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.

Urologist communication is a primary factor leading to erectile dysfunction treatment postprostatectomy.

BACKGROUND: Studies have shown insufficient utilization of care for patients with erectile dysfunction (ED) after radical prostatectomy (RP). AIM: The aim of this study was to evaluate variables associated with barriers to seeking and receiving ED treatment. METHODS: In this multicenter prospective cross-sectional study, the functional outcomes of 936 patients were assessed 10 to 15 years after RP. A total of 525 patients with ED or incontinence were asked about their treatment experiences or lack thereof. The data were analyzed using the chi-square test, t test, and multivariate logistic analyses. OUTCOMES: Patients answered validated questionnaires regarding information sources, communication with their partner and urologist, and barriers to ED treatment. RESULTS: Of the 525 patients, 80 were not available to survey. A total of 304 patients answered the survey (response: 68.0%). A total of 246 patients had ED and were included in this study. The mean age at surgery was 64.4 ± 6.1 years, and the mean age at the time of this survey was 77.1 ± 6.2 years. The mean follow-up duration was 12.7 ± 1.5 years. Forty-six percent (n = 114 of 246) of the patients had never received ED treatment. The most important conversation partners regarding the ED were the partner (69% [n = 169 of 246]) and the urologist (48% [n = 118 of 246]). Patients who never received ED treatment were less likely to have conversations with their urologist (34% vs 60%; P < .001), had less support (51% vs 68%; P = .01), and had less interest in sex from their partner (20% vs 40%; P = .001). Communication with other groups (general practitioners, other physicians, family, friends, and the Internet) had no influence on ED treatment utilization. The most relevant barrier to receiving ED treatment was the belief that treatment would not help (65%). No interest in sex from their partner (odds ratio, 3.9) and no conversation with their urologist about ED (odds ratio, 2.9) were found to be independent predictors of not receiving ED treatment. CLINICAL IMPLICATIONS: Urologists should have enhanced awareness of how to approach patients directly about their ED and actively offer them treatment options. STRENGTHS AND LIMITATIONS: These results should be further validated in a multicenter, prospective study. Response bias may have affected the results. Furthermore, the current cohort was relatively old. CONCLUSION: This study revealed that no interest in sex from one's partner and insufficient communication with a urologist were relevant barriers to insufficient utilization of ED treatment after RP.

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.

Treatment trends for undescended testis and impact of guideline changes a medical health care analysis of orchidopexy and cryptorchidism in Germany between 2006 und 2020.

BACKGROUND: The last decades revealed new scientific knowledge regarding the fertility and potential malignancy of undescended testis AQ2(UDT). Accordingly, many guidelines changed their recommendation concerning timing of therapy, with the goal of an earlier time of surgery. METHODS: We analyzed the number of new diagnosis and performed surgeries in predefined age groups provided by the obligatory annual reports of German hospitals in the reimbursement.INFO"-tool between 2006 and 2020. RESULTS: Overall, 124,741 cases were analyzed. We showed a slight increase in performed surgeries in the first year by 2% per year with a main increase till 2011, a constant number of surgeries between first and 4th year and a decrease of surgeries between 5 and 14th year of living with a main decrease till 2009 by 3% per year. CONCLUSION: Even if our results illustrate an increasing adaption of the guideline's recommendation, there is still a significant number of patients who receive later treatment. More research about the reasons and circumstances for the latter is needed.

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.

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.

Declining utilization of urodynamic studies in urological care in Germany: time to say goodbye?

INTRODUCTION: The number of urodynamic studies (UDS) has been declining steadily in recent decades, yet the reasons behind this trend remain poorly understood. This study aims to investigate the structural aspects of UDS in urology and explore the factors contributing to this decline. MATERIAL & METHODS: We surveyed all urological departments performing UDS as well as a representative sample of private practices in Germany in 2023. We examined structural situation, waiting times, capacities and limitations of UDS. All invasive urodynamic examinations were defined as UDS. RESULTS: In 2019, 259/474 (55%) urological departments in Germany performed UDS. 206/259 (80%) urological departments responded to the survey. 163/200 (82%) urological departments stated that their capacities were exhausted, a main reason being lack of medical and nursing staff. 54.8% urological departments performed more than 50% of their UDS for referring physicians. Urological departments with a low number of UDS/year (≤ 100) showed a shorter waiting time (up to 4 weeks: 49% vs. 30%; p = 0.01), reduced UDS capacities (55% vs. 12%; p < 0.001) and these capacities were often not fully utilized (25% vs. 9%; p = 0.007). 122/280 (44%) office urologists responded to the survey. 18/122 (15%) office urologists performed UDS. Main reasons for not offering UDS were lack of personnel and low reimbursement. CONCLUSION: In German urological departments, UDS capacities are consistently fully utilized, primarily due to staffing shortages. This trend towards centralization prompts questions about the role of UDS in urologists' training.

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.

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.

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.

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.

The Androgen Hormone-Induced Increase in Androgen Receptor Protein Expression Is Caused by the Autoinduction of the Androgen Receptor Translational Activity.

The androgen receptor (AR) plays a central role in prostate, muscle, bone and adipose tissue. Moreover, dysregulated AR activity is a driving force in prostate cancer (PCa) initiation and progression. Consequently, antagonizing AR signalling cascades via antiandrogenic therapy is a crucial treatment option in PCa management. Besides, very high androgen levels also inhibit PCa cells' growth, so this effect could also be applied in PCa therapy. However, on the molecular and cellular level, these mechanisms have hardly been investigated so far. Therefore, the present study describes the effects of varying androgen concentrations on the viability of PCa cells as well as localization, transactivation, and protein stability of the AR. For this purpose, cell viability was determined via WST1 assay. Alterations in AR transactivity were detected by qPCR analysis of AR target genes. A fluorescent AR fusion protein was used to analyse AR localization microscopically. Changes in AR protein expression were detected by Western blot. Our results showed that high androgen concentrations reduce the cell viability in LNCaP and C4-2 cell lines. In addition, androgens have been reported to increase AR transactivity, AR localization, and AR protein expression levels. However, high androgen levels did not reduce these parameters. Furthermore, this study revealed an androgen-induced increase in AR protein synthesis. In conclusion, inhibitory effects on cell viability by high androgen levels are due to AR downstream signalling or non-genomic AR activity. Moreover, hormonal activation of the AR leads to a self-induced stabilization of the receptor, resulting in increased AR activity. Therefore, in clinical use, a therapeutic reduction in androgen levels represents a clinical target and would lead to a decrease in AR activity and, thus, AR-driven PCa progression.

Acceptance and efficacy of recommended adjuvant radiotherapy in patients with positive lymph nodes at radical prostatectomy: a preference-based study.

PURPOSE: To investigate acceptance and efficacy of recommended adjuvant radiotherapy in patients with positive lymph nodes at radical prostatectomy. METHODS: Among 495 patients with positive lymph nodes who consecutively underwent radical prostatectomy between 2007 and 2017, we investigated 347 patients who were recommended to undergo adjuvant radiotherapy by a multidisciplinary post-therapeutic tumor board and in whom information whether such treatment was eventually given was available. The median follow-up for censored patients was 5.4 years. Univariate analyses were performed using Kaplan-Meier curves, Mantel-Haenszel hazard ratios and log rank tests. Proportional hazard models for competing risks were used for multivariable analyses. RESULTS: Adjuvant radiotherapy was independently associated with lower overall mortality and in high-risk patients (Gleason score 8-10 or three or more involved lymph nodes) also with lower prostate cancer-specific mortality. In patients with a Gleason score of 8-10 or three or more involved lymph nodes, the hazard ratio for adjuvant radiotherapy was 0.455 (95% confidence interval 0.257-0.806, p = 0.0069) for overall and 0.426 (95% confidence interval 0.201-0.902, p = 0.0259) for prostate cancer-specific mortality. Among patients receiving adjuvant radiotherapy, there was a trend to lower mortality when such treatment was combined with adjuvant androgen deprivation. CONCLUSION: Adjuvant radiotherapy decreased mortality in patients with positive lymph nodes at radical prostatectomy with further disease factors but not in patients with low-risk disease. Simultaneous androgen deprivation might increase efficacy. Multidisciplinary recommendations may possibly increase the use of adjuvant radiotherapy in this setting.

Negative multiparametric magnetic resonance imaging for prostate cancer: further outcome and consequences.

PURPOSE: EAU guidelines recommend multiparametric MRI of the prostate (mpMRI) prior to biopsy to increase accuracy and reduce biopsies. Whether biopsy can be avoided in case of negative mpMRI remains unclear. Aim of this study is to evaluate predictors of overall prostate cancer (PCa) in negative mpMRI. METHODS: A total of 216 patients from 2018 to 2020 with suspicion of PCa and negative mpMRI (PI-RADS ≤ 2) were interviewed by telephone about outcome and further follow-up. Clinically significant PCa (csPCa) was defined as ISUP ≥ 2. Patients with vs. without biopsy and with vs. without PCa were compared. Univariate and multivariate analyses were performed to evaluate predictors of PCa occurrence in patients with negative mpMRI. RESULTS: 15.7% and 5.1% of patients with PI-RADS ≤ 2 on mpMRI showed PCa and csPCa, respectively. PCa patients had higher PSAD (0.14 vs. 0.09 ng/ml2; p = 0.001) and lower prostate volume (50.5 vs. 74.0 ml; p = 0.003). Patients without biopsy (25%) after MRI were older (69 vs. 65.5 years; p = 0.027), showed lower PSA (5.7 vs. 6.73 ng/ml; p = 0.033) and lower PSA density (0.09 vs. 0.1 ng/ml2; p = 0.027). Multivariate analysis revealed age (OR 1.09 [1.02-1.16]; p = 0.011), prostate volume (OR 0.982 [0.065; 0.997]; p = 0.027), total PSA level (OR 1.22 [1.01-1.47], p = 0.033), free PSA (OR 0.431 [0.177; 0.927]; p = 0.049) and no PI-RADS lesion vs PI-RADS 1-2 lesion (OR 0.38 [0.15-0.91], p = 0.032.) as predictive factors for the endpoint presence of PCa. CONCLUSIONS: Biopsy for selected patient groups (higher age, prostate volume and free PSA as well as lower PSA-Density) with negative mpMRI can be avoided, if sufficient follow-up care is guaranteed. Detailed counseling regarding residual risk for undetected prostate cancer should be mandatory.

Alternative- and focal therapy trends for prostate cancer: a total population analysis of in-patient treatments in Germany from 2006 to 2019.

PURPOSE: Focal therapy (FT) offers an alternative approach for prostate cancer (PCa) treatment in selected patients. However, little is known on its actual establishment in health care reality. PATIENTS AND METHODS: We defined FT as high-intensity focused ultrasound (HIFU), hyperthermia ablation, cryotherapy, transurethral ultrasound ablation (TULSA) or vascular-targeted photodynamic therapy (VTP) TOOKAD®. We analyzed the nationwide German hospital billing database for a PCa diagnosis in combination with FT. For analyses on the hospital level, we used the reimbursement.INFO tool based on hospitals' quality reports. The study period was 2006 to 2019. RESULTS: We identified 23,677 cases of FT from 2006 to 2019. Considering all PCa cases with surgery, radiotherapy or FT, the share of FT was stable at 4%. The annual caseload of FT increased to a maximum of 2653 cases in 2008 (p < 0.001) and then decreased to 1182 cases in 2014 (p < 0.001). Since 2015, the cases of FT remained on a plateau around 1400 cases per year. The share of HIFU was stable at 92-96% from 2006 to 2017 and decreased thereafter to 75% in 2019 (p = 0.015). In 2019, VTP-TOOKAD® increased to 11.5% and TULSA to 6%. In 2006, 21% (62/299) of urological departments performed FT and 20 departments reached > 20 FT procedures. In 2019, 16% (58/368) of urological departments performed FT and 7 departments reached > 20 FT. In 2019, 25 urological departments offered FT other than HIFU: 5 centers hyperthermia ablation, 11 centers VTP TOOKAD®, 3 centers cryotherapy, 6 centers TULSA. CONCLUSION: The FT development in Germany followed the Gartner hype cycle. While HIFU treatment is the most commonly performed FT, the share of newer FT modalities such as VTP-TOOKAD® and TULSA is remarkably increasing.

The Role of PSMA PET Imaging in Prostate Cancer Theranostics: A Nationwide Survey.

INTRODUCTION: Prostate-specific membrane antigen (PSMA)-based imaging and theranostics have played an important role in the diagnosis, staging, and treatment of prostate cancer (PCa). We aimed to evaluate the acceptance and use of PSMA theranostics among German urologists. METHODS: An anonymous online questionnaire was sent via survio.com to the members of the German Society of Urology (DGU). RESULTS: Seventy-two percent of participants performed PSMA positron emission tomography (PET) imaging regularly in biochemically recurrent PCa. Overall, 61% of participants considered PSMA-radioligand therapy to be very useful or extremely useful. PSMA PET imaging in high-risk PCa is more often considered by urologists working in a university setting than in nonuniversity settings or medical practices (51% vs. 25%, p < 0.001). Most perform PSMA-radioligand therapy as an option after all approved systemic treatments for metastatic castration-resistant PCa (56%) or after cabazitaxel (14%). A total of 93.9% and 70.3% of respondents consider the lack of reimbursement by health insurance to be the main obstacle to using PSMA PET imaging or radioligand therapy, respectively. DISCUSSION/CONCLUSION: PSMA-based imaging/theranostics are already widely applied but would find even more widespread use if reimbursement is clearly regulated by health insurance in Germany.

Decision Regret and Quality of Life after Focal Therapy with Vascular-Targeted Photodynamic Therapy (TOOKAD®) for Localized Prostate Cancer.

PURPOSE: The aim of the study was to assess quality of life (QoL), decision involvement, and decisional regret after treatment with vascular-targeted photodynamic therapy (VTP) (TOOKAD®) for unilateral low-risk prostate cancer. METHODS: Validated questionnaires (EORTC QLQ-C30 and QLQ-PR25) capturing QoL post-treatment, involvement in decision-making (Control Preferences Scale) and decision regret (Decisional Regret Scale), were given to patients at the 12-month visit after undergoing VTP at our institution between May 2018 and February 2021. RESULTS: Out of 44 patients, 36 patients were included in this study and 31 (86.1%) responded to the questionnaires. Mean overall health score capturing QoL at 12 months was 79.3 (standard deviation: ±18.1). 70.9% of the patients (n = 22) had no decision regret, and 67.8% of men (n = 21) had an active role in decision-making. In control biopsy at 12 months post-treatment, 19.4% of patients (n = 7) presented with local recurrence and progression to higher Gleason score (GS) was found in 13.8% of patients (n = 5). Patients (n = 3) presenting with tumor recurrence or progression to higher GS in control biopsy showed a significantly higher level of decision regret (p < 0.009). CONCLUSION: Only 9.7% of men (n = 3) felt a strong emotion of regret at 12 months after VTP. Level of decision regret was significantly higher in patients with local recurrence or tumor progression detected in control biopsy. QoL was stable after VTP.

Decreasing Number of Urodynamics in Urological and Gynaecological Clinics Reflects Decreased Importance for Surgical Indications: German Population-Based Data from 2013 to 2019.

INTRODUCTION: The routine use of urodynamic studies (UDS) has been questioned. Additionally, the material and personnel costs are poorly remunerated. We aimed to analyse the UDS utilization in Germany. METHODS: We analysed UDS performed by hospitals based on quality reports from 2013 to 2019. A representative sample of 4 million insured persons was used to estimate outpatient UDS utilization from 2013 to 2018. RESULTS: There was an overall decrease of 14% in UDS in Germany from 2013 to 2018 (60,980 to 52,319; p = 0.003). In the outpatient sector, there was a slight non-continuous drop of 11% from 34,551 to 30,652 from 2013 to 2018 (p = 0.06). UDS utilization in hospitals decreased by 26% from 26,429 in 2013 to 19,453 in 2019 (p = 0.004). University hospitals showed a smaller decrease (3,007 to 2,685; p = 0.02). In urology, the number of UDS (11,758 to 6,409; p < 0.001) and the number of performing departments (328 to 263 clinics; p < 0.001) decreased. Gynaecological departments also showed a decrease in UDS (1,861 to 866; p < 0.001) and performing departments (159 to 68; p < 0.001). However, in paediatrics, there was an increase in UDS (1,564 to 2,192; p = 0.02). By age, the number of children remained constant (1,371 to 1,252; p = 0.2), but there was a strong decrease seen in 60- to 79-year-olds (9,792 to 5,564; p < 0.001). CONCLUSION: UDS appear to be less important in the indication for surgery. Despite high resource expenditure and low remuneration, the decrease in urodynamics in the outpatient sector is less pronounced, indicating a trend to perform UDS in an outpatient setting.