Magnetic resonance imaging-guided transurethral ultrasound ablation of prostate tissue in patients with localized prostate cancer: single-center evaluation of 6-month treatment safety and functional outcomes of intensified treatment parameters.

OBJECTIVES: To evaluate the effect of intensified treatment parameters on safety, functional outcomes, and PSA after MR-Guided Transurethral Ultrasound Ablation (TULSA) of prostatic tissue. PATIENTS AND METHODS: Baseline and 6-month follow-up data were collected for a single-center cohort of the multicenter Phase I (n = 14/30 at 3 sites) and Pivotal (n = 15/115 at 13 sites) trials of TULSA in men with localized prostate cancer. The Pivotal study used intensified treatment parameters (increased temperature and spatial extent of ablation coverage). The reporting site recruited the most patients to both trials, minimizing the influence of physician experience on this comparison of adverse events, urinary symptoms, continence, and erectile function between subgroups of both studies. RESULTS: For Phase I and TACT patients, median age was 71.0 and 67.0 years, prostate volume 41.0 and 44.5 ml, and PSA 6.7 and 6.7 ng/ml, respectively. All 14 Phase I patients had low-risk prostate cancer, whereas 7 of 15 TACT patients had intermediate-risk disease. Baseline IIEF, IPSS, quality of life, and pad use were similar between groups. Pad use at 1 month and quality of life at 3 months favored Phase I patients. At 6 months, there were no significant differences in functional outcomes or adverse events. CONCLUSION: TULSA demonstrated acceptable clinical safety in Phase I trial. Intensified treatment parameters in the TACT Pivotal trial increased ablation coverage from 90 to 98% of the prostate without affecting 6-month adverse events or functional outcomes. Long-term follow-up and 12-month biopsies are needed to evaluate oncological safety.

Adherence to the EAU guideline recommendations for systemic chemotherapy in penile cancer: results of the E-PROPS study group survey.

OBJECTIVES: To validate the adherence of urologists to chemotherapy recommendations given in the EAU guidelines on PeCa. The European Association of Urology (EAU) guidelines on penile cancer (PeCa) are predominantly based on retrospective studies with low level of evidence. MATERIALS AND METHODS: A 14-item-survey addressing general issues of PeCa treatment was developed and sent to 45 European hospitals. 557 urologists participated in the survey of which 43.5%, 19.3%, and 37.2% were in-training, certified, and in leading positions, respectively. Median response rate among participating departments was 85.7% (IQR 75-94%). Three of 14 questions addressed clinical decisions on neoadjuvant, adjuvant, and palliative chemotherapy. Survey results were analyzed by bootstrap-adjusted multivariate logistic-regression-analysis to identify predictors for chemotherapy recommendations consistent with the guidelines. RESULTS: Neoadjuvant, adjuvant, and palliative chemotherapy was recommended according to EAU guidelines in 21%, 26%, and 48%, respectively. For neoadjuvant chemotherapy, urologists holding leading positions or performing chemotherapy were more likely to recommend guideline-consistent treatment (OR 1.85 and 1.92 with p(bootstrap) = 0.007 and 0.003, respectively). Supporting resources (i.e., guidelines, textbooks) were used by 23% of survey participants and significantly improved consistency between treatment recommendations and Guideline recommendations in all chemotherapy settings (p(bootstrap) = 0.010-0.001). Department size and university center status were no significant predictors for all three endpoints. CONCLUSIONS: In this study, we found a very low rate of adherence to the EAU guidelines on systemic treatment for PeCa. Further investigations are needed to clarify whether this missing adherence is a consequence of limited individual knowledge level or of the low grade of guideline recommendations.

Twelve-month prostate volume reduction after MRI-guided transurethral ultrasound ablation of the prostate.

PURPOSE: To quantitatively assess 12-month prostate volume (PV) reduction based on T2-weighted MRI and immediate post-treatment contrast-enhanced MRI non-perfused volume (NPV), and to compare measurements with predictions of acute and delayed ablation volumes based on MR-thermometry (MR-t), in a central radiology review of the Phase I clinical trial of MRI-guided transurethral ultrasound ablation (TULSA) in patients with localized prostate cancer. MATERIALS AND METHODS: Treatment day MRI and 12-month follow-up MRI and biopsy were available for central radiology review in 29 of 30 patients from the published institutional review board-approved, prospective, multi-centre, single-arm Phase I clinical trial of TULSA. Viable PV at 12 months was measured as the remaining PV on T2-weighted MRI, less 12-month NPV, scaled by the fraction of fibrosis in 12-month biopsy cores. Reduction of viable PV was compared to predictions based on the fraction of the prostate covered by the MR-t derived acute thermal ablation volume (ATAV, 55°C isotherm), delayed thermal ablation volume (DTAV, 240 cumulative equivalent minutes at 43°C thermal dose isocontour) and treatment-day NPV. We also report linear and volumetric comparisons between metrics. RESULTS: After TULSA, the median 12-month reduction in viable PV was 88%. DTAV predicted a reduction of 90%. Treatment day NPV predicted only 53% volume reduction, and underestimated ATAV and DTAV by 36% and 51%. CONCLUSION: Quantitative volumetry of the TULSA phase I MR and biopsy data identifies DTAV (240 CEM43 thermal dose boundary) as a useful predictor of viable prostate tissue reduction at 12 months. Immediate post-treatment NPV underestimates tissue ablation. KEY POINTS: • MRI-guided transurethral ultrasound ablation (TULSA) achieved an 88% reduction of viable prostate tissue volume at 12 months, in excellent agreement with expectation from thermal dose calculations. • Non-perfused volume on immediate post-treatment contrast-enhanced MRI represents only 64% of the acute thermal ablation volume (ATAV), and reports only 60% (53% instead of 88% achieved) of the reduction in viable prostate tissue volume at 12 months. • MR-thermometry-based predictions of 12-month prostate volume reduction based on 240 cumulative equivalent minute thermal dose volume are in excellent agreement with reduction in viable prostate tissue volume measured on pre- and 12-month post-treatment T2w-MRI.

Incidental appendectomy during robotic laparoscopic prostatectomy-safe and worth to perform?

PURPOSE: The purpose of this study is to investigate the safety and patients' benefit of incidental appendectomy during robot-assisted laparoscopic radical prostatectomy (RALRP). METHODS: Fifty-three patients, who had incidental appendectomy during RALRP between January 2012 and March 2014, were enrolled to this study. To evaluate the safety of the procedure, following parameters were evaluated: patient age, duration of surgery, perioperative complications (classified by Clavien-Dindo), time to bowel movement, and length of hospital stay. Furthermore, intraoperative visual appearance, location, and histopathological evaluation of the appendix were evaluated. Data was analyzed by descriptive statistics. RESULTS: Mean age of patients was 61 years, the average hospital stay 5 days. No perioperative complications occurred. The appendix was unsuspicious in 39 patients (73.6%); 14 patients (26.4%) had macroscopically signs of inflammation. Of the 53 resected appendixes, the histopathological evaluation showed 33 (62.2%) inconspicuous appendices, 11 (20.8%) post-inflammatory changes, 4 (7.5%) with chronical signs of inflammation and 3 (5.7%) with signs of acute inflammation. In 2 patients (3.8%), low-grade mucinous neoplasms were found in the specimens. CONCLUSIONS: Incidental appendectomy during RALRP is a feasible procedure. With regard to inflammation and neoplastic changes, incidental appendectomy can be considered for patients scheduled for robot-assisted prostate surgery.

Prognostic significance of Fuhrman grade and age for cancer-specific and overall survival in patients with papillary renal cell carcinoma: results of an international multi-institutional study on 2189 patients.

PURPOSE: Because the prognostic impact of the clinical and pathological features on cancer-specific survival (CSS) and overall survival (OS) in patients with papillary renal cell carcinoma (papRCC) is still controversial, we want to assess the impact of clinicopathological features, including Fuhrman grade and age, on survival in surgically treated papRCC patients in a large multi-institutional series. METHODS: We established a comprehensive multi-institutional database of surgically treated papRCC patients. Histopathological data collected from 2189 patients with papRCC after radical nephrectomy or nephron-sparing surgery were pooled from 18 centres in Europe and North America. OS and CSS probabilities were estimated using the Kaplan-Meier method. Multivariable competing risks analyses were used to assess the impact of Fuhrman grade (FG1-FG4) and age groups (<50 years, 50-75 years, >75 years) on cancer-specific mortality (CSM). RESULTS: CSS and OS rates for patients were 89 and 81% at 3 years, 86 and 75% at 5 years and 78 and 41% at 10 years after surgery, respectively. CSM differed significantly between FG 3 (hazard ratio [HR] 4.22, 95% confidence interval [CI] 2.17-8.22; p < 0.001) and FG 4 (HR 8.93, 95% CI 4.25-18.79; p < 0.001) in comparison to FG 1. CSM was significantly worse in patients aged >75 (HR 2.85, 95% CI 2.06-3.95; p < 0.001) compared to <50 years. CONCLUSIONS: FG is a strong prognostic factor for CSS in papRCC patients. In addition, patients older than 75 have worse CSM than patients younger than 50 years. These findings should be considered for clinical decision making.

Quality of life and functional outcome after infravesical desobstruction and HIFU treatment for localized prostate cancer.

BACKGROUND: To evaluate quality of life, functional and oncological outcome after infravesical desobstruction and HIFU treatment for localized prostate cancer. METHODS: One hundred thirty-one patients, treated with TURP and HIFU in a single institution were followed up for oncological and functional outcome. Oncological outcome was quantified by biochemical recurrence free survival using the Stuttgart and Phoenix criteria. Quality of life was assessed by usage of standardized QLQ-C30 and QLQ-PR25 questionnaires. In addition, functional questionnaires such as IPSS and IIEF-5 were used. Complications were assessed by the Clavien-Dindo classification. RESULTS: One hundred thirty-one patients with a mean age of 72.8 years (SD: 6.0) underwent HIFU for prostate cancer (29.0% low risk, 58.8% intermediate risk, 12.2% high risk). PSA nadir was 0.6 ng/ml (SD: 1.2) after a mean of 4.6 months (SD: 5.7). Biochemical recurrence free survival defined by Stuttgart criteria was 73.7%, 84.4% and 62.5% for low-, intermediate- and high-risk patients after 22.2 months. Complications were grouped according to Clavien-Dindo and occurred in 10.7% (grade II) and 11.5% (grade IIIa) of cases. 35.1% of patients needed further treatment for bladder neck stricture. Regarding incontinence, 14.3%, 2.9% and 0% of patients had de novo urinary incontinence grade I°, II° and III° and 3.8% urge incontinence due to HIFU treatment. Patients were asked for the ability to have intercourse: 15.8%, 58.6% and 66.7% of patients after non-, onesided and bothsided nervesparing procedure were able to obtain sufficient erection for intercourse, respectively. Regarding quality of life, mean global health score according to QLQ-C30 was 69.4%. CONCLUSION: HIFU treatment for localized prostate cancer shows acceptable oncological safety. Quality of life after HIFU is better than in the general population and ranges within those of standard treatment options compared to literature. HIFU seems a safe valuable treatment alternative for patients not suitable for standard treatment.

Predictive factors for immediate continence after radical prostatectomy.

PURPOSE: To identify predictive factors for immediate continence after radical prostatectomy. PATIENTS AND METHODS: A total of 1553 patients underwent radical prostatectomy in a single institution (670 RRP, 883 RARP), had complete perioperative data and follow-up for urinary continence and were included in this prospective analysis. Immediate continence was defined as no pad usage after catheter removal. Evaluated parameters included age, body mass index, ECOG performance status, erectile function, prostate volume, PSA, Gleason score, tumor stage and D'Amico risk groups, as well as surgical approach (RRP, RARP), surgeon volume, nerve-sparing, lymphadenectomy, blood transfusions and duration of catheterization. RESULTS: A total of 240 men (15.5 %) did not require any pads 1 day or later after removal of the transurethral catheter. Correlation of parameters with immediate continence revealed significance for age (p < 0.001), ECOG-score (p = 0.025), erectile function (p = 0.001), nerve-sparing (p = 0.022), Gleason score (p = 0.002) and surgeon volume (p ≤ 0.022). Multivariate analyses identified IIEF-score >21 (p = 0.031), ECOG (p < 0.05), bilateral nerve-sparing (p = 0.049), Gleason score <3 + 4 (p ≤ 0.028), less blood transfusion (p ≤ 0.044) and surgeon volume (p ≤ 0.042) as the remaining prognostic parameters for immediate continence after radical prostatectomy. The type of surgical approach (robotic vs. open radical prostatectomy) did not yield significant influence. CONCLUSION: Evaluating continence in a contemporary prospective cohort revealed 15.5 % of patients never requiring a pad postoperatively. Predictive parameters for immediate continence were erectile function, ECOG, bilateral nerve-sparing, less blood transfusion and Gleason score. Furthermore, the surgeon's experience but not his operative technique had a significant impact on immediate postoperative continence.

Follow-up after focal therapy in renal masses: an international multidisciplinary Delphi consensus project.

PURPOSE: To establish consensus on follow-up (FU) after focal therapy (FT) in renal masses. To formulate recommendations to aid in clinical practice and research. METHODS: Key topics and questions for consensus were identified from a systematic literature research. A Web-based questionnaire was distributed among participants selected based on their contribution to the literature and/or known expertise. Three rounds according to the Delphi method were performed online. Final discussion was conducted during the "8th International Symposium on Focal Therapy and Imaging in Prostate and Kidney Cancer" among an international multidisciplinary expert panel. RESULTS: Sixty-two participants completed all three rounds of the online questionnaire. The panel recommended a minimum follow-up of 5 years, preferably extended to 10 years. The first FU was recommended at 3 months, with at least two imaging studies in the first year. Imaging was recommended biannually during the second year and annually thereafter. The panel recommended FU by means of CT scan with slice thickness ≤3 mm (at least three phases with excretory phase if suspicion of collecting system involvement) or mpMRI. Annual checkup for pulmonary metastasis by CT thorax was advised. Outside study protocols, biopsy during follow-up should only be performed in case of suspicion of residual/persistent disease or radiological recurrence. CONCLUSIONS: The consensus led to clear FU recommendations after FT of renal masses supported by a multidisciplinary expert panel. In spite of the low level of evidence, these recommendations can guide clinicians and create uniformity in the follow-up practice and for clinical research purposes.

Collecting system invasion and Fuhrman grade but not tumor size facilitate prognostic stratification of patients with pT2 renal cell carcinoma.

PURPOSE: The 7th edition of TNM for renal cell carcinoma introduced a subdivision of pT2 tumors at a 10 cm cutoff. In the present multicenter study the influence of tumor size as well as further clinical and histopathological parameters on cancer specific survival in patients with pT2 tumors was evaluated. MATERIALS AND METHODS: A total of 670 consecutive patients with pT2 tumors (10.4%) of 6,442 surgically treated patients with all tumor stages were pooled (mean followup 71.4 months). Tumors were reclassified according to the current TNM classification, and subdivided in stages pT2a and pT2b. Cancer specific survival was analyzed using the Kaplan-Meier method, and univariable and multivariable analyses were used to assess the influence of several parameters on survival. RESULTS: Tumor size continuously applied and subdivided at 10 cm or alternative cutoffs did not significantly influence cancer specific survival. In addition to N/M stage, Fuhrman grade and collecting system invasion also had an independent influence on survival. Integration of a dichotomous variable subsuming Fuhrman grade and collecting system invasion (grade 3/4 and/or collecting system invasion present vs grade 1/2 and collecting system invasion absent) into multivariate models including established prognostic parameters resulted in improvement of predictive abilities by 11% (HR 2.3, p <0.001) for all pT2 cases and 151% (HR 3.1, p <0.001) for stage pT2N0M0 cases. CONCLUSIONS: Tumor size did not have a significant influence on cancer specific survival in pT2 tumors, neither continuously applied nor based on various cutoff values. To enhance prognostic discrimination, multifactorial staging systems including pathological features should be implemented. The prognostic relevance of the variable subsuming Fuhrman grade and collecting system invasion should be considered for future evaluation.

[Ureteric and testicular mestastasis 25 years after nephrectomy : Long-term survival with metastatic renal cell carcinoma]. / Harnleiter- und Hodenmetastase 25 Jahre nach Nephrektomie : Langjähriges Überleben mit einem metastasierten Nierenzellkarzinom.

A 70-year-old man with multiple metastasized renal cell carcinoma (RCC) presented himself in our clinic 25 years after initial diagnosis with newly developed hematuria and conspicuous right testis. The biopsy of the left ureter taken by ureterorenoscopy and the right orchiectomy show metastases of a clear cell RCC. This special case shows rare metastases in different organ systems. The individualized multimodal treatment led to a long-term survival with this metastasized disease. The presented case shows that late recurrences of RCC can occur years after initial diagnosis and should be considered at any time.

[Kidney injuries]. / Nierentrauma.

Most renal injuries in industrialized countries are caused by blunt trauma to the kidney. The management of renal trauma has always been and will always be controversial. Conservative management and aggressive intervention both have their proponents, but conservative treatment is generally favored nowadays, even in the case of grade IV/(V) trauma. Urinary diversion by nephrostomy tube or ureteral stenting is not mandatory in most cases because the extravasation resolves in up to 90% of cases. Overall, there is a tendency toward a multimodal approach in which the interventional radiologist is more and more often part of the team that takes care of the patient with high-grade injuries. The success rate of angioembolization is 70-80%. Long-term consequences can be hypertension or diminished kidney function.

Manifestation of congenital urethral diverticula in a 57-year-old male.

Congenital urethral diverticula are a rare finding in adult males. Most cases are diagnosed in childhood or adolescence because of voiding symptoms such as urinary dribbling. Diagnostic workup should include radiography and urethroscopy. The standard therapeutic approach is open surgical excision or endoscopic marsupialization. An unusual case of male congenital urethral diverticula that remained asymptomatic until age 57 is presented.

[Kidney trauma]. / Nierentrauma.

Most renal injuries in industrialized countries are caused by blunt trauma to the kidney. The management of renal trauma has always been and will always be controversial. Conservative management and aggressive intervention both have their proponents, but conservative treatment is generally favored nowadays, even in the case of grade IV/(V) trauma. Urinary diversion by nephrostomy tube or ureteral stenting is not mandatory in most cases because the extravasation resolves in up to 90% of cases. Overall, there is a tendency toward a multimodal approach in which the interventional radiologist is more and more often part of the team that takes care of the patient with high-grade injuries. The success rate of angioembolization is 70-80%. Long-term consequences can be hypertension or diminished kidney function.

[Elective organ-sparing surgery for renal tumors in patients with a normal contralateral kidney: long-term results]. / Elektive organerhaltende Nierentumorchirurgie bei normaler Gegenniere : Langzeitergebnisse.

Continuous improvements in radiological imaging techniques have enabled an earlier diagnosis of incidental renal tumors. The share of small renal tumors (4 cm can also be treated with nephron-sparing surgery. We report in this article our long-term oncological results of nephron-sparing surgery in patients with an elective indication.

[Imperative nephron-sparing surgery for cases of solitary kidney/bilateral tumors: long-term results]. / Imperative organerhaltende Nierentumorchirugie bei Einzelniere bzw. bilateralen Tumoren : Langzeitergebnisse.

Renal cell carcinoma is the most lethal amongst urological malignancies. Only surgical excision of the tumor offers the chance of curative therapy for patients with localized disease. Nephron-sparing surgery is mandatory for patients with renal tumors in both kidneys or in a solitary kidney in order to preserve renal function (imperative indication). Evaluation of patients with renal tumors in both kidneys or in a solitary kidney must weigh the surgical and oncological risks of nephron-sparing surgery against the morbidity of radical nephrectomy followed by hemodialysis and possibly renal transplantation. Herein we report our oncological and functional long-term results of nephron-sparing surgery in patients with an imperative indication and review the literature.

[Recurrence-free survival after radical prostatectomy and PDE-5 inhibitor intake]. / Rezidivfreies Überleben nach radikaler Prostatektomie und PDE-5-Hemmer-Einnahme.

BACKGROUND: Phosphodiesterase type 5 (PDE-5) inhibitors are widely used for penile rehabilitation and treatment of erectile dysfunction after radical prostatectomy. Recently, Michl et al. showed in a monocentric, retrospective and non-randomized analysis that PDE-5 inhibitors may cause higher biochemical recurrence rates after radical prostatectomy. This unexpected and serious adverse side effect of PDE-5 inhibitors was scrutinized on the basis of patients in our prospective tumor database. MATERIALS AND METHODS: We included 358 patients after radical prostatectomy with bilateral nerve-sparing and without neo- or adjuvant therapy during 2004 and 2015. In all, 65.9% of the patients regularly took PDE-5 inhibitors postoperatively, 34.1% did not. Patients with sporadic use were excluded from the primary analysis. We used Kaplan-Mayer analysis to compare biochemical recurrence rates in both groups (endpoint: PSA > 0.2 ng/ml or salvage therapy). RESULTS: Both groups showed comparable clinical parameters. There was no significant difference in recurrence-free survival (p = 0.9334): 60 months postoperatively 90.4% of men with PDE-5 intake vs. 90.8% of men without intake of PDE-5 inhibitors were recurrence-free. CONCLUSION: Although our analysis was constructed similar to the analysis of Michl et al., we could not confirm their results. Taken together with recent cohort study from Scandinavia, postoperative prescription of PDE-5 inhibitors seems to be safe and should be discussed with patients.

A prospective randomized controlled trial for assessment of perineal hydrodissection technique for nervesparing robot assisted radical prostatectomy.

BACKGROUND: This study prospectively evaluated the safety and efficacy of perineal hydrodissection in robot assisted nervesparing prostatectomy. METHODS: Patients were randomized for perineal, ultrasound guided hydrodissection (HD) before radical prostatectomy and compared with standard treatment (ST). Follow-up was done every 3 months, including erectile function (IIEF5-score), reported grade of erection, ability for sexual intercourse, continence, PSA. RESULTS: 21 patients were enrolled to this prospective study, 10 for ST and 11 for HD. No significant differences in demographic and preoperative oncological data between both groups were identified. Blood loss and time for surgery did not differ significantly. HD resulted in 66% (4/6) rate of positive surgical margins (PSM) in pT3 tumors vs 50% in ST (1/2; P = 0.67). Follow-up revealed higher IIEF scores, better ability for sexual intercourse and early continence in HD. CONCLUSIONS: Erectile function after radical prostatectomy was improved by perineal hydrodissection in this proof of principal study. However, careful patient selection and further studies are needed as perineal hydrodissection could result in increased positive surgical margins in pT3a tumors.

[Urethroplasty and simultaneous perineal prostatectomy after traumatic urethral disruption and carcinoma of the prostate]. / Harnröhrenplastik nach Urethraabriss und simultane perineale Prostatektomie.

We present a case of post-traumatic posterior urethral stricture and localized prostate cancer, which could be treated successfully with simultaneous radical perineal prostatectomy and membranous urethral stricture excision. After 6 months follow-up, the patient is continent with no evidence of stricture recurrence. Post-traumatic posterior urethral strictures can be managed surgically through a perineal approach with high success rates. Prostate surgery after pelvic fracture with posterior urethral distraction defects does not necessarily lead to stress urinary incontinence.

Further reduction of disqualification rates by additional MRI-targeted biopsy with transperineal saturation biopsy compared with standard 12-core systematic biopsies for the selection of prostate cancer patients for active surveillance.

BACKGROUND: Active surveillance (AS) is commonly based on standard 10-12-core prostate biopsies, which misclassify ~50% of cases compared with radical prostatectomy. We assessed the value of multiparametric magnetic resonance imaging (mpMRI)-targeted transperineal fusion-biopsies in men under AS. METHODS: In all, 149 low-risk prostate cancer (PC) patients were included in AS between 2010 and 2015. Forty-five patients were initially diagnosed by combined 24-core systematic transperineal saturation biopsy (SB) and MRI/transurethral ultrasound (TRUS)-fusion targeted lesion biopsy (TB). A total of 104 patients first underwent 12-core TRUS-biopsy. All patients were followed-up by combined SB and TB for restratification after 1 and 2 years. All mpMRI examinations were analyzed using PIRADS. AS was performed according to PRIAS-criteria and a NIH-nomogram for AS-disqualification was investigated. AS-disqualification rates for men initially diagnosed by standard or fusion biopsy were compared using Kaplan-Meier estimates and log-rank tests. Differences in detection rates of the SB and TB components were evaluated with a paired-sample analysis. Regression analyses were performed to predict AS-disqualification. RESULTS: A total of, 48.1% of patients diagnosed by 12-core TRUS-biopsy were disqualified from AS based on the MRI/TRUS-fusion biopsy results. In the initial fusion-biopsy cohort, upgrading occurred significantly less frequently during 2-year follow-up (20%, P<0.001). TBs alone were significantly superior compared with SBs alone to detect Gleason-score-upgrading. NPV for Gleason-upgrading was 93.5% for PIRADS⩽2. PSA level, PSA density, NIH-nomogram, initial PIRADS score (P<0.001 each) and PIRADS-progression on consecutive MRI (P=0.007) were significant predictors of AS-disqualification. CONCLUSIONS: Standard TRUS-biopsies lead to significant underestimation of PC under AS. MRI/TRUS-fusion biopsies, and especially the TB component allow more reliable risk classification, leading to a significantly decreased chance of subsequent AS-disqualification. Cancer detection with mpMRI alone is not yet sensitive enough to omit SB on follow-up after initial 12-core TRUS-biopsy. After MRI/TRUS-fusion biopsy confirmed AS, it may be appropriate to biopsy only those men with suspected progression on MRI.

Do we need new high-risk criteria for surgically treated renal cancer patients to improve the outcome of future clinical trials in the adjuvant setting? Results of a comprehensive analysis based on the multicenter CORONA database.

BACKGROUND: Since there is still an unmet need for potent adjuvant strategies for renal cancer patients with high progression risk after surgery, several targeted therapies are currently evaluated in this setting. We analyzed whether inclusion criteria of contemporary trials (ARISER, ASSURE, SORCE, EVEREST, PROTECT, S-TRAC, ATLAS) correctly identify high-risk patients. METHODS: The study group comprised 8873 patients of the international CORONA-database after surgery for non-metastatic renal cancer without any adjuvant treatment. Patients were divided into potentially eligible high-risk and assumable low-risk patients who didn't meet inclusion criteria of contemporary adjuvant clinical trials. The ability of various inclusion criteria for disease-free survival (DFS) prediction was evaluated by Harrell's c-index. RESULTS: During a median follow-up of 53 months 15.2% of patients experienced recurrence (5-year-DFS 84%). By application of trial inclusion criteria, 24% (S-TRAC) to 47% (SORCE) of patients would have been eligible for enrollment. Actual recurrence rates of eligible patients ranged between 29% (SORCE) and 37% (S-TRAC) opposed to <10% in excluded patients. Highest Hazard Ratio for selection criteria was proven for the SORCE-trial (HR 6.42; p < 0.001), while ASSURE and EVEREST reached the highest c-index for DFS prediction (both 0.73). In a separate multivariate Cox-model, two risk-groups were identified with a maximum difference in 5-year-DFS (94% vs. 61%). CONCLUSION: Results of contemporary adjuvant clinical trials will not be comparable as inclusion criteria differ significantly. Risk assessment according to our model might improve patient selection in clinical trials by defining a high-risk group (28% of all patients) with a 5-year-recurrence rate of almost 40%.