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Purpose: A substantial proportion of men with localized prostate cancer (lPCa) later regret their treatment decision. We aimed to identify factors contributing to decisional regret. Methods: We conducted a longitudinal study, in which men with lPCa were surveyed at four measurement points: T0 (baseline) = prior to treatment; T1 = 6; T2 = 12; T3 = 18 months after baseline. χ2-tests and independent t-tests were used to compare men undergoing different treatments [Active Surveillance (AS) vs. local treatment]. Logistic regression models were fitted to investigate the associations between predictors (time pressure, information provided by the urologist, impairment of erectile functioning, satisfaction with sexual life) and the criterion decisional regret. Results: At baseline, the sample included N = 176 men (AS: n = 100; local treatment: n = 76). At T2 and T3, men after local therapies reported higher regret than men under AS. Decisional regret at T3 was predicted by time pressure at baseline (OR 2.28; CI 1.04–4.99; p < 0.05), erectile dysfunction at T2 and T3 (OR 3.40; CI 1.56–7.42; p < 0.01), and satisfaction with sexual life at T1–T3 (OR 0.44; CI 0.20–0.96; p < 0.05). Conclusions: Time pressure, erectile dysfunction, and satisfaction with sexual life predict decisional regret in men with lPCa. Mitigating time pressure and realistic expectations concerning treatment side effects may help to prevent decisional regret in PCa survivors. Trial registration number: DRKS00009510; date of registration: 2015/10/28. [ABSTRACT FROM AUTHOR]

Introduction: Sunitinib and pazopanib are both standard first-line therapies for clear-cell metastatic renal-cell carcinoma (mRCC). Everolimus is a well-established second-line treatment. Objective: To estimate the efficacy and safety of second-line everolimus following pazopanib or sunitinib. Methods: SUNPAZ was an open-label, phase 4 clinical trial of everolimus in patients with clear-cell mRCC progressing after first-line sunitinib or pazopanib. The primary end point was the number of patients without progression 6 months after starting everolimus. Secondary end points included progression-free survival (PFS), overall survival (OS), and overall response rate. Enrollment was terminated early due to slow recruitment; all analyses are descriptive. Results: Patients who received prior sunitinib (n = 16) or pazopanib (n = 13) were enrolled. One of 12 patients in the sunitinib group and 6/13 patients in the pazopanib group were progression-free by month 6 in the full analysis set. Median PFS in the sunitinib and pazopanib groups was 2.8 and 8.0 months, and median OS was 14.8 months and 20.4 months, respectively. Fifteen patients in the sunitinib group and 13 in the pazopanib group experienced adverse events. Conclusions: Safety and efficacy results confirm the second-line everolimus profile. However, baseline differences in patient populations should be taken into consideration. [ABSTRACT FROM AUTHOR]

Purpose: The field of immunotherapy combinations for advanced renal cell carcinoma (aRCC) has been expanded in recent years. However, the treatment response varies widely among individual patients. It is still a challenge to predict oncological outcome in clinical practice. We assessed the impact of an activated immune system reflected by changes in C-reactive protein (CRP) levels and the early onset of treatment-related adverse events (TRAEs) on the treatment response. Methods: In this retrospective analysis of 57 aRCC patients, CRP kinetics based on previous descriptions of CRP flare-response, CRP response or CRP non-response, and the TRAEs, which occurred within a month after therapy initiation, were obtained for this study. According to logistic regression analysis of both factors, we stratified the patients into risk groups: the presence of CRP flare-response/response and early onset of TRAE (low-risk group); the presence of a single factor (intermediate-risk group); and without both factors (high-risk group). Results: Ten patients (17%) experienced primary disease progression. No progressive disease was observed in the low-risk group, while 60% (n = 6/10) of the high-risk group showed a primary disease progression. Significantly, an increased risk of disease progression was observed by patients without CRP response and TRAEs (p < 0.001). Conclusion: The present analysis displays the predictive value of the on-treatment risk model based on CRP kinetics and the early onset of TRAEs, which can be easy to implement in clinical practice to optimize the treatment monitoring. [ABSTRACT FROM AUTHOR]

Abstract: Urine cytology is considered a valid diagnostic method of urological and nephrological diagnosis and follow-up, whereas immunohistochemistry is an indispensable adjunct to histopathology. The combination of both—urinary immunocytology—has, so far, only attained a marginal role. This review gives a state-of-the-art update of urinary markers and relevant epitopes, elucidates some methodological pitfalls, and gives an outlook on the promise of urinary immunocytology today. It suggests that morphological urine cytology should be amended by immunology in a mutual quest of urologists and pathologists to improve the diagnostic power of urine cytology. The cost-effectiveness of the method is considered. This review also sheds light on the age-old dispute among pathologists about the nature of urothelial carcinoma that is reflected in the frequent and controversial reclassifications of the disease. [Copyright &y& Elsevier]

Study Type - Therapy (individual cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Treatment recommendations such as interdisciplinary guidelines are always based on scientific publications. However, high-quality studies are very often focused on single-centre series of selected cases. Health care research has failed to provide comprehensive information that describes the clinical reality of prostate cancer management even in smaller centres. This is a health care research study with 17 participating centres. Any prostate cancer centre can use the internet-based database , at no additional cost, to collect and analyze data for quality management, to conduct consecutive follow-up assessments, and to compare their data with the averages recorded by all other centres. The database also enables time trend analysis of certain quality parameters in an annual comparison. OBJECTIVES • To report our experience with an Internet-based multicentre database that enables tumour documentation, as well as the collection of quality-related parameters and follow-up data, in surgically treated patients with prostate cancer. • The system was used to assess the quality of prostate cancer surgery and to analyze possible time-dependent trends in the quality of care. PATIENTS AND METHODS • An Internet-based database system enabled a standardized collection of treatment data and clinical findings from the participating urological centres for the years 2005-2009. • An analysis was performed aiming to evaluate relevant patient characteristics (age, pathological tumour stage, preoperative International Index of Erectile Function-5 score), intra-operative parameters (operating time, percentage of nerve-sparing operations, complication rate, transfusion rate, number of resected lymph nodes) and postoperative parameters (hospitalization time, re-operation rate, catheter indwelling time). • Mean values were calculated and compared for each annual cohort from 2005 to 2008. The overall survival rate was also calculated for a subgroup of the Berlin patients. RESULTS • A total of 914, 1120, 1434 and 1750 patients submitted to radical prostatectomy in 2005, 2006, 2007 and 2008 were documented in the database. • The mean age at the time of surgery remained constant (66 years) during the study period. • More than half the patients already had erectile dysfunction before surgery (median International Index of Erectile Function-5 score of 19-20). • During the observation period, there was a decrease in the percentage of pT2 tumours (1% in 2005; 64% in 2008) and a slight increase in the percentage of patients with lymph node metastases (8% in 2005; 10% in 2008). No time trend was found for the operating time (142-155 min) or the percentage of nerve-sparing operations (72-78% in patients without erectile dysfunction). • A decreasing frequency was observed for the parameters: blood transfusions (1.9% in 2005; 0.5% in 2008), postoperative bleeding (2.6%; 1.2%) and re-operations (4.5%; 2.8%). The mean hospitalization time decreased accordingly (10 days in 2005; 8 days in 2008). The examined subcohort had an overall mortality of 1.5% (median follow-up of 3 years). CONCLUSIONS • An Internet-based database system for tumour documentation in patients with prostate cancer enables the collection and assessment of important parameters for the quality of care and outcomes. • The participating centres show an improvement in the quality of surgical management, including a reduction of the complication rate. [ABSTRACT FROM AUTHOR]

Transperitoneal radical cystectomy with intraperitoneal ileal neobladder is the standard surgical treatment for muscle-invasive bladder cancer. To reduce morbidity, we established in 2002 an extraperitoneal approach including extraperitonealization of the ileal neobladder. This retrospective study compares the results of the two procedures with a focus on the peri- and postoperative course. Ninety-five male patients with invasive urothelial cancer who underwent radical cystectomy with ileal neobladder at our hospital from January 1998 to May 2007 were analyzed. Forty-seven patients underwent transperitoneal radical cystectomy with intraperitoneal ileal neobladder. The remaining 48 were submitted to the extraperitoneal technique with extraperitonealization of the neobladder. We compared both methods regarding operating time, intraoperative blood loss, complications and oncological outcome. The incidence of postoperative ileus was significantly lower after the extraperitoneal than after the transperitoneal approach (2/48 vs. 10/47 cases; p = 0.012). However, pelvic lymphoceles were more frequent (6 vs. 0 cases; p = 0.014). The two techniques did not differ with regard to the other major and minor complications, the operating time (mean 377.4 vs. 405.4 min) or the intraoperative blood loss (mean 363 vs. 412 ml). Oncological outcome disclosed no difference between both techniques. The extraperitoneal technique with extraperitonealization of the ileal neobladder is comparable in safety and reliability to the transperitoneal surgical approach and yields good peri- and postoperative results with regard to the parameters we examined. Noteworthy are the significant reduction of postoperative ileus and the higher incidence of lymphoceles. Both may be caused by the separate extraperitoneal regional healing processes. [ABSTRACT FROM AUTHOR]

OBJECTIVE To assess the course of cancer-free survival and thus determine how reliably reverse transcriptase-polymerase chain reaction (RT-PCR) can detect prostate-specific antigen (PSA)-expressing cells, as patients with untreated lymph node-positive prostate cancer tend to have a poor prognosis, whereas those treated with radical prostatectomy (RP) and immediate adjuvant hormonal therapy show excellent local disease control and a disease-free survival comparable with that of patients with negative lymph nodes, but the detection of micrometastatic disease in pelvic lymph nodes remains a major challenge. PATIENTS AND METHODS Quantitative RT-PCR was used to detect PSA mRNA expression in total RNA of 457 pelvic lymph nodes from 70 patients who had RP (53 patients) or laparoscopic lymphadenectomy (17) at our clinic in 1999/2000. For this purpose, alternate sections of lymph node tissue were either snap-frozen for later RNA isolation or examined by standard histopathological methods. Clinicopathological data, adjuvant treatments and follow-up data were recorded for all patients. RESULTS After January 2006 (6-year observation period), 13 patients had no follow-up data, while 27 had biochemical (PSA) recurrence or other evidence of clinical progression (two died from prostate cancer), and 30 had no signs of recurrence. Compared to the ‘reference’ standard (histopathology), the PCR method had a sensitivity of 83% and a specificity of 66%. The method had a positive predictive value of 52% and a negative predictive value of 57%. CONCLUSION Considered alone, pelvic lymph node PSA RT-PCR does not predict the clinical course better than a histopathological assessment of lymph nodes. However, it also identifies some patients with negative histology who later show progression. When added to the pathological classification, PSA RT-PCR improves the detection rate of primary lymphatic dissemination. [ABSTRACT FROM AUTHOR]

Abstract: Background: High-throughput gene expression profiling has recently shown that the mRNA for alpha-methylacyl CoA racemase (AMACR or P504S) is overexpressed in prostate carcinomas (PCa). Several immunohistochemical studies have reported the usefulness of anti-AMACR/P504S for detecting prostate cancer over the full range of prostate specimens encountered in surgical pathology. We tested real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for specific and sensitive detection of AMACR transcripts as a supplementary measure for discriminating between malignant and benign lesions in prostatic tissues. Methods: Total RNA was isolated from snap-frozen chips in 55 cases of benign prostatic hyperplasia (BPH) and from frozen sections in 57 prostatectomy cases. The latter were analyzed by an uropathologist (J.K.) and found to contain at least 50% malignant epithelia. Relative quantification of AMACR transcripts was performed by RT-PCR using hybridization probes for detection and PBGD for normalization. Results: Normalized AMACR transcript levels showed an average 3.75-fold increase in 57 prostate carcinomas cases when compared to 55 cases of BPH (p <0.0001). A 85.6% specificity and 64.9% sensitivity can be achieved if the cutoff is set at 12.95. AMACR expression levels among PCa cases were not statistically associated with the tumor and lymph node stage, the grading, the surgical margins, the Gleason score or progression. Discussion: The present study demonstrates the usefulness of quantitative AMACR-mRNA transcript detection in prostatic tissues as an alternative to immunological staining techniques. Since the latter clearly predominate in the laboratory routine, PCR-based detection of AMACR has the potential to gain widespread acceptance as a suitable future tool for monitoring prostate cancer patients. [Copyright &y& Elsevier]

To describe the effect of modifications to radical retropubic prostatectomy (RRP, known to be associated with severe bleeding) on blood loss in a retrospective analysis comparing RRPs by one experienced surgeon before and after the changes. The new method comprised reducing the intravenously applied volume, using a peridural catheter and maintaining a 25–30° Trendelenburg position. The difference in haemoglobin before and after RRP was analysed before the changes (group 1) and after (group 2). If transfusions were required the haemoglobin value was corrected, whereby 1 mL of erythrocyte concentrate increased the patient's haemoglobin by 0.03 g/L. Assessment was possible in 201 of 234 patients, 110 from group 1 and 91 from group 2. The mean transfusion-corrected difference in haemoglobin was 53 g/L in group 1 (20% transfusion rate) and 35.2 g/L in group 2 (1.09% transfusion rate; P > 0.001). The median intravenous volume applied was 5.96 L in group 1 and 3.49 L in group 2 ( P < 0.001). The complication rate did not differ between the groups. This new method minimizes the intraoperative blood loss during RRP; transfusions are only necessary in rare cases and the complication rate remained unaltered. [ABSTRACT FROM AUTHOR]

Purpose: Blunt abdominopelvic trauma frequently results in injuries to the urinary organs, especially in polytrauma. The urotrauma is rarely an acute life-threatening event; however, it may lead to severe complications. Methods: This review addresses the under-representation of urological trauma management in interdisciplinary medical training and its impact on patient outcomes. It compiles evidence-based recommendations and guidelines from multiple specialties, focusing on common challenges in managing these injuries. The resource is tailored for primary care physicians in radiology, trauma surgery, internal medicine, urology, and nephrology. Results: Urinary tract injuries can occur even if the patient's condition initially appears normal. An exclusion diagnosis is obligatory by contrast medium tomography of the entire urinary tract and, if suspected, an additional uroendoscopic examination. Interventional therapy by catheterisation of the urinary tract is often required. Urosurgical treatment is not commonly needed, but when there is a demand, it must be administered via an interdisciplinary approach with visceral and trauma surgery. Over 90% of life-threatening kidney injuries (usually up to grade 4–5 AAST) are presently treated by interventional radiologists. Acute kidney injury (AKI) as a complication in trauma patients may complicate clinical management and often worsens the outcome. The incidence of trauma-associated AKI in patients admitted to an intensive care unit is high. Conclusions: Patients suffering from blunt abdominopelvic trauma should ideally be referred to certified trauma centres with subspecialised or fully specialised care provided by visceral/vascular surgery, trauma surgery, interventional radiology, urology, and nephrology. This recommendation is based on the complex nature of most damage patterns. [ABSTRACT FROM AUTHOR]

To demonstrate the added benefit of multiparametric (mp)MRI risk stratification during active surveillance. This prospective, single-arm, nonrandomized study included 82 men with low-risk prostate cancer (PCa). We compared two biopsy strategies in parallel. The first biopsy strategy was an in-bore and transrectal ultrasound (TRUS) biopsy in men with suspicious mpMRI findings. The second was a TRUS biopsy in all 82 men, blinded to the results of the previously performed mpMRI. We identified 27/82 men with suspicious mpMRI. Of those 27 men, we detected 8/27 with csPCa on biopsy, and we identified two men with in-bore biopsy exclusively, three men with TRUS biopsy exclusively, and three men with both biopsy strategies. Of the 55/82 men with nonsuspicious mpMRI (who only received TRUS biopsies), two men had csPCa. TRUS biopsy of the entire cohort of 82 men would have led to the correct diagnosis of 80% men with csPCa, requiring all 82 men to receive biopsies (csPCa in 10% of the 82 biopsies). Conducting in-bore biopsies plus TRUS biopsies in men with suspicious mpMRI would have also led to the detection of 80% of men with csPCa, requiring only 27 men to receive biopsies (csPCa in 30% of the 27 biopsies). The combination of TRUS and in-bore biopsies, limited to men with suspicious mpMRI, resulted in a similar detection rate of csPCa compared to TRUS biopsies of all men but required only one-third of men to undergo biopsy. Our results indicate that in-bore and TRUS biopsies continue to complement each other. [ABSTRACT FROM AUTHOR]

For patients with metastatic renal cell carcinoma who received tyrosine kinas inhibitor (TKI) induction therapy, a switch to nivolumab for maintenance therapy had lower efficacy than TKI continuation. Our study indicates that patients who respond to a TKI should continue treatment. Future studies should explore the role of biomarkers to guide therapy selection. The role of immune checkpoint inhibitor (ICI) maintenance therapy in metastatic renal cell carcinoma (mRCC) is undefined. To determine whether switch maintenance therapy with nivolumab improves clinical outcomes in patients with mRCC with tyrosine kinase inhibitor (TKI) sensitivity. This open-label phase 2 trial randomized patients with a partial response or stable disease after 10–12-wk TKI induction therapy to either TKI or nivolumab maintenance. Key inclusion criteria were measurable disease, clear cell histology, Eastern Cooperative Oncology Group performance status (ECOG PS) 0–2, and adequate organ function. Intravenous nivolumab 8 × 240 mg every 2 wk, followed by 480 mg every 4 wk or sunitinib 50 mg (4–2 regimen) or pazopanib 800 mg once daily orally. The primary endpoint was overall survival (OS). Secondary endpoints were the objective response rate (ORR; Response Evaluation Criteria in Solid Tumors v1.1), progression-free survival (PFS), safety (Common Terminology Criteria for Adverse Events v4.03), and patient-reported outcomes (Functional Assessment of Cancer Therapy Kidney Symptom Index). The Kaplan-Meier method, two-sided log-rank tests, and Cox regression models were used for statistical analysis. Maintenance therapy was nivolumab for 25 patients (51.0%) and TKI for 24 (48.9%). The median age was 65 yr (range 35–79). Nine patients (18.4%) were female, 31 (63.3%) had ECOG PS of 0, and 15 (30.6%) had favorable risk. OS data are immature (17 deaths, 34.7%). The ORR was 20.0% (n = 5) for nivolumab and 52.2% (n = 12) for TKI. PFS was worse with nivolumab (hazard ratio 2.57, 95% confidence interval 1.36–4.89; p = 0.003). Grade ≥3 adverse events occurred in 14 patients (56.0%) with nivolumab and 17 (70.8%) with TKI. A major limitation is early termination of our study. TKI treatment achieved superior ORR and PFS in comparison to nivolumab maintenance therapy. Our data do not indicate a role for nivolumab switch maintenance in mRCC. Patients with metastatic kidney cancer who experienced a tumor response or disease stabilization after a short period of targeted treatment with a tyrosine kinase inhibitor did not benefit from a switch to the immunotherapy drug nivolumab. Patients who continued their original treatment achieved better responses and a longer time without disease progression. This trial is registered on EudraCT as 2016-002170-13 and on ClinicalTrials.gov as NCT02959554. [ABSTRACT FROM AUTHOR]

Purpose: To determine oncological and functional outcomes and side effects after focal therapy of prostate cancer (PCa) with high-intensity focused ultrasound (HIFU). Methods: This retrospective single-center study included 57 consecutive patients with localised PCa. Aged 18–80 with ≤2 suspicious lesions on mpMRI (PIRADS ≥ 3), PSA of ≤15 ng/mL, and an ISUP GG of ≤2. HIFU was performed between November 2014 and September 2018. All men had an MRI/US fusion-guided targeted biopsy (TB) combined with a TRUS-guided 10-core systematic biopsy (SB) prior to focal therapy. HIFU treatment was performed as focal, partial, or hemiablative, depending on the prior histopathology. Follow-up included Questionnaires (IIEF-5, ICIQ, and IPSS), prostate-specific antigen (PSA) measurement, follow-up mpMRI, and follow-up biopsies. Results: The median age of the cohort was 72 years (IQR 64–76), and the median PSA value before HIFU was 7.3 ng/mL (IQR 5.75–10.39 ng/mL). The median follow-up was 27.5 (IQR 23–41) months. At the time of the follow-up, the median PSA value was 2.5 ng/mL (IQR 0.94–4.96 ng/mL), which shows a significant decrease (p < 0.001). In 17 (29.8%) men, mpMRI revealed a suspicious lesion, and 19 (33.3%) men had a positive biopsy result. Only IIEF values significantly decreased from 16 (IQR 10.75–20.25) to 11.5 (IQR 4.5–17) (p < 0.001). The rate of post-HIFU complications was low, at 19.3% (11 patients). The limitation of this study is the lack of long-term follow-up. Conclusions: HIFU as a therapy option for nonmetastatic, significant prostate cancer is effective in the short term for carefully selected patients and shows a low risk of adverse events and side effects. [ABSTRACT FROM AUTHOR]

Nivolumab is used after platinum-based chemotherapy in patients with metastatic urothelial carcinoma. Studies suggest improved outcomes for dual checkpoint inhibition with high ipilimumab doses. We aimed to examine the safety and activity of nivolumab induction and high-dose ipilimumab as an immunotherapeutic boost as a second-line treatment for patients with metastatic urothelial carcinoma. TITAN-TCC is a multicentre, single-arm, phase 2 trial done at 19 hospitals and cancer centres in Germany and Austria. Adults aged 18 years or older with histologically confirmed metastatic or surgically unresectable urothelial cancer of the bladder, urethra, ureter, or renal pelvis were eligible. Patients had to have progression during or after first-line platinum-based chemotherapy and up to one more second-line or third-line treatment, a Karnofsky Performance Score of 70 or higher, and measurable disease as per Response Evaluation Criteria in Solid Tumors version 1.1. After four doses of intravenous nivolumab 240 mg induction monotherapy every 2 weeks, patients with a partial or complete response at week 8 continued maintenance nivolumab, whereas those with stable or progressive disease (non-responders) at week 8 received a boost of two or four doses of intravenous nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks. Patients who subsequently had progressive disease during nivolumab maintenance also received a boost, using this schedule. The primary endpoint was the confirmed investigator-assessed objective response rate in the intention-to-treat population and had to exceed 20% for the null hypothesis to be rejected (based on the objective response rate with nivolumab monotherapy in the CheckMate-275 phase 2 trial). This study is registered with ClinicalTrials.gov , NCT03219775 , and is ongoing. Between April 8, 2019, and Feb 15, 2021, 83 patients with metastatic urothelial carcinoma were enrolled and all received nivolumab induction treatment (intention-to-treat population). The median age of enrolled patients was 68 years (IQR 61–76), and 57 (69%) were male and 26 (31%) were female. 50 (60%) patients received at least one boost dose. A confirmed investigator-assessed objective response was recorded in 27 (33%) of 83 patients in the intention-to-treat population, including six (7%) patients who had a complete response. This objective response rate was significantly higher than the prespecified threshold of 20% or less (33% [90% CI 24–42]; p=0·0049). The most common grade 3–4 treatment-related adverse events were immune-mediated enterocolitis (nine [11%] patients) and diarrhoea (five [6%] patients). Two (2%) treatment-related deaths were reported, both due to immune-mediated enterocolitis. Treatment with nivolumab and nivolumab plus ipilimumab boosts in early non-responders and patients who progress late significantly improved objective response rate after previous platinum-based chemotherapy compared with the rate reported with nivolumab in the CheckMate-275 trial. Our study provides evidence for the added value of high-dose ipilimumab 3 mg/kg and suggests a potential role for the combination as a rescue strategy in platinum-pretreated patients with metastatic urothelial carcinoma. Bristol Myers Squibb. [ABSTRACT FROM AUTHOR]

In patients with prostate-specific antigen doubling time >6–≤10 mo who are at a risk of progression to metastatic disease, darolutamide significantly improved metastasis-free survival, overall survival, and other patient-relevant endpoints versus placebo, without undue toxicity burden or adversely affecting health-related quality of life. Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) have a high risk of progression to metastatic disease, particularly if their prostate-specific antigen doubling time (PSADT) is ≤6 mo. However, patients remain at a high risk with a PSADT of >6 mo. To evaluate the efficacy and safety of darolutamide versus placebo in patients stratified by PSADT >6 or ≤6 mo. A planned subgroup analysis of a global multicenter, double-blind, randomized, phase 3 trial in men with nmCRPC and PSADT ≤10 mo was conducted. Patients were randomized 2:1 to oral darolutamide 600 mg twice daily or placebo, while continuing androgen-deprivation therapy. The primary endpoint was metastasis-free survival (MFS). Secondary endpoints were overall survival (OS) and times to pain progression, first cytotoxic chemotherapy, and symptomatic skeletal events. Quality of life (QoL) was measured using validated prostate-relevant tools. Safety was recorded throughout the study. Of 1509 patients enrolled, 469 had PSADT >6 mo (darolutamide n = 286; placebo n = 183) and 1040 had PSADT ≤6 mo (darolutamide n = 669; placebo n = 371). Baseline characteristics were balanced between subgroups. Darolutamide significantly prolonged MFS versus placebo in both subgroups (unstratified hazard ratio [95% confidence interval]: PSADT >6 mo, 0.38 [0.26–0.55]; PSADT ≤6 mo, 0.41 [0.33–0.52]). OS and other efficacy and QoL endpoints favored darolutamide with significant improvement over placebo in both subgroups. The incidence of adverse events, including events commonly associated with androgen receptor inhibitors (fractures, falls, hypertension, and mental impairment), and discontinuations due to adverse events were low and similar to placebo. Limitations include small subgroup populations. In patients with nmCRPC and PSADT >6 mo (maximum 10 mo), darolutamide provided a favorable benefit/risk ratio, characterized by significant improvements in MFS, OS, and other clinically relevant endpoints; maintenance of QoL; and favorable tolerability. In patients with prostate cancer that has stopped responding to standard hormonal therapy (indicated by an increase in prostate-specific antigen [PSA] levels), there is a risk that the cancer will spread to other parts of the body. This risk is highest when the time it takes for the PSA level to double (ie, "PSA doubling time" [PSADT]) is less than 6 mo. However, there is still a risk that the cancer will spread even if the PSADT is longer than 6 mo. In a group of patients whose PSADT was more than 6 mo but no more than 10 mo, treatment with darolutamide slowed the cancer spread and allowed them to live longer than patients who received placebo (inactive drug). Darolutamide treatment did not cause many side effects and helped maintain patients' quality of life without disruptions. [ABSTRACT FROM AUTHOR]

Simple Summary: Clinical trials have demonstrated the effectiveness of pazopanib as a primary treatment for metastatic renal cell carcinoma (mRCC). The approval of tyrosine kinase inhibitors and checkpoint-inhibitors represented further progress in the mRCC treatment landscape. Yet, with the recent changes in treatment options, there are scarce real-world data on these substances, including pazopanib. The PAZOREAL study investigated the effectiveness and safety of pazopanib (first-line), nivolumab (second-line), and everolimus (second- and third-line) in a real-life setting. This study included 376 mRCC patients who received first-line treatment with pazopanib and assessed the treatment's effectiveness, safety, and resultant quality of life. The median time on the drug for the study population was 10.0 months; for primary treatment with pazopanib, it was 6.3 months. The median overall survival (mOS) for the entire study population was 35.9 months. No new safety signals were detected. PAZOREAL provides valuable real-world data for the primary treatment of mRCC with pazopanib. The approval of tyrosine kinase inhibitors and checkpoint inhibitors represented a remarkable progression in the therapeutic landscape for the treatment of metastatic renal cell carcinoma (mRCC). Yet, in the ever-evolving landscape of mRCC treatment, real-world data on these agents, including pazopanib, are scarce. The non-interventional PAZOREAL study investigated the effectiveness and safety of pazopanib (first-line), nivolumab (second-line), and everolimus (second- and third-line) in a real-life setting. The multicentric study included 376 mRCC patients who received first-line treatment with pazopanib and assessed time on the drug (primary endpoint), overall survival, best responses, disease control rates, as well as safety signals and health-related quality of life. The median overall time on the drug was 10.0 months, with first-line pazopanib having a median time on drug of 6.3 months. The median overall survival was 35.9 months. The disease control rate for first-line pazopanib was 56.9%. No new safety signals were detected. PAZOREAL provides valuable real-world data for first-line treatment with pazopanib. [ABSTRACT FROM AUTHOR]

Objective: To assess the potential for molecular staging in biopsies of the prostatic fossa after radical prostatectomy (RP) by searching for occult tumour cells through analysis of glutathione S‐transferase P1 (GSTP1) methylation status. Patients and Methods: We analysed 2446 biopsies: 2286 biopsies from a group of 254 patients with clinically organ‐confined prostate cancer who underwent RP and 160 biopsies from a control group of 32 patients. After prostate gland excision, biopsies were obtained from defined areas of the prostatic fossa and bisected for histopathological and molecular genetics analyses. Results were related to clinicopathological data including tumour stage, lymph node status, resection status, tumour grading, initial PSA level, and biochemical recurrence. Results: In total, 34 patients (13.4%) had at least one core positive for the GSTP1 promoter hypermethylation, six of whom (17.6%) were characterised as having a clinically localised tumour stage (pT2, pN0) and 28 (82.4%) as an advanced tumour stage (≥pT3 and/or pN1). GSTP1 promoter hypermethylation significantly correlated with tumour stage (P < 0.001), International Society of Urological Pathology grading (P = 0.001), lymph node status (P < 0.001), surgical margin status (P < 0.001), and biochemical recurrence (P = 0.001). Furthermore, in 46 patients (18.1%) further analysis led to a down‐ or upgrading of conventional surgical margin status. Classical R‐status (margins of the specimen) is significantly superior to histological sampling from the fossa (P = 0.006) but not to GSTP1 analysis from the fossa (P = 0.227). Conclusion: For the detection of residual tumour in the fossa after RP in order to better predict recurrence, molecular GSTP1 promoter hypermethylation has some value; however, the classical R‐status (margins of the specimen) is simpler and more widely applicable with similar results. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging/Ultrasound (MRI/US) fusion targeted biopsy (TB) in combination with a systematic biopsy (SB) improves cancer detection but limited data is available how to manage patients with a Prostate Imaging-Reporting and Data System (PI-RADS) ≥ 4 lesion and a negative biopsy. We evaluate the real-world management and the rate of clinically significant Prostate Cancer (csPCa) during follow-up. 1546 patients with a multi-parametric MRI (mpMRI) and a PI-RADS ≥ 3 who underwent SB and TB between January 2012 and May 2017 were retrospectively analyzed. 222 men with a PI-RADS ≥ 4 and a negative biopsy were included until 2019. For 177/222 (80%) complete follow-up data was obtained. 66/84 (78%) had an initial PI-RADS 4 and 18 (22%) a PI-RADS 5 lesion. 48% (84/177) received a repeat mpMRI; in the follow-up mpMRI, 39/84 (46%) lesions were downgraded to PI-RADS 2 and 11 (13%) to PI-RADS 3; three cases were upgraded and 28 lesions remained consistent. 18% (32/177) men underwent repeated TB and csPCa was detected in 44% (14/32). Our study presents real world data on the management of men with a negative TB biopsy. Men with a positive mpMRI and lesions with high suspicion (PI-RADS4/5) and a negative targeted biopsy should be critically reviewed and considered for repeat biopsy or strict surveillance. The optimal clinical risk assessment remains to be further evaluated. [ABSTRACT FROM AUTHOR]

Purpose: Due to the tissue preserving approach of focal therapy (FT), local cancer relapse can occur. Uncertainty exists regarding triggers and outcome of salvage strategies. Methods: Patients with biopsy-proven prostate cancer (PCa) after FT for localized PCa from 2011 to 2020 at eight tertiary referral hospitals in Germany that underwent salvage radical prostatectomy (S-RP), salvage radiotherapy (S-RT) or active surveillance (AS) were reported. Prostate specific antigen (PSA) changes, suspicious lesions on mpMRI and histopathological findings on biopsy were analyzed. A multivariable regression model was created for adverse pathological findings (APF) at S-RP specimen. Kaplan–Meier curves were generated to determine oncological outcomes. Results: A total of 90 men were included. Cancer relapse after FT was detected at a median of 12 months (IQR 9–16). Of 50 men initially under AS 13 received S-RP or S-RT. In total, 44 men underwent S-RP and 13 S-RT. At cancer relapse 17 men (38.6%) in the S-RP group [S-RT n = 4 (30.8%); AS n = 3 (6%)] had ISUP > 2. APF (pT ≥ 3, ISUP ≥ 3, pN + or R1) were observed in 23 men (52.3%). A higher ISUP on biopsy was associated with APF [p = 0.006 (HR 2.32, 97.5% CI 1.35–4.59)] on univariable analysis. Progression-free survival was 80.4% after S-RP and 100% after S-RT at 3 years. Secondary therapy-free survival was 41.7% at 3 years in men undergoing AS. Metastasis-free survival was 80% at 5 years for the whole cohort. Conclusion: With early detection of cancer relapse after FT S-RP and S-RT provide sufficient oncologic control at short to intermediate follow-up. After AS, a high secondary-therapy rate was observed. [ABSTRACT FROM AUTHOR]

Background: Epidermal Growth Factor Receptor is often overexpressed in advanced prostate carcinoma. In-vitro-studies in prostate carcinoma cell line DU145 have demonstrated increased sensibility to radiation after cetuximab treatment, but clinical data are not sufficient to date.Methods: We analyzed effects of radiation and cetuximab in DU145 and A431 using proliferation, colony-forming-unit- and annexin-V-apoptosis-assays. Changes in protein expression of pEGFR and pERK1/2 after radiation and cetuximab treatment were analyzed. Using NGS we also investigated the impact of cetuximab long-term treatment.Results: Cell counts in DU145 were reduced by 44% after 4 Gy (p = 0.006) and 55% after 4 Gy and cetuximab (p < 0.001). The surviving fraction (SF) was 0.69 after 2 Gy, 0.41 after 4 Gy and 0.15 after 6 Gy (each p < 0.001). Cetuximab treatment did not alter significantly growth reduction in 4 Gy radiated DU145 cells, p > 0.05 or SF, p > 0.05, but minor effects on apoptotic cell fraction in DU145 were detected. Using western blot, there were no detectable pEGFR and pERK1/2 protein signals after cetuximab treatment. No RAS mutation or HER2 amplification was detected, however a TP53 gen-mutation c.820G > T was found.Conclusions: Radiation inhibits cell-proliferation and colony-growth and induces apoptosis in DU145. Despite blocking MAP-Kinase-pathway using cetuximab, no significant radiation-sensitizing-effect was detected. Cetuximab treatment did not induce resistance-mutations. Further research must clarify which combination of anti-EGFR treatment strategies can increase radiation-sensitizing-effects. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies have shown that prestenting in ureterorenoscopic stone removal (URS) is carried out more frequently in Germany than in other countries. Objective: This investigation evaluated the impact of high prestenting rates on outcomes as well as the influence of stone characteristics and treatment habits on prestenting. Methods: The dataset from the BUSTER observational study was used. Patient and stone characteristics, as well as treatment outcomes, were analyzed for 307 cases from 14 urological clinics in Germany. Results: The overall prestenting rate was 70.0%. Prestenting rates were significantly higher for renal stones than ureteric stones (84.6 vs. 60.6%, p < 0.0001). Compared to the unstented cases, prestenting for renal stones improved stone-free rates (73.2 vs. 11.1%, p < 0.0001) and increased the rate of completely lesion-free URS (45.4 vs. 16.7%, p = 0.034) while reducing the rate of poststenting (from 100 to 80.8%, p = 0.041). None of these effects could be demonstrated when prestenting for ureteric stones. Prestenting rates were less variable for renal stones (57–100%) than for ureteric stones (0–100%, p < 0.01). Conclusions: This study confirms the benefits of prestenting in URS for renal stones but not for ureteric stones. There were considerable differences in prestenting rates between the participating clinics. [ABSTRACT FROM AUTHOR]

Objectives: We investigated the diagnostic efficacy of the prostate health index (PHI) and PHI density (PHID) to avoid unnecessary prostate biopsies in 3 urological practices. Methods: In 122 patients, total prostate-specific antigen (PSA), free PSA (f-PSA), the quotient from total PSA and f-PSA (f-PSA%), and [–2]pro-PSA were measured in the serum; PHI, PHID, and PSA density (PSAD) were calculated prior to prostate biopsy. Tissue sampling via transrectal biopsy was indicated in case of suspicious PSA (progression and/or elevation of PSA) and/or suspicious digital rectal examination. PSAD, PHI, and PHID were not used for biopsy indication. The diagnostic efficacy was determined with receiver-operating characteristic (ROC)and decision curve analyses. Results: Based on prostate biopsies, 38% (n = 46) of the cases had no prostate carcinoma (PCa), 21% (n = 26) no clinically significant (insignificant) PCa, and 41% (n = 50) had clinically significant PCa. ROC analyses of the PSA parameters showed higher diagnostic efficacy for PHI and PHID (AUC 0.722 and 0.739) than for f-PSA%, PSA, and PSAD (AUC 0.612, 0.595, and 0.698, respectively) regarding carcinoma diagnosis. With a combined use of PHI and PHID (cutoff >40 and >0.9, respectively), only 1 clinically significant PCa would have been missed (sensitivity 98%); in 24 (20%) patients, biopsy could have been avoided. Conclusion:The integration of PHI and PHID could improve the diagnostic efficacy of risk calculators to avoid unnecessary prostate biopsies. However, as a prerequisite, validation of cutoff values in prospective studies is urgently required. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to establish the setup and workflow for delivering focal MRI-guided high-dose-rate (HDR) brachytherapy for prostate cancer (PCA) and to assess patient comfort and safety aspects of MRI-guided single-fraction HDR.Methods: Patients with histologically proven focal low- to intermediate-risk PCA with a single PIRADS 4/5 lesion were treated with percutaneous interstitial HDR brachytherapy in a single fraction with a minimum dose for the gross tumor volume of 20 Gy while sparing the organ at risk (OAR). Using a 3T-MRI, brachytherapy catheters were placed transgluteal in freehand technique. No antibiotic therapy or general analgesics were administered. Patient data, procedure time, patient discomfort, and complications were recorded. Quarterly PSA controls, biannual follow-up imaging, and annual re-biopsy were planned.Results: So far, 9 patients were successfully treated and followed for 6 months. Mean intervention time was 34 min. Using the VAS scale, the pain reported for the intervention ranged from 2 to 3. Short-term follow-up showed no acute genitourinary or gastrointestinal toxicity so far. None of the patients displayed signs of infection. PSA levels in all patients decreased significantly. On follow up no residual PCA was detected treated region so far. PSA levels in all patients decreased significantly. On follow-up, no residual PCA was detected so far.Conclusions: MR-guided single-fraction focal HDR brachytherapy for localized PCA is feasible as well as safe for the individual patient. Catheters can be placed accurately and maximum therapeutic dose distribution can be restricted to the tumor. Countersigning the minimally invasive character of the procedure, no general anesthesia or antibiosis is necessary.Key Points: • MR-guided focal HDR brachytherapy allows an accurate placement of catheters with maximum therapeutic dose distribution restricted to the tumor. • No major anesthesia or antibiosis is necessary emphasizing the minimal invasive character of the procedure. • Patients with low- and intermediate-risk prostate carcinoma in particular may benefit to halt disease progression whereas treatment-related morbidity is reduced compared with radical therapy. [ABSTRACT FROM AUTHOR]

Background: The clinical activity of fibroblast growth factor receptor (FGFR) inhibitors seems restricted to cancers harbouring rare FGFR genetic aberrations. In preclinical studies, high tumour FGFR mRNA expression predicted response to rogaratinib, an oral pan-FGFR inhibitor. We aimed to assess the safety, maximum tolerated dose, recommended phase 2 dose, pharmacokinetics, and preliminary clinical activity of rogaratinib.Methods: We did a phase 1 dose-escalation and dose-expansion study of rogaratinib in adults with advanced cancers at 22 sites in Germany, Switzerland, South Korea, Singapore, Spain, and France. Eligible patients were aged 18 years or older, and were ineligible for standard therapy, with an Eastern Cooperative Oncology Group performance status of 0-2, a life expectancy of at least 3 months, and at least one measurable or evaluable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. During dose escalation, rogaratinib was administered orally twice daily at 50-800 mg in continuous 21-day cycles using a model-based dose-response analysis (continuous reassessment method). In the dose-expansion phase, all patients provided an archival formalin-fixed paraffin-embedded (FFPE) tumour biopsy or consented to a new biopsy at screening for the analysis of FGFR1-3 mRNA expression. In the dose-expansion phase, rogaratinib was given at the recommended dose for expansion to patients in four cohorts: urothelial carcinoma, head and neck squamous-cell cancer (HNSCC), non-small-cell lung cancer (NSCLC), and other solid tumour types. Primary endpoints were safety and tolerability, determination of maximum tolerated dose including dose-limiting toxicities and determination of recommended phase 2 dose, and pharmacokinetics of rogaratinib. Safety analyses were reported in all patients who received at least one dose of rogaratinib. Patients who completed cycle 1 or discontinued during cycle 1 due to an adverse event or dose-limiting toxicity were included in the evaluation of recommended phase 2 dose. Efficacy analyses were reported for all patients who received at least one dose of study drug and who had available post-baseline efficacy data. This ongoing study is registered with ClinicalTrials.gov, number NCT01976741, and is fully recruited.Findings: Between Dec 30, 2013, and July 5, 2017, 866 patients were screened for FGFR mRNA expression, of whom 126 patients were treated (23 FGFR mRNA-unselected patients in the dose-escalation phase and 103 patients with FGFR mRNA-overexpressing tumours [52 patients with urothelial carcinoma, eight patients with HNSCC, 20 patients with NSCLC, and 23 patients with other tumour types] in the dose-expansion phase). No dose-limiting toxicities were reported and the maximum tolerated dose was not reached; 800 mg twice daily was established as the recommended phase 2 dose and was selected for the dose-expansion phase. The most common adverse events of any grade were hyperphosphataemia (in 77 [61%] of 126 patients), diarrhoea (in 65 [52%]), and decreased appetite (in 48 [38%]); and the most common grade 3-4 adverse events were fatigue (in 11 [9%] of 126 patients) and asymptomatic increased lipase (in 10 [8%]). Serious treatment-related adverse events were reported in five patients (decreased appetite and diarrhoea in one patient with urothelial carcinoma, and acute kidney injury [NSCLC], hypoglycaemia [other solid tumours], retinopathy [urothelial carcinoma], and vomiting [urothelial carcinoma] in one patient each); no treatment-related deaths occurred. Median follow-up after cessation of treatment was 32 days (IQR 25-36 days). In the expansion cohorts, 15 (15%; 95% CI 8·6-23·5) out of 100 evaluable patients achieved an objective response, with responses recorded in all four expansion cohorts (12 in the urothelial carcinoma cohort and one in each of the other three cohorts), and in ten (67%) of 15 FGFR mRNA-overexpressing tumours without apparent FGFR genetic aberration.Interpretation: Rogaratinib was well tolerated and clinically active against several types of cancer. Selection by FGFR mRNA expression could be a useful additional biomarker to identify a broader patient population who could be eligible for FGFR inhibitor treatment.Funding: Bayer AG. [ABSTRACT FROM AUTHOR]

Introduction: Intraoperative software assistance is gaining increasing importance in laparoscopic and robot-assisted surgery. Within the user-centred development process of such systems, the first question to be asked is: What information does the surgeon need and when does he or she need it? In this article, we present an approach to investigate these surgeon information needs for minimally invasive partial nephrectomy and compare these needs to the relevant surgical computer assistance literature. Materials and methods: First, we conducted a literature-based hierarchical task analysis of the surgical procedure. This task analysis was taken as a basis for a qualitative in-depth interview study with nine experienced surgical urologists. The study employed a cognitive task analysis method to elicit surgeons' information needs during minimally invasive partial nephrectomy. Finally, a systematic literature search was conducted to review proposed software assistance solutions for minimally invasive partial nephrectomy. The review focused on what information the solutions present to the surgeon and what phase of the surgery they aim to support. Results: The task analysis yielded a workflow description for minimally invasive partial nephrectomy. During the subsequent interview study, we identified three challenging phases of the procedure, which may particularly benefit from software assistance. These phases are I. Hilar and vascular management, II. Tumour excision, and III. Repair of the renal defects. Between these phases, 25 individual challenges were found which define the surgeon information needs. The literature review identified 34 relevant publications, all of which aim to support the surgeon in hilar and vascular management (phase I) or tumour excision (phase II). Conclusion: The work presented in this article identified unmet surgeon information needs in minimally invasive partial nephrectomy. Namely, our results suggest that future solutions should address the repair of renal defects (phase III) or put more focus on the renal collecting system as a critical anatomical structure. [ABSTRACT FROM AUTHOR]

Summary: Background: Despite the high utilisation of ureterorenoscopy (URS) in interventional stone treatment, there is little evidence of any link between annual hospital volume and outcome. Methods: From January to April 2015, data from 307 URS patients were prospectively recorded in the multicentre observational BUSTER-Trial (Benchmarks of ureterorenoscopic stone treatment-results in terms of complications, quality of life, and stone-free rates). The best threshold value for annual hospital volume with an independent effect on the outcome (measured on stone-free and complication rates) of our study group was established with logistic regression. Results: In 38.4% of cases of renal and 61.6% of ureteral stones, median stone size was 6 mm with an interquartile range (IQR) of 4–8 mm. The annual URS rate in the 14 participating hospitals ranged from 77 to 333 (median 144; IQR 109–208). The binary endpoint as a combination of completely stone-free or residual fragments small enough to pass spontaneously and a maximum complication severity of Clavien–Dindo grade 1 was attained in 234/252 (92.9%) cases with a hospital volume of ≥ 99 URS compared with 43/55 (78.2%) in < 99 URS (p = 0.002). Adjusted for patient-, stone- and physician-related factors, an annual hospital URS volume of ≥ 99 increases the chance of an optimum outcome (OR = 3.92; 95% CI 1.46–10.51; p = 0.007). Conclusions: An independent effect of URS hospital volume on outcome quality in the 14 participating hospitals was demonstrated. Threshold values for annual case numbers should be scientifically established irrespective of the considered procedure. [ABSTRACT FROM AUTHOR]

Background: The Post-Ureteroscopic Lesion Scale (PULS) is a validated, standardised scale that classifies iatrogenic ureteral lesions during ureteroscopy (URS). Objective: To determine risk factors for the various PULS-grades caused by URS. Method: We prospectively investigated the independent influence of various risk factors in correlation with PULS-Grade 1+ and 2+ on 307 patients with ureterorenoscopic stone treatment from 14 German urologic departments. Results: The following are the outcomes of the study: 117 (38.4%) and 188 (61.6%) of the calculi (median stone size 6 mm) were found in the kidney or ureter; 70% and 82.4% underwent preoperative or postoperative ureteral stenting; 44.3 and 7.2% received laser or ballistic lithotripsy; 60% of the patients presented with PULS grade 1+ and 8% with PULS grade of 2+. Only intracorporal lithotripsy revealed a significant independent risk factor for PULS grade 1+ or 2+. Both laser and ballistic therapies raised the probability of PULS grade 1+ by the factors 3.6 (p < 0.001) and 3.9 (p = 0.021), respectively. The ORs in conjunction with PULS grade 2+ were 3.1 (p = 0.038) and 5.8 (p = 0.014) respectively. Neither endpoint exhibited a significant difference regarding the lithotripsic procedure (laser vs. ballistic). Conclusion: Intracorporal lithotripsy is associated with a significant increase in damage to the ureter; further research is needed to determine its long-term effects. [ABSTRACT FROM AUTHOR]

Objective: The aim of our study was (1) to establish an in-bore targeted biopsy of suspicious prostate lesions, avoiding bowel penetration using a transgluteal approach and (2) to assess operator setup, patient comfort and safety aspects in the clinical setting for freehand real-time MR-guidance established for percutaneous procedures in an open MR-scanner.Material and Methods: 30 patients with suspect prostate lesions were biopsied in a cylindrical 3T-MRI system using a transgluteal approach in freehand technique. One to three biopsies were sampled using continuous dynamic imaging. Size, location and visibility of the lesion, intervention time, needle artefact size, interventional complications and histopathological diagnosis were recorded.Results: All biopsies were technically successful. Nineteen patients showed evidence of prostate carcinoma. Cancer detection rate was 50 % in patients with previously negative TRUS-biopsy. The average intervention time was 26 min including a learning curve as the time was 13 min by the end of the study. No antibiotic prophylaxis was performed as none of the patients showed signs of infection.Conclusions: MR-guided targeted freehand biopsies of prostate lesions using a transgluteal approach are both technically feasible and time efficient in a standard closed-bore 3T-MR scanner as well as safe for the individual patient.Key Points: • Open-bore freehand interventional principles were adapted to closed-bore systems. • Prostate MR-guided freehand biopsies were feasible in a clinical setting. • A transgluteal approach provides a short and simplified work flow. • An inoculation of the prostate with bowel flora is avoided. • The intervention time is comparable to the stereotactic approach. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy of irreversible electroporation (IRE) ablation of pT1a renal cell carcinoma (RCC) in the first prospective, monocentric phase 2a pilot ablate-and-resect study (Irreversible Electroporation of Kidney Tumors Before Partial Nephrectomy [IRENE] trial). It has been postulated that focal IRE can bring about complete ablation of soft-tissue tumors with protection of healthy peritumoral tissue and anatomic structures.Patients and Methods: The first 7 study patients with biopsy-proven pT1a RCC (15-39 mm) underwent IRE. Percutaneous computed tomography-guided IRE was performed with electrocardiographic triggering under general anesthesia and deep muscle paralysis with 3-6 monopolar electrodes positioned within the renal tumor. Twenty-eight days later, the tumor region was completely resected to confirm tumor destruction pathologically. Individual results for these patients are displayed, described, and discussed.Results: Technical feasibility was attained in all patients, but electrode placement and ablation were complex, with a mean overall procedure time of 129 minutes. There were no major complications. Partial kidney resection was performed in 5 patients, and radical nephrectomy was performed in 2 patients because of central tumor location and ablation areas. Resections revealed by tumor, node, and metastasis classification of the International Union for Cancer Control 2017 no residual tumor as complete ablation in 4 cases (ypT0V0N0Pn0R0) and microscopic residual tumor cells as incomplete ablation in the other 3 cases (ypT1aV0N0Pn0R1).Conclusion: Renal percutaneous IRE appears to be a safe treatment for pT1a RCC but requires substantial procedural effort. Resection specimens of the ablation zone revealed a high rate of microscopic incomplete ablation 4 weeks after IRE. According to these initial study results, curative, kidney-sparing ablation of T1a RCC appears possible but needs technical improvement to ensure complete ablation. [ABSTRACT FROM AUTHOR]

Background: The cytokine system RANKL (receptor activator of NF-κB ligand), its receptor RANK and the antagonist OPG (osteoprotegerin) play a critical role in bone turnover. Our investigation was conducted to describe the gene expression at primary tumour site in prostate cancer patients and correlate the results with Gleason Score and PSA level.Methods: Seventy-one samples were obtained from prostate cancer patients at the time of radical prostatectomy and palliative prostate resection (n = 71). Patients with benign prostate hyperplasia served as controls (n = 60). We performed real-time RT-PCR after microdissection of the samples.Results: The mRNA expression of RANK was highest in tumour tissue from patients with bone metastases (p < 0.001) as compared to BPH or locally confined tumours, also shown in clinical subgroups distinguished by Gleason Score (< 7 or ≥ 7, p = 0.028) or PSA level (< 10 or ≥ 10 µg/l, p = 0.004). RANKL and OPG mRNA expression was higher in tumour tissue from patients with metastatic compared to local disease. The RANKL/OPG ratio was low in normal prostate tissue and high tumours with bone metastases (p < 0.05). Expression of all three cytokines was high in BPH tissue but did not exceed as much as in the tumour tissue.Conclusion: We demonstrated that RANK, RANKL and OPG are directly expressed by prostate cancer cells at the primary tumour site and showed a clear correlation with Gleason Score, serum PSA level and advanced disease. In BPH, mRNA expression is also detectable, but RANK expression does not exceed as much as compared to tumour tissue. [ABSTRACT FROM AUTHOR]

Introduction: If technically feasible, organ-preservation is indicated for T1 renal cell carcinoma (RCC), since partial nephrectomy (PN) is equivalent to radical nephrectomy with regard to tumor-specific survival and probably achieves better overall survival. Treatment results of a training clinic were assessed with regard to guideline adherence and treatment quality. Methods: Based on 220 open interventions in the time periods 2006-2009 (TP1) and 2010-2013 (TP2), a retrospective single center examination was performed to determine the influence of patient-age, sex, BMI, ASA-score, preoperative eGFR, PADUA-score and surgeon's experience on PN-rate and trifecta-outcome (R0 resection, warm ischemia time ≤25 min, no intraoperative complications and no blood-transfusion and postoperative complications grade ≤1 Clavien and Dindo). Results: PN-rate increased from 36.1 % in TP1 to 72.4 % in TP2. Despite significantly higher PADUA-scores in TP2 than in TP1 ( p = 0.0038), the trifecta-rate did not differ significantly (TP1 65.7 %; TP2 70.8 %; p = 0.666). Only the PADUA-score exerted an independent influence on the endpoints 'organ-preservation' and 'trifecta-outcome'. Conclusions: This study again demonstrated that the PADUA-score is a robust predictor of technical feasibility and treatment outcome for open PN. Consistent implementation of guidelines for nephron sparing surgery in RCC ≤7 cm is possible even in the setting of a training clinic and need not be associated with compromised treatment quality despite the increasing level of difficulty. Depending on the author, there are various definitions of trifecta-outcome. A uniform trifecta-concept would be desirable. [ABSTRACT FROM AUTHOR]

Purpose: Current systemic treatment of targeted therapies, namely the vascular endothelial growth factor-antibody (VEGF-AB), VEGF receptor tyrosine kinase inhibitor (TKI) and mammalian target of rapamycin (mTOR) inhibitors, have improved progression-free survival and replaced non-specific immunotherapy with cytokines in metastatic renal cell carcinoma (mRCC). Methods: A panel of experts convened to review currently available phase 3 data for mRCC treatment of approved agents, in addition to available EAU guideline data for a collaborative review as the plurality of substances offers different options of first-, second- and third-line treatment with potential sequencing. Results: Sunitinib and pazopanib are approved treatments in first-line therapy for patients with favorable- or intermediate-risk clear cell RCC (ccRCC). Temsirolimus has proven benefit over interferon-alfa (IFN-α) in patients with non-clear cell RCC (non-ccRCC). In the second-line treatment TKIs or mTOR inhibitors are treatment choices. Therapy options after TKI failure consist of everolimus and axitinib. Available third-line options consist of everolimus and sorafenib. Recently, nivolumab, a programmed death-1 (PD1) checkpoint inhibitor, improved overall survival benefit compared to everolimus after failure of one or two VEGFR-targeted therapies, which is likely to become the first established checkpoint inhibitor in mRCC. Data for the sequencing of agents remain limited. Conclusions: Despite the high level of evidence for first and second-line treatment in mRCC, data for third-line therapy are limited. Possible sequences include TKI-mTOR-TKI or TKI-TKI-mTOR with the upcoming checkpoint inhibitors in perspective, which might settle a new standard of care after previous TKI therapy. [ABSTRACT FROM AUTHOR]

Aim: This study was designed to assess the possible usefulness of shear-wave elastography in differentiating between benign and malignant tissue in prostate neoplasia. Patients and methods: A total of 120 prostate tissue samples were obtained from 10 patients treated by radical prostatectomy and investigated pre-operatively by ultrasound elastography followed by directed biopsy. After resection, whole-mount sectioning and histological examination was performed. The predictions based on shear-wave elastography were compared with biopsy and histological results. Results: The comparison between the results of shear-wave elastography and those of biopsy was performed by receiver operating characteristic analysis, which suggested an optimum cut-off tissue elasticity value of 50 kPa, in agreement with earlier studies aimed at distinguishing between benign and malignant tissue. However, the diagnostic selectivity (and thus the diagnostic power) was poor (area under the curve 0.527, which hardly differs from the value of 0.500 that would correspond to a complete lack of predictive power); furthermore, application of this cut-off value to the samples led to a sensitivity of only 74% and a specificity of only 43%. An analogous comparison between the results of shear-wave elastography and those of whole-mount histology, which itself is more reliable than biopsy, gave an even poorer diagnostic selectivity (sensitivity of 62%, specificity of 35%). Meaningful association with Gleason score was not found for D'Amico risk groups (p = 0.35). Conclusions: The (negative) findings of this investigation add to the dissonance among results of studies investigating the possible value of shear-wave elastography as a diagnostic tool to identify malignant neoplasia. There is a clear need for further research to elucidate the diversity of study results and to identify the usefulness, if any, of the method in question. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the present study was to compare long-term donor outcomes after open and laparoscopic living donor nephrectomy. The focus was on pregnancy rates, hypertension and quality of life parameters. Materials and Methods: Data were retrospectively collected using our institution's electronic database and a structured questionnaire. The study included 30 donors after open donor nephrectomy (ODN) and 131 donors after laparoscopic donor nephrectomy (LDN). Results: Demographic data did not differ between groups. When asked for their preference, significantly more donors in the LDN group would choose the same surgical approach again. The overall frequency of postoperative complications was significantly lower in the LDN group. The incidence of grade III complications was 2% after LDN and 10% after ODN (p = 0.79). Only 2 out of 15 female donors aged between 18 and 45 years delivered a healthy child after DN. On interview, only 4 out of 15 female donors declared the desire to have children after DN. Conclusions: From the donor perspective, long-term outcomes after LDN are more favorable than after ODN. To ensure favorable functional outcomes, strict preoperative donor selection and diligent long-term donor follow-up are required. [ABSTRACT FROM AUTHOR]

Introduction: Transurethral resection risks excessive absorption of irrigating fluid with potentially severe or lifethreatening consequences. We determined the amount of absorbed saline irrigation fluid during photoselective vaporisation of the prostate (PVP) and bipolar transurethral resection of the prostate (bTURP). Patients and Methods: Patients at our institution treated by one of these methods were monitored by the alcometric method: ethanol is added to the irrigation fluid and blood alcohol is measured with a breathalyser. Various possible correlations were investigated. Results: Data from 71 patients (36 PVP, 35 bTURP) were analysed. Detection of any absorption was more frequent under bTURP (71% of patients) than under PVP (39%; p = 0.006). Absorption in the volume range 500-1,000 ml was conspicuously more frequent in the bTURP procedure than in PVP. Conclusions: Presence of absorption was more frequent under bTURP than under PVP. However, high-volume absorption was more frequent during bTURP than in PVP. [ABSTRACT FROM AUTHOR]

Background: Irreversible electroporation (IRE) as newer ablation modality has been introduced and its clinical niche is under investigation. At present just one IRE system has been approved for clinical use and is currently commercially available (NanoKnife® system). In 2014, the International Working Group on Image-Guided Tumor Ablation updated the recommendation about standardization of terms and reporting criteria for image-guided tumor ablation. The IRE method is not covered in detail. But the non-thermal IRE method and the NanoKnife System differ fundamentally from established ablations techniques, especially thermal approaches, e.g. radio frequency ablation (RFA). Material/Methods: As numerous publications on IRE with varying terminology exist so far - with numbers continuously increasing - standardized terms and reporting criteria of IRE are needed urgently. The use of standardized terminology may then allow for a better inter-study comparison of the methodology applied as well as results achieved. Results: Thus, the main objective of this document is to supplement the updated recommendation for image-guided tumor ablation by outlining a standardized set of terminology for the IRE procedure with the NanoKnife Sytem as well as address essential clinical and technical informations that should be provided when reporting on IRE tumor ablation. Conclusions: We emphasize that the usage of all above recommended reporting criteria and terms can make IRE ablation reports comparable and provide treatment transparency to assess the current value of IRE and provide further development. [ABSTRACT FROM AUTHOR]

Objectives To report pre-specified and exploratory results on the effect of different surgical approaches on erectile function ( EF) after nerve-sparing radical prostatectomy (ns RP) obtained from the multicentre, randomised, double-blind, double-dummy REACTT trial of tadalafil (once a day [OaD] or on-demand [ pro-re-nata, PRN]) vs placebo. Patients and Methods Patients aged <68 years with normal preoperative EF who underwent nsRP for localised prostate cancer (Gleason ≤7, prostate-specific antigen [PSA] <10 ng/mL) were randomised after nsRP 1:1:1 to 9-month double-blind treatment with tadalafil 5 mg OaD, tadalafil 20 mg PRN, or placebo, followed by 6-week drug-free washout, and 3-month open-label OaD treatment (all patients). Recovery of EF was defined as an International Index of Erectile Function (IIEF)-EF domain score of ≥22 and normal orgasmic function was defined based on IIEF Question 10. Both parameters were analysed at the end of washout using logistic regression including terms for treatment, country, visit, visit-by-treatment interaction, age group, nerve-sparing score (perfect = 2, non-perfect >2), and surgical approach (open surgery, robot-assisted laparoscopy, conventional laparoscopy, other). Time to EF recovery was analysed post hoc with a Cox proportional-hazards model including terms for treatment, age-group, country, surgical approach and surgery-by-treatment interaction. Results Of 422 patients treated, 189 underwent open surgery, 115 robot-assisted laparoscopy, 88 conventional laparoscopy and 30 surgery classified as 'other'. The odds of achieving EF recovery at the end of drug-free washout were about twice as high for the robot-assisted laparoscopy group compared with the open surgery group (odds ratio 2.42; 95% confidence interval [ CI] 1.24, 4.72; P = 0.029). Patients who underwent robot-assisted laparoscopy were significantly more likely to recover during double-blind treatment compared with patients who underwent open surgery (hazard ratio 1.92; 95% CI 1.17, 3.15; P = 0.010). No favourable effect of conventional laparoscopy compared with open surgery could be seen. Conclusion These results may provide further insights into the role of surgery on EF recovery after ns RP. However, the trial was not designed for these analyses and further prospective studies are needed. [ABSTRACT FROM AUTHOR]

Background: Docetaxel plus prednisone is a standard treatment for castration-resistant prostate cancer. Cyclophosphamide may be an effective combination partner. Methods: This randomised, multicentre, phase II trial compared the combination therapy of docetaxel plus prednisone plus cyclophosphamide with the standard therapy of docetaxel plus prednisone. Results: Thirty-three patients received six 3-week treatment cycles (in total 171 cycles). During treatment, an adequate decline in prostate-specific antigen was seen in both groups (p = 0.068) without between-group differences (p = 0.683). No relevant differences between within-group changes were observed for blood pressure, weight, pain score, laboratory variables or quality of life. There were no serious side effects apart from leucopenia requiring treatment (docetaxel + prednisone + cyclophosphamide arm) and no drug-related withdrawals; all three fatalities were considered to be cancer related. Conclusions: The oncological effectiveness and tolerability of docetaxel plus prednisone were supported; an additional effect of cyclophosphamide was not detected. However, the small number of patients and short observation period restrict the generalisability of the results. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction: Radical retropubic prostatectomy (RRP) is associated with an increased risk of intraoperative blood loss and the necessity of transfusions. This prospective randomised clinical study evaluates the influence of thoracic epidural analgesia (TEA) on blood loss in RRP. Materials and Methods: 235 patients were randomised: TEA in group 1 (n = 116; general anaesthesia + TEA) comprised continuous administration of 0.25% bupivacaine, while group 2 (n = 119; general anaesthesia alone) received intravenous analgesia with fentanyl (intubation: 2 µg/kg; maintenance: 0.1- 0.3 mg). A restrictive infusion regimen (<1,000 ml until specimen removal) was administered in both groups. Blood loss, infusion rates and anaesthesiological parameters were recorded and analysed using regression models and analyses of variance. Results: Haemoglobin difference between the pre- and the first postoperative day (group 1: 3.35 ± 1.16 g/dl; group 2: 3.56 ± 1.42 g/dl; p = 0.19), overall blood loss (group 1: 665 ± 431.5 ml; group 2: 705 ± 881 ml; p = 0.73) and transfusion rates (0.4% intraoperatively; 2.55% postoperatively; p = 1.0) did not show group differences. In regression analysis blood loss was influenced by preoperative haemoglobin levels (p < 0.0001), patients' weight (p = 0.018) and duration of the operation (p = 0.017). Conclusions: This study did not demonstrate a direct impact of TEA on intraoperative blood loss and transfusion rates in RRP. Further randomised clinical trials are needed to evaluate an impact of the different anaesthetic procedures presented alone or in combination on blood loss. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: Metabolic adaptations, such as increases in glucose and energy metabolism, play a pivotal role in the biology of RCC. PDK-1 and DJ-1/PARK7 are thought to control metabolic pathways in cancer. We investigated the expression of PDK-1 and DJ-1/PARK7 in RCC and their prognostic relevance. Methods: RCC tumor tissue and corresponding normal parenchyma samples were obtained from 91 patients with clear cell RCC. Expression of PDK-1 and DJ-1/PARK7 was determined on the mRNA and protein levels using quantitative RT-PCR and immunohistochemistry. Expression ratios tumor/normal were analyzed for associations with pathological stage and grade (Kruskal-Wallis ANOVA, chi-square test). Potential associations with progression-free and overall survival were analyzed using Cox regression models. Results: PDK-1 mRNA expression was up-regulated as compared to normal tissue ( p < 0.001). Differences were observed by tumor stage ( p < 0.05) with a trend toward lower expression with increasing stage ( p > 0.01). Expression ratio tumor/normal also showed differences by tumor stage with the lowest ratio observed in advanced (pT3) disease. MRNA expression data were confirmed on the protein level with the lowest protein expression in pT3 tumors. PDK-1 expression ratio tumor/normal was inversely associated with outcome after adjustment for stage and grade (HR, 0.54; 95 % CI, 0.31-0.94). No associations observed for DJ-1/PARK7 expression. Conclusions: PDK is up-regulated in RCC, but down-regulation may be associated with progression toward a metastasizing behavior. Given the role of PDK-1 in the control of glucose metabolism, aerobic glycolysis via up-regulation of PDK-1 may be an early event in RCC development, but less relevant for the progression toward an aggressive phenotype. [ABSTRACT FROM AUTHOR]

Background: Patients with prostate cancer face the difficult decision between a wide range of therapeutic options. These men require elaborate information about their individual risk profile and the therapeutic strategies´ risks and benefits to choose the best possible option. In order to detect time trends and quality improvements between an early patient population (2003/2004) and a later reference group (2007/2008) data was analysed with regards to epidemiologic parameters, differences in diagnostics and the type and ranking of the recommended therapies taking into account changes to Gleason Grading System and implementation of new therapeutic strategies, particularly Active surveillance, in 2005.Methods: Data from all 496 consecutive patients who received consultation in 2003/2004 (n = 280) and 2007/2008 (n = 216) was retrospectively evaluated. Categorical variables were compared using the Chi-square test. Dependent variables were analysed using the unpaired Students´ t-test and the Mann-Whitney U-test.Results: The cohorts were comparable concerning clinical stage, initial PSA, prostate volume, comorbidities and organ confined disease. Patients in Cohort I were younger (66.44 vs. 69.31y; p < .001) and had a longer life expectancy (17.22 vs. 14.75y; p < .001). 50.9%, 28.2% and 20.9% in Cohort I and 37.2%, 39.6% and 23.2% in Cohort II showed low-, intermediate- and high-risk disease (D´Amico) with a trend towards an increased risk profile in Cohort II (p = .066). The risk-adapted therapy recommended as first option was radical prostatectomy for 91.5% in Cohort I and 69.7% in Cohort II, radiation therapy for 83.7% in Cohort I and 50.7% in Cohort II, and other therapies (brachytherapy, Active surveillance, Watchful waiting, high-intensity focused ultrasound) for 6.5% in Cohort I and 6.9% in Cohort II (p < .001). Radiation therapy was predominant in both cohorts as second treatment option (p < .001). Time trends showing quality improvement involved an increase in biopsy cores (9.95 ± 2.38 vs. 8.43 ± 2.29; p < .001) and an increased recommendation for bilateral nerve sparing (p < .001).Conclusion: In the earlier years, younger patients with a more favourable risk profile presented for interdisciplinary consultation. A unilateral recommendation for radical prostatectomy and radiation therapy was predominant. In the later years, the patient population was considerably older. However, this group may have benefitted from optimised diagnostic possibilities and a wider range of treatment options. [ABSTRACT FROM AUTHOR]

Objective: The risk of local recurrence after radical prostatectomy (RP) is considerably dependent on local tumor stage. To improve local staging, the aim of this study was to assess the feasibility of quantitative methylation-specific PCR (Q-MSP) for the identification of promoter hypermethylation of the detoxifying glutathione-S-transferase P1 gene (GSTP1) to detect occult prostate cancer (PCa) cells in the prostatic fossa after RP. Methods: A total of 39 consecutive patients with clinically organ-confined PCa underwent RP. After gland excision, biopsies were obtained from eight defined areas of the prostatic fossa and bisected for both histopathological and molecular analyses. Results were related to clinicopathological data including tumor stage, Gleason score, prostate-specific antigen (PSA), and biochemical recurrence. Results: Of 39 patients, 11 with PCa had at least one positive molecular margin status indicated by GSTP1 methylation. These included 5 of 17 (29.4%) with organ-confined and 6 of 22 (27.3%) with advanced (≥pT3 and/or pN+) PCa. GSTP1 methylation in surgical margins strongly correlated with histopathological R-status ( P = 0.022) and preoperative PSA ( P = 0.01) whereas no association with tumor stage (pT2 vs pT3), grade (Gleason score <7 vs ≥7), and lymph node status was found. No patient experienced biochemical relapse. Conclusions: GSTP1 hypermethylation detected by Q-MSP in prostatic fossa biopsies after RP is well suited for the detection of occult tumor cells in surgical margins. However, the limited number of patients and the short-term follow-up does not allow definite conclusions on the prognostic value of GSTP1 in surgical margins. [ABSTRACT FROM AUTHOR]

Objective. To evaluate and compare noncontinent and continent urinary diversion after radical cystectomy in patients with bladder cancer. Methods. A total of 301 patients submitted to radical cystectomy at the Charit'e-University Hospital Berlin from 1993 to 2007 including 146 with an ileal conduit and 115 with an ileal neobladder. Clinical and pathological data as well as oncological outcome were retrospectively analyzed and compared. Quality of life was analyzed using the EORTC QLQ-C30 and BLM30 questionnaires. Results. 69.1% and 69.6% of all patients who received an ileal conduit and ileal neobladder, respectively, developed early complications. The two groups differed significantly concerning the occurrence of postoperative ileus (P = 0.02) favoring patients who received an ileal conduit but not with regard to any other early-onset complication evaluated. Patients with ileal neobladder had a significantly better global health status and quality of life (P = 0.02), better physical functioning (P = 0.02), but also a higher rate of diarrhoea (P = 0.004). Conclusion. Cystectomy with any type of diversion remains a complication-prone surgery. Even if the patient groups are not homogeneous in all respects, there are many arguments in favor of the ileal neobladder as the urinary diversion of choice. [ABSTRACT FROM AUTHOR]

Objective. To evaluate and compare noncontinent and continent urinary diversion after radical cystectomy in patients with bladder cancer. Methods. A total of 301 patients submitted to radical cystectomy at the Charit'e-University Hospital Berlin from 1993 to 2007 including 146 with an ileal conduit and 115 with an ileal neobladder. Clinical and pathological data as well as oncological outcome were retrospectively analyzed and compared. Quality of life was analyzed using the EORTC QLQ-C30 and BLM30 questionnaires. Results. 69.1% and 69.6% of all patients who received an ileal conduit and ileal neobladder, respectively, developed early complications. The two groups differed significantly concerning the occurrence of postoperative ileus (P = 0.02) favoring patients who received an ileal conduit but not with regard to any other early-onset complication evaluated. Patients with ileal neobladder had a significantly better global health status and quality of life (P = 0.02), better physical functioning (P = 0.02), but also a higher rate of diarrhoea (P = 0.004). Conclusion. Cystectomy with any type of diversion remains a complication-prone surgery. Even if the patient groups are not homogeneous in all respects, there are many arguments in favor of the ileal neobladder as the urinary diversion of choice. [ABSTRACT FROM AUTHOR]

Purpose: Salvage radiotherapy (SRT) is commonly used to treat patients with biochemical failure after radical prostatectomy (RP). Retrospective series have demonstrated biochemical response in approximately 60–75% of patients, but only a significantly lower rate of patients achieves a response with a decrease of the prostate-specific antigen (PSA) to a value below the limits of detectability. Therefore, long-term response at 10 years is only about 20–25% in all of these patients. The purpose of this study was to determine prognostic factors with impact on achieving the undetectable PSA range after SRT and to define the role of this end point. Methods and Materials: Between 1997 and 2004, 162 patients received SRT at the Charité Universitätsmedizin, Berlin. No patient had hormonal treatment before SRT and 90% of the patients (143) had a SRT dose of 66 Gy. We analyzed the impact of nine potential risk factors on achieving an undetectable PSA after RT and on biochemical relapse–free survival (bNED) after SRT. Results: Median follow-up time was 41.5 months and median PSA pre-RT was 0.33 ng/mL. Calculated bNED for 3.5 years was 54%. A total of 60% of the patients achieved an undetectable PSA after SRT. Univariate analysis demonstrated statistically significant predictors of biochemical progression after SRT: Gleason score (p = 0.01), PSA pre-SRT (p = 0.031), tumor stage (p = 0.047), and persistent detectable PSA after RT (p < 0.00005). In multivariate analysis, margin status (p = 0.017) and PSA pre-SRT (p = 0.002) were significant predictors of an undetectable PSA after SRT. The most significant independent predictor of bNED was “PSA undetectable after RT” (p < 0.0005) with a hazard ratio of 8.4, thus leading to a calculated bNED at 3.5 years of 75% compared with only 18% for those patients, who did not achieve an undetectable PSA after SRT. The rate of severe Grade 3-4 side effects was below 2.5%. Conclusions: The study represents one of the largest retrospective single-institution series of SRT for increasing PSA after RP in patients without any hormonal treatment before the initiation of SRT. Our findings suggest that achieving an undetectable PSA after RT is an important prognosticator for a high chance of cure and patients with a low PSA pre-SRT, positive surgical margins, and low tumor stage at the time of RP are best candidates for SRT. [Copyright &y& Elsevier]