Utilization of sperm cryopreservation in patients with testicular cancer.

PURPOSE: We assessed factors that affect the utilization of sperm cryopreservation before 2021, when patients covered expenses, and the influence on quality of life. METHODS: Between 2011 and 2021, testicular cancer survivors (TCS) at our clinic completed a questionnaire, including EORTC QLQ-TC26, covering sperm cryopreservation, sociodemographic details, post-treatment births, and artificial insemination. RESULTS: After 5.7 ± 3.0 years, 279 participants (64%) responded to the questionnaire. Among them, 33% (91/279) of testicular cancer survivors chose sperm cryopreservation prior to treatment, with 11% (10/91) using it for insemination. Conversely, 2% (3/188) without cryopreservation reported unfulfilled desire to have children. Univariate analysis showed TCS with cryopreservation were younger (30.6 ± 7.1 (35 (21-59)) vs. 42.4 ± 10.9 (48 (22-81)) years; p = 0.001), had a lower BMI (24.2 ± 3.3 vs. 26.6 ± 4.6 kg/m2; p = 0.009) and a lower Charlson Score (> 3: 36% vs. 60%; p < 0.001). Multivariate analysis revealed older age (≥ 37 years: OR 13.1 (5.5-31.2), p < 0.001) and lower education (middle school or less: OR 3.3 (1.6-6.9), p = 0.001) as independent factors associated with not undergoing cryopreservation. Regarding quality of life, multivariate analysis identified a lower infertility anxiety score (OR 4.3 (2.0-9.0), p < 0.001) and higher age (≥ 44 years: OR 5.4 (2.6-11.3); p < 0.001) as predictors for the absence of prior cryopreservation. CONCLUSIONS: Age and education seem to impact the choice of undergoing paid sperm cryopreservation. Urologists should inform testicular cancer patients about costs and coverage. Importantly, the occurrence of unmet desires for parenthood is minimal among those who forego cryopreservation.

Research Protocol for an Observational Health Data Analysis on the Adverse Events of Systemic Treatment in Patients with Metastatic Hormone-sensitive Prostate Cancer: Big Data Analytics Using the PIONEER Platform.

Combination therapies in metastatic hormone-sensitive prostate cancer (mHSPC), which include the addition of an androgen receptor signaling inhibitor and/or docetaxel to androgen deprivation therapy, have been a game changer in the management of this disease stage. However, these therapies come with their fair share of toxicities and side effects. The goal of this observational study is to report drug-related adverse events (AEs), which are correlated with systemic combination therapies for mHSPC. Determining the optimal treatment option requires large cohorts to estimate the tolerability and AEs of these combination therapies in "real-life" patients with mHSPC, as provided in this study. We use a network of databases that includes population-based registries, electronic health records, and insurance claims, containing the overall target population and subgroups of patients defined by unique certain characteristics, demographics, and comorbidities, to compute the incidence of common AEs associated with systemic therapies in the setting of mHSPC. These data sources are standardised using the Observational Medical Outcomes Partnership Common Data Model. We perform the descriptive statistics as well as calculate the AE incidence rate separately for each treatment group, stratified by age groups and index year. The time until the first event is estimated using the Kaplan-Meier method within each age group. In the case of episodic events, the anticipated mean cumulative counts of events are calculated. Our study will allow clinicians to tailor optimal therapies for mHSPC patients, and they will serve as a basis for comparative method studies.

[Metastasis-directed therapy in prostate cancer]. / Metastasen-gerichtete Strahlentherapie beim Prostatakarzinom.

BACKGROUND: Metastasis-directed therapy (MDT) in oligometastatic prostate cancer (omHSPC) is playing an increasingly important role in therapy with the aim of delaying disease progression, the start of systemic treatment or switching systemic treatment to improve the patient's overall prognosis. Molecular imaging as prostate-specific membrane antigen positron emission tomography (PSMA-PET) imaging allows metastases to be detected with a higher sensitivity and specificity. This means that they can be detected early and made accessible for treatment. RESULTS: The standard therapy for oligo-mHSPC is androgen deprivation (ADT), which is supplemented by novel hormonal therapeutics (NHT). A few small prospective trials have shown an extension of the ADT-free interval and progression-free survival (PFS), particularly in metachronous oligo-mHSPC, by MDT, usually radiotherapy. Additional ADT can further extend the PFS in particular. There are hardly any prospective data for synchronous oligo-mHSPC. CONCLUSION: Despite the currently still poor evidence, MDT is playing an increasingly important role. The still unclear definition of oligometastasis and the large number of influencing factors make it difficult to compare current data. Large multicenter prospective data are still pending. It is also important to clarify the effect of limited ADT in combination with NHT in the treatment of synchronous and metachronous oligo-mHSPC with MDT. In synchronous oligo-mHSPC in particular, further benefit of additional local therapy of the primary in combination with MDT should also be investigated.

A reliable transcriptomic risk-score applicable to formalin-fixed paraffin-embedded biopsies improves outcome prediction in localized prostate cancer.

BACKGROUND: Clinical manifestation of prostate cancer (PCa) is highly variable. Aggressive tumors require radical treatment while clinically non-significant ones may be suitable for active surveillance. We previously developed the prognostic ProstaTrend RNA signature based on transcriptome-wide microarray and RNA-sequencing (RNA-Seq) analyses, primarily of prostatectomy specimens. An RNA-Seq study of formalin-fixed paraffin-embedded (FFPE) tumor biopsies has now allowed us to use this test as a basis for the development of a novel test that is applicable to FFPE biopsies as a tool for early routine PCa diagnostics. METHODS: All patients of the FFPE biopsy cohort were treated by radical prostatectomy and median follow-up for biochemical recurrence (BCR) was 9 years. Based on the transcriptome data of 176 FFPE biopsies, we filtered ProstaTrend for genes susceptible to FFPE-associated degradation via regression analysis. ProstaTrend was additionally restricted to genes with concordant prognostic effects in the RNA-Seq TCGA prostate adenocarcinoma (PRAD) cohort to ensure robust and broad applicability. The prognostic relevance of the refined Transcriptomic Risk Score (TRS) was analyzed by Kaplan-Meier curves and Cox-regression models in our FFPE-biopsy cohort and 9 other public datasets from PCa patients with BCR as primary endpoint. In addition, we developed a prostate single-cell atlas of 41 PCa patients from 5 publicly available studies to analyze gene expression of ProstaTrend genes in different cell compartments. RESULTS: Validation of the TRS using the original ProstaTrend signature in the cohort of FFPE biopsies revealed a relevant impact of FFPE-associated degradation on gene expression and consequently no significant association with prognosis (Cox-regression, p-value > 0.05) in FFPE tissue. However, the TRS based on the new version of the ProstaTrend-ffpe signature, which included 204 genes (of originally 1396 genes), was significantly associated with BCR in the FFPE biopsy cohort (Cox-regression p-value < 0.001) and retained prognostic relevance when adjusted for Gleason Grade Groups. We confirmed a significant association with BCR in 9 independent cohorts including 1109 patients. Comparison of the prognostic performance of the TRS with 17 other prognostically relevant PCa panels revealed that ProstaTrend-ffpe was among the best-ranked panels. We generated a PCa cell atlas to associate ProstaTrend genes with cell lineages or cell types. Tumor-specific luminal cells have a significantly higher TRS than normal luminal cells in all analyzed datasets. In addition, TRS of epithelial and luminal cells was correlated with increased Gleason score in 3 studies. CONCLUSIONS: We developed a prognostic gene-expression signature for PCa that can be applied to FFPE biopsies and may be suitable to support clinical decision-making.

PI-RADS upgrading as the strongest predictor for the presence of clinically significant prostate cancer in patients with initial PI-RADS-3 lesions.

PURPOSE: Unclear lesions on multiparametric magnetic resonance tomography (mpMRI) are challenging for the indication of biopsy in patients with clinical suspicion of prostate cancer (PCa). The aim of this study is the validation of the detection rate of clinically significant PCa (csPCa) in patients with PI-RADS 3 findings and to determine the appropriate follow-up strategy. METHODS: In this retrospective single-center study, patients with maximum PI-RADS 3 lesions underwent targeted MRI/ultrasound-fusion biopsy (tPbx) combined with systematic 12-core biopsy (sPbx) and follow-up mpMRI with further control biopsy. We assessed the evolution of MRI findings (PI-RADS, volume of the lesion), clinical parameters and histopathology in follow-up MRI and biopsies. The primary objective is the detection rate of csPCa, defined as ISUP ≥ 2 findings. RESULTS: A total of 126 patients (median PSA 6.65 ng/ml; median PSA-density (PSAD) 0.13 ng/ml2) were included. The initial biopsy identified low-risk PCa in 24 cases (19%). During follow-up biopsy, 22.2% of patients showed PI-RADS upgrading (PI-RADS > 3), and 29 patients (23%) exhibited a tumor upgrading. Patients with PI-RADS upgrading had a higher risk of csPCa compared to those without PI-RADS upgrading (42.9% vs. 9.18%, p < 0.05). PI-RADS upgrading was identified as an independent predictor for csPCa in follow-up biopsy (OR 16.20; 95% CI 1.17-224.60; p = 0.038). CONCLUSION: Patients with stable PI-RADS 3 findings may not require a follow-up biopsy. Instead, it is advisable to schedule an MRI, considering that PI-RADS upgrading serves as an independent predictor for csPCa.

Do we need MRI in all biopsy naïve patients? A multicenter cohort analysis.

PURPOSE: The combined approach (CB) of magnetic resonance imaging (MRI)-guided biopsy (TB) and systematic biopsy (SB) is strongly recommended based on numerous studies in biopsy naïve men with suspicion of clinically significant prostate cancer (csPCA). However, the unbalanced accessibility of MRI, challenges related to reimbursement and the scarcity of specialized medical practitioners continue to impede a widespread implementation. Therefore, our objective was to determine a subset of men that could undergo SB without an increased risk of underdiagnosis at reduced expenses. METHODS: A multicenter analysis of 2714 men with confirmed PCA and suspicious MRI who underwent CB were enrolled. Cancer detection rates were compared between the different biopsy routes SB, TB and CB using McNemar paired test. Additionally, Gleason grade up- and down-grading was determined. RESULTS: CB detected more csPCA than TB and SB (p < 0.001), irrespective of MRI findings or biopsy route (transperineal vs. transrectal). Thereby, single biopsy approaches misgraded > 50% of csPCA. TB showed higher diagnostic efficiency, defined as csPCA detection per biopsy core than CB and SB (p < 0.001). For patients with abnormal DRE and PSA levels > 12.5 ng/ml, PSAD > 0.35 ng/ml/cm3, or > 75 years, SB and CB showed similar csPCA detection rates. CONCLUSION: Conducting CB provides the highest level of diagnostic certainty and minimizes the risk of underdiagnosis in almost all biopsy-naive men. However, in patients with suspicious DRE and high PSA levels, PSAD, or advanced age solely using SB leads to similar csPCA detection rates. Thus, a reduced biopsy protocol may be considered for these men in case resources are limited.

Identification of genomic drivers for the therapeutic response of Cabozantinib in patients with metastatic renal cell carcinoma.

PURPOSE: Cabozantinib (CAB) as monotherapy or in combination with immune checkpoint inhibitors is used for systemic treatment of metastatic renal cell carcinoma (mRCC). However, little is known about predictors of treatment response to CAB. For this reason, known genomic drivers were examined to identify potential predictors of treatment response with CAB. METHODS: Twenty mRCC patients receiving monotherapy (≥ first-line) with CAB were prospectively included. DNA was extracted from archived primary tumors or metastatic tissue. Targeted DNA sequencing was performed using a gene panel including 328 genes (QIAseq Targeted DNA V3 Panel, Qiagen). The variant evaluation was performed using Varsome. The endpoints were treatment-failure-free-survival (TFFS) to CAB. RESULTS: 26% of patients received systemic RCC treatment as the primary option. Six patients were treated with CAB in first-line (1L) and 12 patients in ≥ 2L. The median follow-up after initiation of systemic treatment was 26.7 months (mo). The PBRM1 (7 alleles), SETD2 (7 alleles), VHL (11 alleles), and CHEK2 (14 alleles) genes were most frequently altered. The median time to TFFS was 10.5 mo (95% confidence interval (CI) 6.2-14.7 mo). There was a longer treatment response to CAB in patients with alterations of the SETD2 gene (SETD2 alteration median TFFS not reached vs. no SETD2 alterations 8.4 mo (95% CI 5.2-11.6 mo); p = 0.024). CONCLUSION: Pathogenic variant genes may indicate treatment response to systemic therapy in mRCC. Patients with alterations of the SETD2 gene show longer responses to CAB treatment.

The Role of Multiparametric MRI (mpMRI) in the Prediction of Adverse Prostate Cancer Pathology in Radical Prostatectomy Specimen.

INTRODUCTION: Prostate cancer (PCa) risk stratification is essential in guiding therapeutic decision. Multiparametric magnetic resonance tomography (mpMRI) holds promise in the prediction of adverse pathologies (AP) after prostatectomy (RP). This study aims to identify clinical and imaging markers in the prediction of adverse pathology. METHODS: Patients with PCa, diagnosed by targeted biopsy after mpMRI and undergoing RP, were included. The predictive accuracy of mpMRI for extraprostatic extension (ECE), seminal vesicle infiltration (SVI), and lymph node positivity was calculated from the final histopathology. RESULTS: 846 patients were involved. Independent risk parameters include imaging findings such as ECE (OR 3.12), SVI (OR 2.55), and PI-RADS scoring (4: OR 2.01 and 5: OR 4.34). mpMRI parameters such as ECE, SVI, and lymph node metastases showed a high prognostic accuracy (73.28% vs. 95.35% vs. 93.38%) with moderate sensitivity compared to the final histopathology. The ROC analysis of our combined scoring system (D'Amico classification, PSA density, and MRI risk factors) improves the prediction of adverse pathology (AUC: 0.73 vs. 0.69). CONCLUSION: Our study supports the use of mpMRI for comprehensive pretreatment risk assessment in PCa. Due to the high accuracy of factors like ECE, SVI, and PI-RADS scoring, utilizing mpMRI data enabled accurate prediction of unfavorable pathology after RP.

ALDH1A1 drives prostate cancer metastases and radioresistance by interplay with AR- and RAR-dependent transcription.

Rationale: Current therapies for metastatic osseous disease frequently fail to provide a durable treatment response. To date, there are only limited therapeutic options for metastatic prostate cancer, the mechanisms that drive the survival of metastasis-initiating cells are poorly characterized, and reliable prognostic markers are missing. A high aldehyde dehydrogenase (ALDH) activity has been long considered a marker of cancer stem cells (CSC). Our study characterized a differential role of ALDH1A1 and ALDH1A3 genes as regulators of prostate cancer progression and metastatic growth. Methods: By genetic silencing of ALDH1A1 and ALDH1A3 in vitro, in xenografted zebrafish and murine models, and by comparative immunohistochemical analyses of benign, primary tumor, and metastatic specimens from patients with prostate cancer, we demonstrated that ALDH1A1 and ALDH1A3 maintain the CSC phenotype and radioresistance and regulate bone metastasis-initiating cells. We have validated ALDH1A1 and ALDH1A3 as potential biomarkers of clinical outcomes in the independent cohorts of patients with PCa. Furthermore, by RNAseq, chromatin immunoprecipitation (ChIP), and biostatistics analyses, we suggested the molecular mechanisms explaining the role of ALDH1A1 in PCa progression. Results: We found that aldehyde dehydrogenase protein ALDH1A1 positively regulates tumor cell survival in circulation, extravasation, and metastatic dissemination, whereas ALDH1A3 plays the opposite role. ALDH1A1 and ALDH1A3 are differentially expressed in metastatic tumors of patients with prostate cancer, and their expression levels oppositely correlate with clinical outcomes. Prostate cancer progression is associated with the increasing interplay of ALDH1A1 with androgen receptor (AR) and retinoid receptor (RAR) transcriptional programs. Polo-like kinase 3 (PLK3) was identified as a transcriptional target oppositely regulated by ALDH1A1 and ALDH1A3 genes in RAR and AR-dependent manner. PLK3 contributes to the control of prostate cancer cell proliferation, migration, DNA repair, and radioresistance. ALDH1A1 gain in prostate cancer bone metastases is associated with high PLK3 expression. Conclusion: This report provides the first evidence that ALDH1A1 and PLK3 could serve as biomarkers to predict metastatic dissemination and radiotherapy resistance in patients with prostate cancer and could be potential therapeutic targets to eliminate metastasis-initiating and radioresistant tumor cell populations.

Follow-up of vascular-targeted photodynamic therapy in a real-world setting.

PURPOSE: Vascular-targeted photodynamic therapy (VTP) is an approved treatment option for unilateral low-risk prostate cancer (PCa). METHODS: Patients with unilateral low- or intermediate-risk PCa undergoing hemiablation by VTP were evaluated in a real-world setting. Oncological outcome after VTP was measured by MRI-based re-biopsy at 12 and 24 months. Functional outcome after 1 year was investigated by IIEF-5 and IPSS questionnaires. Progression was defined as the evidence3 of ISUP ≥ 2 PCa. RESULTS: At any control biopsy (n = 46) after VTP, only 37% of patients showed no evidence of PCa. Recurrence-free survival was 20 months (95% CI 4.9-45.5) and progression-free survival was 38.5 months (95% CI 33.5-43.6 months). In-field and out-field recurrent PCa occurs in 37% (55% ISUP ≥ 2 PCa) and 35% (56% ISUP ≥ 2 PCa). Seventy-nine percent of patients preserved erectile function, respectively. Ten percent of patients presented long-term bladder outlet obstruction. None of the patients presented incontinence. CONCLUSION: Due to the high-recurrence in- and out-field recurrence rate in a mainly low-risk prostate cancer cohort, VTP has to be regarded critically as a therapy option in these patients. Pre-interventional diagnostic evaluation is the main issue before focal therapy to reduce the risk of tumor recurrence and progression.

Emergency treatment of symptomatic ureteral calculi: predictors of prolonged hospital stay.

PURPOSE: To assess differences in the length of hospital stay (LOS) in patients who present emergently versus electively for a symptomatic ureteral stone and to explore underlying risk factors. METHODS: Billing data were analyzed from patients with symptomatic ureteral calculi at our department from 2010 to 2021. Statistical analysis (U test, logistic regression) was performed. RESULTS: 2274 patients (72% male, 28% female) with ureteral stones were analyzed (mean age of 52.9y). 1578 patients (69.4%) presented in an emergency setting and 696 patients (30.6%) electively. Arterial hypertension was seen in 31%, diabetes mellitus in 11% and hyperuricemia in 5% of the whole cohort. 46.5% of emergency patients were desobstructed (DJ/PCN), 35.4% underwent emergency ureteroscopy (URS), 13.4% had spontaneous passage (SP), and 4.8% underwent emergency shock wave lithotripsy (SWL). Of the electively treated patients, 58.6% underwent URS, 21.3% SWL, 18.5% DJ/PCN, and 1.6% had SP. Emergency stone treatment was associated with a significantly longer LOS when compared to primary desobstruction for patients admitted emergently. Also, LOS was significantly longer for each intervention of stone treatment in emergency patients vs. electively treated patients. Arterial hypertension was associated with a 1.8-fold increased risk of a hospital stay longer than 3 days, irrespective of hospital admission mode, whereas metabolic disorders did not influence LOS in this cohort. CONCLUSION: For emergency patients in contrast to the electively treated patients, the type of procedure had a significant impact on the length of hospital stay. Arterial hypertension is an independent significant risk factor for prolonged hospital stay.

[Digitalization in urology-challenge and opportunity]. / Digitalisierung in der Urologie ­ Herausforderung und Chance.

Digitalization is changing medicine. In Germany these changes are not highly accepted yet. Medical pathways should be supported and become safer by digital transformation. Furthermore, artificial intelligence (AI) applications are increasingly used in medicine. Only time will tell whether these will decrease the workload and make patient treatment easier, while increasing precision and individualization.. Urology must accept the upcoming new challenges. This can best be done by participating in the development.

Retroperitoneal lymph node dissection for testicular cancer is a demanding procedure: detailed real-life data of complications and additional surgical procedures in 295 cases.

PURPOSE: Retroperitoneal lymph node dissection (RPLND) for germ cell tumours is a challenging procedure that may present relevant complications. The purpose was to analyse postoperative complications and identify risk factors for major complications. METHODS: This is a retrospective unicentric analysis of a large cohort of 295 RPLNDs from 1992 to 2020. Early complications (30 days) and late complications (31-180 days) were classified according to the Clavien‒Dindo classification. The influence of surgical, patient-specific, and tumour-specific parameters on grade III-V complications was analysed in univariate and multivariate logistic regression models. RESULTS: A total of 232 were postchemotherapy RPLNDs, and 63 were primary RPLNDs. Early postoperative complications were found to be grades I-II in 58.6% (173/295), grades III-IV in 9.8% (29/295), and grade V in 0.3% (1/295). In 20% (58/295), additional surgical procedures were needed. Grade III-V complications were associated with ≥ 4 cycles of preoperative chemotherapy (OR 3.7 (1.5-8.9); p = 0.004), RPLND specimen (nonseminoma or immature teratoma) (OR 3.1 (1.4-6.6); p = 0.005), transfusions (OR 2.4 (1.1-5.4); p = 0.03), salvage RPLND (OR 4.1 (1.8-9.3); p < 0.001), and preoperatively elevated AFP (OR 5 (2.2-11.7); p < 0.001). In multivariate analysis, the only independent predictor for grade III-V complications was preoperative AFP elevation (OR 3.3 (1.2-9.2); p = 0.02). Limitations include the retrospective study design. CONCLUSIONS: Our results demonstrate that RPLND is a demanding surgical procedure. Patients with a complex tumour history have a higher risk of complications. We recommend treatment of these complex cases in high-volume centres.

Insufficient utilization of care in male incontinence surgery: health care reality in Germany from 2006 to 2020 and a systematic review of the international literature.

PURPOSE: Data suggest that the utilization of care in male incontinence surgery (MIS) is insufficient. The aim of this study was to analyse the utilization of care in MIS from 2006 to 2020 in Germany, relate this use to the number of radical prostatectomies (RP) and provide a systematic review of the international literature. METHODS: We analysed OPS codes using nationwide German billing data and hospitals' quality reports from 2006 to 2020. A systematic review was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). RESULTS: MIS increased by + 68% from 2006 to 2011 (1843-3125; p = 0.009) but decreased by - 42% from 2011 to 2019 (3104-1799; p < 0.001). In 2020, only 1435 MISs were performed. In contrast, RP increased from 2014 to 2019 by 33% (20,760-27,509; p < 0.001). From 2012 to 2019, the number of artificial urinary sphincters (AUSs) changed minimally (- 12%; 1291-1136; p = 0.02). Sling/sling systems showed a decrease from 2011 to 2019 (- 68% 1632-523; p < 0.001). In 2019, 63% of patients received an AUS, 29% sling/sling systems, 6% paraurethral injections, and 2% other interventions. In 2019, few high-volume clinics [n = 27 (13%)] performed 55% of all AUS implantations, and few high-volume clinics [n = 10 (8%)] implanted 49% of retropubic slings. CONCLUSION: MIS have exhibited a relevant decrease since 2011 despite the increase in RP numbers in Germany, indicating the insufficient utilization of care in MIS. The systematic review shows also an international deficit in the utilization of care in MIS.

Characterization and evaluation of gene fusions as a measure of genetic instability and disease prognosis in prostate cancer.

BACKGROUND: Prostate cancer (PCa) is one of the most prevalent cancers worldwide. The clinical manifestations and molecular characteristics of PCa are highly variable. Aggressive types require radical treatment, whereas indolent ones may be suitable for active surveillance or organ-preserving focal therapies. Patient stratification by clinical or pathological risk categories still lacks sufficient precision. Incorporating molecular biomarkers, such as transcriptome-wide expression signatures, improves patient stratification but so far excludes chromosomal rearrangements. In this study, we investigated gene fusions in PCa, characterized potential novel candidates, and explored their role as prognostic markers for PCa progression. METHODS: We analyzed 630 patients in four cohorts with varying traits regarding sequencing protocols, sample conservation, and PCa risk group. The datasets included transcriptome-wide expression and matched clinical follow-up data to detect and characterize gene fusions in PCa. With the fusion calling software Arriba, we computationally predicted gene fusions. Following detection, we annotated the gene fusions using published databases for gene fusions in cancer. To relate the occurrence of gene fusions to Gleason Grading Groups and disease prognosis, we performed survival analyses using the Kaplan-Meier estimator, log-rank test, and Cox regression. RESULTS: Our analyses identified two potential novel gene fusions, MBTTPS2,L0XNC01::SMS and AMACR::AMACR. These fusions were detected in all four studied cohorts, providing compelling evidence for the validity of these fusions and their relevance in PCa. We also found that the number of gene fusions detected in a patient sample was significantly associated with the time to biochemical recurrence in two of the four cohorts (log-rank test, p-value < 0.05 for both cohorts). This was also confirmed after adjusting the prognostic model for Gleason Grading Groups (Cox regression, p-values < 0.05). CONCLUSIONS: Our gene fusion characterization workflow revealed two potential novel fusions specific for PCa. We found evidence that the number of gene fusions was associated with the prognosis of PCa. However, as the quantitative correlations were only moderately strong, further validation and assessment of clinical value is required before potential application.

Gender-specific outcomes in immune checkpoint inhibitor therapy for advanced or metastatic urothelial cancer: a systematic review and meta-analysis.

PURPOSE: To analyze gender-specific differences in survival parameters in advanced or metastatic urothelial cancer patients undergoing immune checkpoint inhibition. METHODS: The primary aim of this systematic review and meta-analysis was to evaluate gender-specific differences in disease-free (DFS), progression-free (PFS), cancer-specific survival (CSS), event-free survival (EFS), overall survival (OS) and objective response rate (ORR). The sources MEDLINE, Embase and Cochrane Library were systematically searched from January 2010 to June 2022. No restrictions were made concerning language, study region or publication type. A comparison of gender-specific differences in survival parameters was performed using a random-effects meta-analysis. A risk of bias assessment was done using the ROBINS-I tool. RESULTS: Five studies were included. In a random-effect meta-analysis of the studies, PCD4989g and IMvigor 211 with both using atezolizumab, females were more likely to have better objective response rate (ORR) than men (OR 2.24; 95% CI 1.20-4.16; p = 0.0110). In addition, females had a comparable median OS to men (MD 1.16; 95% CI - 3.15-5.46; p = 0.598). In summary, comparing all results, a tendency was seen toward better response rates and survival parameters in female patients. The risk of bias assessment yielded an overall low risk of bias. CONCLUSIONS: There is a tendency toward better outcomes in women for immunotherapy in advanced or metastatic urothelial cancer, but only for the antibody atezolizumab women have a significantly better ORR. Unfortunately, many studies fail to report gender-specific outcomes. Therefore, further research is essential when aiming for individualized medicine. This research should address immunological confounders.

Prediction of Significant Prostate Cancer in Equivocal Magnetic Resonance Imaging Lesions: A High-volume International Multicenter Study.

BACKGROUND: Decision of performing prostate biopsy in men with Prostate Imaging Reporting and Data System (PI-RADS) 3 findings in prostate magnetic resonance imaging (MRI) is challenging as they have a low but still relevant risk of harboring significant prostate cancer (sPC). OBJECTIVE: To identify clinical predictors of sPC in men with PI-RADS 3 lesions in prostate MRI and to analyze the hypothetical effect of incorporating prostate-specific antigen density (PSAD) into biopsy decision. DESIGN, SETTING, AND PARTICIPANTS: We analyzed a retrospective multinational cohort from ten academic centers comprising 1476 men who underwent a combined prostate biopsy (MRI targeted plus systematic biopsy) between February 2012 and April 2021 due to a PI-RADS 3 lesion in prostate MRI. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the detection of sPC (ISUP ≥2) in a combined biopsy. Predictors were identified by a regression analysis. Descriptive statistics were applied to evaluate the hypothetical effect of involving PSAD into biopsy decision. RESULTS AND LIMITATIONS: Of all patients, 273/1476 (18.5%) were diagnosed with sPC. MRI-targeted biopsy diagnosed fewer sPC cases than combined strategy: 183/1476 (12.4%) versus 273/1476 (18.5%), p < 0.01. Age (odds ratio [OR] 1.10 [95% confidence interval {CI}: 1.05-1.15], p < 0.001), prior negative biopsy (OR 0.46 [0.24-0.89], p = 0.022), and PSAD (p < 0.001) were found to be independent predictors of sPC. Applying a PSAD cutoff of 0.15, 817/1398 (58.4%) biopsies would have been avoided at the cost of missing sPC in 91 (6.5%) men. Limitations were the retrospective design, heterogeneity of the study cohort due to the long inclusion period, and no central revision of MRI. CONCLUSIONS: Age, previous biopsy status, and PSAD were found to be independent predictors of sPC in men with equivocal prostate MRI. Implementation of PSAD into biopsy decision can avoid unnecessary biopsies. Clinical parameters such as PSAD need validation in a prospective setting. PATIENT SUMMARY: In this study, we looked for clinical predictors of significant prostate cancer in men with Prostate Imaging Reporting and Data System 3 lesions in prostate magnetic resonance imaging. We identified age, previous biopsy status, and especially prostate-specific antigen density as independent predictors.

Upper tract urothelial carcinoma in Germany: epidemiological data and surgical treatment trends in a total population analysis from 2006 to 2019.

PURPOSE: To report contemporary epidemiological data and treatment trends for upper tract urothelial carcinoma (UTUC) in Germany over a 14-year period. METHODS: We analyzed data from the nationwide German hospital billing database and the German cancer registry from 2006 to 2018/2019. The significance of changes over time was evaluated via regression analysis. Survival outcomes were calculated using the Kaplan-Meier method. RESULTS: There was a non-significant increase in the age-standardized incidence rate from 2.5/100,000 in 2006 to 2.9/100.000 in 2018. 13% of patients presented with lymph node metastasis and 7.6% of patients presented with distant metastasis at primary diagnosis. The 5-year overall survival was estimated at 45% and the 10-year overall survival at 32%. Endoscopic biopsies of the renal pelvis and ureter as well as ureteroscopies with excision/destruction of UTUC all increased significantly over the study period. The number of radical nephroureterectomies (RNU) for UTUC steadily increased from 1643 cases in 2006 to 2238 cases in 2019 (p < 0.005) with a shift from open surgery towards minimally invasive surgery. Complex reconstructive procedures like ileal ureter replacement or autotransplantation are rarely performed for urothelial carcinoma of the ureter. CONCLUSION: Diagnostic and therapeutic procedures for UTUC have increased and minimally invasive nephroureterectomy is the predominant approach concerning radical surgery in 2019.