингибиторами андрогенных рецепторов нового поколения, которые продемонстрировали превосходную эффективность у пациентов с неметастатическим кастрационно-резистентным раком предстательной железы, получающих андрогендепривационную терапию (АДТ). На сегодняшний день нет исследований по прямому сравнению этих 2 препаратов.Цель исследования – непрямое сравнение эффективности и переносимости апалутамида и даролутамида.Материалы и методы. Был применен метод согласованного скорректированного непрямого сравнения (matchingadjusted indirect comparison, MAIC) данных рандомизированного плацебо-контролируемого исследования III фазы SPARTAN (апалутамид + АДТ), которые были уравновешены по основным исходным клиническим параметрам, с опубликованными обобщенными данными исследования ARAMIS (даролутамид + АДТ) для их сопоставления. Для оценки всех конечных точек эффективности, включая выживаемость без метастазирования, повышение уровня простатического специфического антигена (ПСА), выживаемость без прогрессирования, а также общую выживаемость, были рассчитаны отношения рисков (ОР) и 95 % доверительные интервалы (ДИ). Для оценки конечных точек по безопасности (частота нежелательных явлений и серьезных нежелательных явлений) рассчитывали отношения шансов.Результаты. Перед уравновешиванием данных в исследованиях SPARTAN и ARAMIS наблюдались значимые различия по уровню ПСА (медиана 7,8 нг/мл против 9,2 нг/мл), числу пациентов со статусом 1 по шкале Eastern Cooperative Oncology Group (23 % против 31 %), частоте использования препаратов для модификации костной ткани (10 % против 4 %), медиане времени с момента установления первичного диагноза (94,9 мес против 85,4 мес) и числу пациентов из США (35 % против 12 %) и Европы (50 % против 64 %). После уравновешивания данных (n = 455) мы установили, что режим, включающий апалутамид + АДТ, с высокой долей вероятности более эффективен, чем даролутамид + АДТ, по выживаемости без метастазирования (98,3 %; ОР 0,70; 95 % ДИ 0,51–0,98), повышениюуровня ПСА (~100 %; ОР 0,46; 95 % ДИ 0,33–0,64) и выживаемости без прогрессирования (93,2 %; ОР 0,79; 95 % ДИ 0,59–1,08). Показатели общей выживаемости и переносимости не различались значительно при сравнении групп апалутамид + АДТ и даролутамид + АДТ.Заключение. Результаты анализа данных 2 важнейших исследований III фазы по неметастатическому кастрационно-резистентному раку предстательной железы с помощью метода MAIC указывают на то, что апалутамид + АДТ является более эффективной схемой лечения, чем даролутамид + АДТ, по показателям выживаемости без прогрессирования и повышению уровня ПСА, в то время как общая выживаемость и профиль безопасности этих 2 режимов не различаются.

MRI-targeted or standard biopsy for prostate-cancer diagnosis

Background Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography-guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited. Methods In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography-guided biopsy. Men in the MRI-targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10-to-12-core, transrectal ultrasonography-guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. Results A total of 500 men underwent randomization. In the MRI-targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI-targeted biopsy group, as compared with 64 of 248 (26%) in the standard-biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI-targeted biopsy group than in the standard-biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, -13 percentage points; 95% CI, -19 to -7; P&lt;0.001). Conclusions The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027 .)

To defer or not to defer? A German longitudinal multicentric assessment of clinical practice in urology during the COVID-19 pandemic

Introduction After the outbreak of COVID-19 unprecedented changes in the healthcare systems worldwide were necessary resulting in a reduction of urological capacities with postponements of consultations and surgeries. Material and methods An email was sent to 66 urological hospitals with focus on robotic surgery (RS) including a link to a questionnaire (e.g. bed/staff capacity, surgical caseload, protection measures during RS) that covered three time points: a representative baseline week prior to COVID-19, the week of March 16th-22nd and April 20th-26th 2020. The results were evaluated using descriptive analyses. Results 27 out of 66 questionnaires were analyzed (response rate: 41%). We found a decrease of 11% in hospital beds and 25% in OR capacity with equal reductions for endourological, open and robotic procedures. Primary surgical treatment of urolithiasis and benign prostate syndrome (BPS) but also of testicular and penile cancer dropped by at least 50% while the decrease of surgeries for prostate, renal and urothelial cancer (TUR-B and cystectomies) ranged from 15 to 37%. The use of personal protection equipment (PPE), screening of staff and patients and protection during RS was unevenly distributed in the different centers\u2013however, the number of COVID-19 patients and urologists did not reach double digits. Conclusion The German urological landscape has changed since the outbreak of COVID-19 with a significant shift of high priority surgeries but also continuation of elective surgical treatments. While screening and staff protection is employed heterogeneously, the number of infected German urologists stays low

Transperineal prostate biopsies for diagnosis of prostate cancer are well tolerated: a prospective study using patient-reported outcome measures

We aimed to determine short-term patient-reported outcomes in men having general anesthetic transperineal (TP) prostate biopsies. A prospective cohort study was performed in men having a diagnostic TP biopsy. This was done using a validated and adapted questionnaire immediately post-biopsy and at follow-up of between 7 and 14 days across three tertiary referral hospitals with a response rate of 51.6%. Immediately after biopsy 43/201 (21.4%) of men felt light-headed, syncopal, or suffered syncope. Fifty-three percent of men felt discomfort after biopsy (with 95% scoring <5 in a 0-10 scale). Twelve out of 196 men (6.1%) felt pain immediately after the procedure. Despite a high incidence of symptoms (e.g., up to 75% had some hematuria, 47% suffered some pain), it was not a moderate or serious problem for most, apart from hemoejaculate which 31 men suffered. Eleven men needed catheterization (5.5%). There were no inpatient admissions due to complications (hematuria, sepsis). On repeat questioning at a later time point, only 25/199 (12.6%) of men said repeat biopsy would be a significant problem despite a significant and marked reduction in erectile function after the procedure. From this study, we conclude that TP biopsy is well tolerated with similar side effect profiles and attitudes of men to repeat biopsy to men having TRUS biopsies. These data allow informed counseling of men prior to TP biopsy and a benchmark for tolerability with local anesthetic TP biopsies being developed for clinical use.Boris Hadaschik received funding from the German Research Foundation and the European Foundation for Urology. Karan Wadhwa is sponsored by a Medical Research Council Research Training Fellowship. No other funding was received for this work

Genome-Wide Profiling of MicroRNAs in Adipose Mesenchymal Stem Cell Differentiation and Mouse Models of Obesity

In recent years, there has been accumulating evidence that microRNAs are key regulator molecules of gene expression. The cellular processes that are regulated by microRNAs include e.g. cell proliferation, programmed cell death and cell differentiation. Adipocyte differentiation is a highly regulated cellular process for which several important regulating factors have been discovered, but still not all are known to fully understand the underlying mechanisms. In the present study, we analyzed the expression of 597 microRNAs during the differentiation of mouse mesenchymal stem cells into terminally differentiated adipocytes by real-time RT-PCR. In total, 66 miRNAs were differentially expressed in mesenchymal stem cell-derived adipocytes compared to the undifferentiated progenitor cells. To further study the regulation of these 66 miRNAs in white adipose tissue in vivo and their dependence on PPARγ activity, mouse models of genetically or diet induced obesity as well as a mouse line expressing a dominant negative PPARγ mutant were employed

Experimental rat bladder urothelial cell carcinoma models

Bladder cancer is a major public health problem. Currently available therapeutic options seem to be unable to prevent bladder cancer recurrence and progression. To enable preclinical testing of new intravesical therapeutic agents, a suitable bladder tumor model that resembles human disease is highly desirable. The aim of this topic paper was to discuss the problems associated with current in vivo animal bladder tumor models, focusing on the orthotopic syngeneic rat bladder tumor model. In the second part of the paper the development of a potential new orthotopic rat bladder tumor model is described