Patient Benefits of Radical Prostatectomy in Certified Prostate Cancer Centers: Comparative Results from the Multicenter IMPROVE Study.

INTRODUCTION: We investigated differences in treatment outcomes following radical prostatectomy (RP) between certified centers (CCs) and noncertified centers (nCCs) within the IMPROVE study group. METHODS: A validated survey assessing various factors, including stress urinary incontinence (SUI) and decision regret (DR), was administered to 950 patients who underwent RP across 19 hospitals (12 CCs and 7 nCCs) at a median follow-up of 15 months after RP (interquartile range: 11-20). The response rate was 74%, with 703 patients participating, including 480 (68%) from CCs. Multivariate binary regression models were used to analyze differences between CCs and nCCs regarding the following binary endpoints: nerve-sparing (NS), positive surgical margins (PSM), SUI (defined as >1 safety pad), complications based on the Clavien-Dindo classification (grade ≥1, grade ≥3) and DR (>15 points indicating critical DR). RESULTS: Considering the multivariate analysis, the rate of NS surgery was lower in CCs than in nCCs (OR = 0.52; p = 0.004). No significant differences were observed in the PSM rate (OR = 1.67; p = 0.051), SUI (OR = 1.03; p = 0.919), and DR (OR = 1.00; p = 0.990). SUI (OR 0.39; p < 0.001) and DR (OR 0.62; p = 0.026) were reported significantly less frequently by patients treated with robotic-assisted RP, which was significantly more often performed in CCs than in nCCs (68.3% vs. 18%; p < 0.001). The total complication rate was 45% lower in CCs (OR = 0.55; p = 0.004), although the number of complications requiring intervention (Clavien-Dindo classification ≥3) did not differ significantly between CCs and nCCs (OR = 2.52; p = 0.051). CONCLUSION: Within the IMPROVE study group, similarly favorable outcomes after RP were found in both CCs and nCCs, which, however, cannot be transferred to the general treatment landscape of PCA in Germany. Of note, robotic-assisted RP was more often performed in CCs and associated with less SUI and DR, while open prostatectomy was the treatment of choice in low-volume nCCs. Future prospective and region wide studies should also investigate the surgeon caseload and experience as well as a spillover effect of the certification process on nCCs.

Patient's Desire and Real Availability Concerning Supportive Measures Accompanying Radical Prostatectomy: Differences between Certified Prostate Cancer Centers and Non-Certified Centers Based on Patient-Reported Outcomes within the Cross-Sectional Study Improve.

Certification as a prostate cancer center requires the offer of several supportive measures to patients undergoing radical prostatectomy (RP). However, it remains unclear how patients estimate the relevance of these measures and whether the availability of these measures differs between certified prostate cancer centers (CERTs) and non-certified centers (NCERTs). In 20 German urologic centers, a survey comprising questions on the relevance of 15 supportive measures was sent to 1000 patients at a median of 15 months after RP. Additionally, patients were asked to rate the availability of these measures using a four-item Likert scale. The aim of this study was to compare these ratings between CERTs and NCERTs. The response rate was 75.0%. In total, 480 patients underwent surgery in CERTs, and 270 in NCERTs. Patients rated 6/15 supportive measures as very relevant: preoperative medical counselling concerning treatment options, a preoperative briefing answering last questions, preoperative pelvic floor exercises (PFEs), postoperative PFEs, postoperative social support, and postoperative rehabilitation addressing physical fitness recovery. These ratings showed no significant difference between CERTs and NCERTs (p = 0.133-0.676). In addition, 4/9 of the remaining criteria were rated as more detailed by patients in CERTs. IMPROVE represents the first study worldwide to evaluate a patient-reported assessment of the supportive measures accompanying RP. Pertinent offers vary marginally between CERTs and NCERTs.

Patients Regret Their Choice of Therapy Significantly Less Frequently after Robot-Assisted Radical Prostatectomy as Opposed to Open Radical Prostatectomy: Patient-Reported Results of the Multicenter Cross-Sectional IMPROVE Study.

Patient's regret (PatR) concerning the choice of therapy represents a crucial endpoint for treatment evaluation after radical prostatectomy (RP) for prostate cancer (PCA). This study aims to compare PatR following robot-assisted (RARP) and open surgical approach (ORP). A survey comprising perioperative-functional criteria was sent to 1000 patients in 20 German centers at a median of 15 months after RP. Surgery-related items were collected from participating centers. To calculate PatR differences between approaches, a multivariate regressive base model (MVBM) was established incorporating surgical approach and demographic, center-specific, and tumor-specific criteria not primarily affected by surgical approach. An extended model (MVEM) was further adjusted by variables potentially affected by surgical approach. PatR was based on five validated questions ranging 0−100 (cutoff >15 defined as critical PatR). The response rate was 75.0%. After exclusion of patients with laparoscopic RP or stage M1b/c, the study cohort comprised 277/365 ORP/RARP patients. ORP/RARP patients had a median PatR of 15/10 (p < 0.001) and 46.2%/28.1% had a PatR >15, respectively (p < 0.001). Based on the MVBM, RARP patients showed PatR >15 relative 46.8% less frequently (p < 0.001). Consensual decision making regarding surgical approach independently reduced PatR. With the MVEM, the independent impact of both surgical approach and of consensual decision making was confirmed. This study involving centers of different care levels showed significantly lower PatR following RARP.

The Diagnostic Value of the Added MR Imaging of the Scrotum in the Preoperative Workup of Sonographically Indeterminate Testicular Lesions-A Retrospective Multicenter Analysis.

BACKGROUND: The purpose of this study was to retrospectively analyze the diagnostic accuracy of magnetic resonance imaging (MRI) examinations of the scrotum in comparison with standard ultrasound (US) and histopathology. METHODS: A retrospective multi-center analysis of MRI examinations of the scrotum performed between 06/2008 and 04/2021 was conducted. RESULTS: A total of n = 113 patients were included. A total of 53 histopathologies were available, with 52.8% malignant and 50.9% benign findings. Related to histopathology, imaging was true negative, false negative, false positive, and true positive in 4.1%, 2.1%, 25.0% and 37.5% for standard ultrasound (US) and 9.1%, 1.8%, 25.5% and 43.6% for MRI. Sensitivity, specificity, positive predictive value and negative predictive value were 94.7%, 20.0%, 36.0% and 88.9% for US and 85.7%, 72.8%, 52.1% and 93.7% for MRI, respectively. Benign lesions were significantly smaller than malignant ones in standard US (p = 0.001), histopathology (p = 0.001) and MRI (p = 0.004). The size of malignant tumors did not differ significantly between histopathology and standard US (0.72) and between histopathology and MRI (p = 0.88). CONCLUSIONS: MRI shows good sensitivity and specificity for the estimation of testicular tumors in this collective. Benign lesions are significantly smaller than malignant ones. Both MRI and US can estimate the size of malignant tumors adequately.

Salvage Radiotherapy for Recurrent Prostate Cancer after High-Intensity Focused Ultrasound Therapy: Quality of Life and Functional Outcome.

INTRODUCTION: The aim of this study was to evaluate toxicity, oncological and functional outcome, and quality of life after salvage radiotherapy for recurrent prostate cancer after high-intensity focused ultrasound (HIFU) therapy. METHODS: A total of 13 patients undergoing salvage radiotherapy for biopsy-proven prostate cancer recurrence after HIFU therapy were included and followed up every 3 months. Oncological outcome (by PSA measurements), toxicity (according to CTCAE criteria), and functional outcome were evaluated. Quality of life was assessed by standardized questionnaires (QLQ-C30 and QLQ-PR25) at baseline, 3 months, and 12 months after salvage treatment. RESULTS: Median age of patients was 80 years (interquartile range [IQR] 75-82). Patients underwent normofractionated salvage radiotherapy with median 73.6 Gy. PSA nadir was reached at 6 months and was 0.2 ng/mL. Median follow-up was 76 months (IQR 55-96). Biochemical recurrence occurred in 3 patients (23.1%) at a median of 36.4 months. No gastrointestinal (GI) or genitourinary (GU) toxicity ≥ grade 3 was noted during follow-up. Early and late grade II GI toxicity occurred in 1 patient (7.7%), respectively. GU toxicity grade II was noted in up to 53.8% at 3 months and 61.5% at 12 months. In terms of health-related quality of life, there was no statistically significant difference at 3 and 12 months compared to the baseline. Only differences were seen in sexual functioning (3 and 12 months) and in diarrhea (3 months), affecting patients' wellbeing. DISCUSSION/CONCLUSION: Salvage radiotherapy after HIFU treatment can be performed safely, thereby providing acceptable recurrence-free survival without severe impact on post-interventional quality of life.

[Knowledge of German-speaking urologists regarding the association between penile cancer and human papilloma virus: results of a survey of the European PROspective Penile Cancer Study (E-PROPS)]. / Kenntnisse von deutschsprachigen Urologen zur Häufigkeit der Assoziation des Peniskarzinoms mit dem Humanen Papillomavirus ­ Survey-Ergebnisse der European PROspective Penile Cancer Study (E-PROPS).

BACKGROUND: A recent meta-analysis showed that penile cancer (PeC) is associated with the human papilloma virus (HPV) in 50 % of patients in Europe. It is unknown whether urologists are aware of the impact of viral carcinogenesis. METHODS: A (German-language) survey comprising 14 items was created and sent to urologists of 45 clinical centres in Germany (n = 34), Austria (n = 8), Switzerland (n = 2) and Italy/South Tyrol (n = 1) once in Q3/2018. According to a predefined quality standard, a total of 557 surveys were eligible for final data analysis (response rate: 85.7 %). Among other questions, urologists were asked to state the frequency of HPV-associated PeC in Europe. 4 potential answers were provided: (A)-"< 25 %", (B)-"25 - 50 %", (C)-"> 50 - 75 %", (D)-"level of association unknown". For the final calculation, a tolerance of ±â€Š50 % was considered acceptable, so B and C were deemed correct answers. Based on a bootstrap-adjusted multivariate logistic regression model, criteria independently predicting a correct answer were identified. RESULTS: Categories A-D were selected in 19.2 % (n = 107), 48.8 % (n = 272), 12.9 % (n = 72) and 19 % (n = 106), respectively, representing a rate of 61.8 % of urologists (n = 344) reaching the endpoint (B + C). Autonomous performance of chemotherapy for PeC by urologists within the given centre (OR 1.55, p[Bootstrap] = 0.036) and the centre's number of urological beds (OR 1.02, p[Bootstrap] = 0.025) were the only parameters showing a significant independent impact on the endpoint. In contrast, the status of a university centre (p = 0.143), a leading position of the responding urologist (p = 0.375) and the number of PeC patients treated per year and centre (p = 0.571) did not significantly predict a correct answer. CONCLUSIONS: Our results demonstrate insufficient knowledge on the association of PeC and HPV among German-speaking urologists.

External validation of two MRI-based risk calculators in prostate cancer diagnosis.

BACKGROUND: The diagnosis of (significant) prostate cancer ((s)PC) is impeded by overdiagnosis and unnecessary biopsy. Risk calculators (RC) have been developed to mitigate these issues. Contemporary RCs integrate clinical characteristics with mpMRI findings. OBJECTIVE: To validate two of these models-the MRI-ERSPC-RC-3/4 and the risk model of van Leeuwen. METHODS: 265 men with clinical suspicion of PC were enrolled. Every patient received a prebiopsy mpMRI, which was reported according to PI-RADS v2.1, followed by MRI/TRUS fusion-biopsy. Cancers with ISUP grade ≥ 2 were classified as sPC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statistical analysis was performed by comparing discrimination, calibration, and clinical utility RESULTS: There was no significant difference in discrimination between the RCs. The MRI-ERSPC-RC-3/4-RC showed a nearly ideal calibration-slope (0.94; 95% CI 0.68-1.20) than the van Leeuwen model (0.70; 95% CI 0.52-0.88). Within a threshold range up to 9% for a sPC, the MRI-ERSPC-RC-3/4-RC shows a greater net benefit than the van Leeuwen model. From 10 to 15%, the van Leeuwen model showed a higher net benefit compared to the MRI-ERSP-3/4-RC. For a risk threshold of 15%, the van Leeuwen model would avoid 24% vs. 14% compared to the MRI-ERSPC-RC-3/4 model; 6% vs. 5% sPC would be overlooked, respectively. CONCLUSION: Both risk models supply accurate results and reduce the number of biopsies and basically no sPC were overlooked. The van Leeuwen model suggests a better balance between unnecessary biopsies and overlooked sPC at thresholds range of 10-15%. The MRI-ERSPC-RC-3/4 risk model provides better overall calibration.

Adherence to European Association of Urology and National Comprehensive Cancer Network Guidelines Criteria for Inguinal and Pelvic Lymph Node Dissection in Penile Cancer Patients-A Survey Assessment in German-speaking Countries on Behalf of the European Prospective Penile Cancer Study Group.

BACKGROUND: Urologists' adherence to European Association of Urology and National Comprehensive Cancer Network guideline recommendations to perform inguinal (ILND) and pelvic (PLND) lymph node dissection in penile cancer (PC) patients is not known. OBJECTIVE: To assess a German-speaking European cohort of urologists based on their criteria to perform ILND and PLND in PC patients. DESIGN, SETTING, AND PARTICIPANTS: A 14-item survey addressing general issues of PC treatment was developed and sent to 45 clinical centers in Germany (n = 34), Austria (n = 8), Switzerland (n = 2), and Italy (n = 1). INTERVENTION: Two of the 14 questions assessed the criteria to perform ILND and ipsilateral PLND. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Correct responses for ILND and PLND criteria were assessed. Based on a multivariate logistic-regression-model, criteria independently predicting guideline adherence were identified. RESULTS AND LIMITATIONS: In total, 557 urologists participated in the survey, of whom 43.5%, 19.3%, and 37.2% were residents in training, certified, and in leading positions, respectively. ILND and PLND criteria were correctly identified by 35.2% and 23.9%, respectively. Of the participants, 23.3% used external sources for survey completion. The use of auxiliary tools (odds ratio [OR] 1.57; p[bootstrapped] = 0.028) and participants outside of Germany (OR 0.56; p[bootstrapped] = 0.006) were predictors of ILND guideline adherence. The number of PC patients treated yearly (p = 0.012; OR 1.06) and the use of auxiliary tools (p < 0.001; OR 5.88) were predictors of PLND adherence. Department size, healthcare status, professional status, and responsibility for PC surgery did not predict endpoints. Limitations include sample size and results in comparison with retrospective studies. CONCLUSIONS: Our results demonstrate overall suboptimal knowledge of the correct indications to perform ILND and PLND in PC patients among the surveyed urologists. We propose that governments and healthcare providers should be encouraged to centralize PC management. PATIENT SUMMARY: The management of inguinal and pelvic lymph nodes is crucial for the survival of penile cancer patients. Disease rarity mandates referral to clinical practice guidelines for appropriate treatment selection.

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-however, 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.

External validation of novel magnetic resonance imaging-based models for prostate cancer prediction.

OBJECTIVES: To validate, in an external cohort, three novel risk models, including the recently updated European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculator, that combine multiparametric magnetic resonance imaging (mpMRI) and clinical variables to predict clinically significant prostate cancer (PCa). PATIENTS AND METHODS: We retrospectively analysed 307 men who underwent mpMRI prior to transperineal ultrasound fusion biopsy between October 2015 and July 2018 at two German centres. mpMRI was rated by Prostate Imaging Reporting and Data System (PI-RADS) v2.0 and clinically significant PCa was defined as International Society of Urological Pathology Gleason grade group ≥2. The prediction performance of the three models (MRI-ERSPC-3/4, and two risk models published by Radtke et al. and Distler et al., ModRad and ModDis) were compared using receiver-operating characteristic (ROC) curve analyses, with area under the ROC curve (AUC), calibration curve analyses and decision curves used to assess net benefit. RESULTS: The AUCs of the three novel models (MRI-ERSPC-3/4, ModRad and ModDis) were 0.82, 0.85 and 0.83, respectively. Calibration curve analyses showed the best intercept for MRI-ERSPC-3 and -4 of 0.35 and 0.76. Net benefit analyses indicated clear benefit of the MRI-ERSPC-3/4 risk models compared with the other two validated models. The MRI-ERSPC-3/4 risk models demonstrated a discrimination benefit for a risk threshold of up to 15% for clinically significant PCa as compared to the other risk models. CONCLUSION: In our external validation of three novel prostate cancer risk models, which incorporate mpMRI findings, a head-to-head comparison indicated that the MRI-ERSPC-3/4 risk model in particular could help to reduce unnecessary biopsies.

Clinical characteristics, treatment outcomes and potential novel therapeutic options for patients with neuroendocrine carcinoma of the prostate.

BACKGROUND: Neuroendocrine carcinomas of the prostate (NEPCs) are rare tumors with poor prognosis. While platinum and etoposide-based chemotherapy regimens (PE) are commonly applied in first-line for advanced disease, evidence for second-line therapy and beyond is very limited. METHODS: Retrospective analysis of all patients with NEPCs including mixed differentiation with adenocarcinoma component and well differentiated neuroendocrine tumors (NETs, carcinoids) at two high-volume oncological centers between 12/2000 and 11/2017. RESULTS: Of 46 identified patients 39.1 % had a prior diagnosis of prostatic adenocarcinoma only, 43.5 % had a mixed differentiation at NEPC diagnosis, 67.4 % developed visceral metastases, 10.9 % showed paraneoplastic syndromes. Overall survival (OS) from NEPC diagnosis was 15.5 months, and significantly shorter in patients with a prior prostatic adenocarcinoma (5.4 vs. 32.7 months, p=0.005). 34 patients received palliative first-line systemic therapy with a median progression-free survival (PFS) of 6.6 months, mostly PE. Overall response rate (ORR) for PE was 48.1 %. 19 patients received second-line therapy, mostly with poor responses. Active regimens were topotecan (1 PR, 3 PD), enzalutamide (1 SD), abiraterone (1 SD), FOLFIRI (1 SD), and ipilimumab+nivolumab (1 PR). One patient with prostatic carcinoid was sequentially treated with octreotide, peptide receptor radionuclide therapy and everolimus, and survived for over 9 years. CONCLUSIONS: EP in first-line shows notable ORR, however limited PFS. For second-line therapy, topotecan, FOLFIRI, enzalutamide, abiraterone and immune checkpoint blockade are treatment options. Prostatic carcinoids can be treated in analogy to well differentiated gastrointestinal NETs.

Survival outcomes of patients with germ cell tumors treated with high-dose chemotherapy for refractory or relapsing disease.

INTRODUCTION: Male patients with metastatic germ cell tumors can be cured in up to 96% of cases depending on stage and IGCCCG prognosis group. Treatment in relapse consists of conventional or high-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) combined with local treatment modalities. RESULTS: Most patients were classified as poor risk according to IGCCCG (n = 24; 52%) and as intermediate (n = 12), high (n = 16), or very high risk (n = 9) at time of first relapse according to IPFSG criteria. In 67% of patients (n = 31) HDCT/ASCT was performed as first salvage treatment in relapse or for primary refractory disease following first line chemotherapy. In 46% of patients (n = 21) progressive disease was documented after mobilization and prior to HDCT/ASCT. Median progression free survival (mPFS) was 7.4 months (95% confidence interval (CI): 1.3-13.6) while median overall survival (mOS) was 22.2 months (95% CI: 8.9-35.5). When stratified for IPFSG risk group, mPFS (p < 0.001) and mOS (p = 0.009) differed significantly between risk groups (very low vs. low vs. intermediate vs. high vs. very high). Metastases to liver/bone/brain and platinum refractory disease were independent risk factors for inferior PFS (p = 0.024; p = 0.008) but not OS. MATERIALS AND METHODS: Forty-six patients treated with HDCT/ASCT at the university clinics in Heidelberg and Nuremberg between 2000-2016 were identified and analyzed. Data was collected retrospectively. CONCLUSIONS: HDCT/ASCT offers a potential curative strategy for patients with relapsed GCT. Improvement is still needed in patients with intermediate, high, and very high IPFSG risk group.

The Value of PSA Density in Combination with PI-RADS™ for the Accuracy of Prostate Cancer Prediction.

PURPOSE: Multiparametric magnetic resonance imaging has an emerging role in prostate cancer diagnostics. In addition, clinical information is a reliable predictor of significant prostate cancer. We analyzed whether the negative predictive value of multiparametric magnetic resonance imaging to rule out significant prostate cancer could be improved using clinical factors, especially prostate specific antigen density. MATERIALS AND METHODS: A total of 1,040 consecutive men with suspicion of prostate cancer underwent multiparametric magnetic resonance imaging first, followed by transperineal systematic and magnetic resonance imaging-transrectal ultrasound fusion guided biopsy. Logistic regression analyses were performed to test different clinical factors as predictors of significant prostate cancer and build nomograms. To simplify these nomograms for clinical use patients were stratified into 3 prostate specific antigen density groups, including group 1-less than 0.07, group 2-0.07 to 0.15 and group 3-greater than 0.15 ng/ml/ml. After stratification we calculated the negative predictive value of a PI-RADS (Prostate Imaging Reporting and Data System) Likert score of less than 3. Significant prostate cancer was defined as a Gleason score of 3 + 4 or greater. High grade prostate cancer was defined as a Gleason score of 4 + 3 or greater. RESULTS: Overall 451 men were diagnosed with significant prostate cancer, including 187 with a Gleason score of 4 + 3 or greater. On ROC curve analyses the predictive power of the developed nomogram for significant prostate cancer showed a higher AUC than that of PI-RADS alone (0.79 vs 0.75, p <0.001). The negative predictive value of harboring significant prostate cancer increased in men with unsuspicious magnetic resonance imaging from 79% up to 89% when prostate specific antigen density was 0.15 ng/ml/ml or less. In the repeat biopsy setting the negative predictive value of significant prostate cancer increased from 83% to 93%. The negative predictive value to harbor high grade prostate cancer increased from 92% up to 98% in the entire cohort. CONCLUSIONS: Using prostate specific antigen density combined with multiparametric magnetic resonance imaging improved the negative predictive value of PI-RADS scoring. By increasing the probability of ruling out significant prostate cancer approximately 20% of unnecessary biopsies could be avoided safely.