Diagnostic Utility of Artificial Intelligence-assisted Transperineal Biopsy Planning in Prostate Cancer Suspected Men: A Prospective Cohort Study.

BACKGROUND AND OBJECTIVE: Accurate magnetic resonance imaging (MRI) reporting is essential for transperineal prostate biopsy (TPB) planning. Although approved computer-aided diagnosis (CAD) tools may assist urologists in this task, evidence of improved clinically significant prostate cancer (csPCa) detection is lacking. Therefore, we aimed to document the diagnostic utility of using Prostate Imaging Reporting and Data System (PI-RADS) and CAD for biopsy planning compared with PI-RADS alone. METHODS: A total of 262 consecutive men scheduled for TPB at our referral centre were analysed. Reported PI-RADS lesions and an US Food and Drug Administration-cleared CAD tool were used for TPB planning. PI-RADS and CAD lesions were targeted on TPB, while four (interquartile range: 2-5) systematic biopsies were taken. The outcomes were the (1) proportion of csPCa (grade group ≥2) and (2) number of targeted lesions and false-positive rate. Performance was tested using free-response receiver operating characteristic curves and the exact Fisher-Yates test. KEY FINDINGS AND LIMITATIONS: Overall, csPCa was detected in 56% (146/262) of men, with sensitivity of 92% and 97% (p = 0.007) for PI-RADS- and CAD-directed TPB, respectively. In 4% (10/262), csPCa was detected solely by CAD-directed biopsies; in 8% (22/262), additional csPCa lesions were detected. However, the number of targeted lesions increased by 54% (518 vs 336) and the false-positive rate doubled (0.66 vs 1.39; p = 0.009). Limitations include biopsies only for men at clinical/radiological suspicion and no multidisciplinary review of MRI before biopsy. CONCLUSIONS AND CLINICAL IMPLICATIONS: The tested CAD tool for TPB planning improves csPCa detection at the cost of an increased number of lesions sampled and false positives. This may enable more personalised biopsy planning depending on urological and patient preferences. PATIENT SUMMARY: The computer-aided diagnosis tool tested for transperineal prostate biopsy planning improves the detection of clinically significant prostate cancer at the cost of an increased number of lesions sampled and false positives. This may enable more personalised biopsy planning depending on urological and patient preferences.

Antibiotic prophylaxis versus no antibiotic prophylaxis in transperineal prostate biopsies (NORAPP): a randomised, open-label, non-inferiority trial.

BACKGROUND: The benefit of antibiotic prophylaxis is uncertain when performing transperineal prostate biopsies. Judicious use of antibiotics is required as antimicrobial resistance increases worldwide. We aimed to assess whether antibiotic prophylaxis can be omitted when performing transperineal prostate biopsies under local anaesthesia as an outpatient procedure. METHODS: In this randomised, open-label, non-inferiority trial, we aimed to enrol all patients with a suspicion of prostate cancer undergoing transperineal prostate biopsies at two hospitals in Norway and Germany. Patients with a high risk of infection or ongoing infection were excluded. Patients were randomised (1:1) to receive intramuscular (in Norway) or intravenous (in Germany) 1·5 g cefuroxime antibiotic prophylaxis or not. Follow-up assessments were done after 2 weeks and 2 months. The primary outcome was rate of sepsis or urinary tract infections requiring hospitalisation within 2 months. The secondary outcome was the rate of urinary tract infections not requiring hospitalisation. These outcomes were assessed in all eligible randomly allocated participants with a prespecified non-inferiority margin of 4%. Biopsies were performed using an MRI-transrectal ultrasound fusion transperineal technique under local anaesthesia. Patients with a positive MRI underwent 2-4 biopsies per target; in addition, 8-12 systematic biopsies were performed in biopsy naive and MRI-negative patients. This study is registered with ClinicalTrials.gov, NCT04146142. FINDINGS: Between Nov 11, 2019, and Feb 23, 2021, 792 patients were referred for biopsy, of whom 555 (70%) were randomly allocated to treatment groups. 277 (50%) patients received antibiotic prophylaxis and 276 (50%) did not; two (<1%) patients were excluded after randomisation because of unknown allergy to study drug. Sepsis or urinary tract infections requiring hospitalisation occurred in no patients given antibiotic prophylaxis (0%, 95% CI 0 to 1·37) or not given antibiotic prophylaxis (0%, 0 to 1·37; difference 0% [95% CI -1·37 to 1·37]). Urinary tract infections not requiring hospitalisation occurred in one patient given antibiotic prophylaxis (0·36%, 95% CI 0·01 to 2·00) and three patients not given antibiotic prophylaxis (1·09%, 0·37 to 3·15; difference 0·73% [95% CI -1·08 to 2·81]). The number needed to treat with antibiotic prophylaxis to avoid one infection was 137. INTERPRETATION: The non-inferiority margin of 4% was not exceeded, suggesting rates of infections were not higher in patients not receiving antibiotic prophylaxis before transperineal prostate biopsy than in those receiving it. Therefore, antibiotic prophylaxis might be omitted in this population. FUNDING: Oslo University Hospital, Oslo, Norway and Vivantes Klinikum Am Urban, Berlin, Germany.

Evaluation of systematic prostate biopsies when performing transperineal MRI/TRUS fusion biopsy with needle tracking-what is the additional value?

PURPOSE: To evaluate the additional value of systematic biopsies (SB) when performing transperineal MRI/TRUS fusion biopsies (MRI/TRUS TPBx) with needle tracking. METHODS: From January 2019 to March 2021 969 Patients after a MRI/TRUS TPBx were evaluated separately for target biopsies (TB) and systematic biopsies regarding PCa detection and PCa risk evaluation. Needle tracking in the axial sequences of multiparametric MRI was used to assess the localisation of the detected PCa in the biopsy cores related to the reported PI-RADS lesions. RESULTS: The overall cancer detection rate (CDR) for PCa and clinically significant (cs) PCa (ISUP ≥2) with the combination of TB and SB were 66 and 49%. TB detected 46% csPCa and SB 22% csPCa. SB identified 1.5% additional csPCa outside of the reported PI-RADS lesions. 16 patients (1.7%) showed a relevant upgrading from clinically insignificant PCa in TB to csPCa. In 736 patients with unilateral suspicious lesions on MRI, 145 patients (20%) were detected with contralateral PCa-positive SB. 238 patients (25%) showed PCa positive systematic biopsy cores outside of the described PI-RADS lesions. CONCLUSIONS: Needle tracking optimizes the 3D-localisation of cancer in the prostate. Our results show that the added value of SB with a reduced systematic biopsy scheme is low with regard to prostate cancer (PCa) detection and PCa risk evaluation. However, there is a relevant added value for localizing multifocal PCa in the primary diagnostic by a MRI/TRUS fusion biopsy of the prostate.

[The Onkonet database: taking stock of an Internet-based, multi-centre database on surgical prostate cancer treatment]. / Die Onkonet-Datenbank: Bilanz einer Internet-basierten, multizentrischen Dokumentationsplattform zur Erfassung der operativen Therapie des Prostatakarzinoms.

BACKGROUND: The Onkonet database has been developed and coordinated by the Berliner Tumorzentrum e. V. (http://www.prostata-ca.net) and contains data on pre-, peri- and postoperative parameters of radical prostatectomy documented since January 2005. With its user-friendly interface and its integrated benchmarking tool, the main goal of Onkonet was to outline and improve the surgical care of prostate cancer patients in Germany. This study aimed to analyse all Onkonet data documented from the beginning of the project until June 2018. We focused on the completeness and plausibility of data to investigate and define the possibilities and limits of further analyses. PATIENTS AND METHODS: All patients who underwent radical prostatectomy in one of the urological clinics participating in this project until June 2018 were included in this retrospective study. The completeness of all documented patient data was analysed using Excel 2013. The statistical analysis was descriptive. RESULTS: A total of 21 474 patients were documented in Onkonet. 58,6 % (12 591) of them had a complete dataset including date of birth, date of surgery, dates of hospitalisation and discharge, initial PSA value, Gleason score of the biopsy, clinical T stage, pathological T stage, pathological Gleason score, as well as information on the surgical technique. Mean completeness of pre-operative parameters was 26,8 %, of hospitalisation parameters 64,5 %, and of pathological parameters 58,1 %. Amongst these, the documentation of the pathological T stage was complete in 80,1 %, documentation of N stage in 78,8 %, of M stage in 74,8 %, of pathological Gleason Score in 78,7 %, and of R1 status in 78,7 %. Completeness of follow-up data was 8,1 %, with PSA data being available in 27,2 %, continence data in 23,0 %, and potency data in 13,9 %. CONCLUSIONS: Comprising 21 474 documented patients and over 200 parameters, Onkonet is one of the most comprehensive clinical registers for the documentation of prostate cancer patients in Germany. The data analysis showed that the limitations of such a database are mainly due to the high number of parameters and the high susceptibility to errors due to manual data submission.

Illness representations, coping and anxiety among men with localized prostate cancer over an 18-months period: A parallel vs. level-contrast mediation approach.

OBJECTIVE: Men diagnosed with localized prostate cancer (lPCa) are confronted with the decision for a treatment strategy, potentially experiencing treatment side effects and psychological distress. The Common Sense Model proposes that coping with such challenges is related to illness representations: Beliefs regarding consequences, coherence, timeline, and controllability of the illness. We analyzed the interplay of illness representations, coping and anxiety over an 18-month period among men with lPCa undergoing different treatment options (Active Surveillance, curative treatment). METHODS: In this longitudinal study, 183 men (age M = 66.83) answered a questionnaire before starting treatment, and 6, 12, and 18 months later. We analyzed time trajectories with growth curve modeling and conducted mediation analyses to evaluate the influence of coping on the association of illness representations and anxiety. Using a novel methodological approach, we compared a classic parallel mediation model with a level-contrast approach for the correlated mediators problem- and emotion-focused coping. RESULTS: Independent of treatment (b = 1.31, p = 0.200) men reported an elevated level of anxiety after diagnosis which declined considerably within the following 6 months (b = -1.87, p = 0.009). The perceived seriousness of consequences was significantly associated with greater anxiety, at baseline (ß = 0.471) and over time (all ß ≥ 0.204). This association was mediated by coping: Using more emotion-than problem-focused coping was associated with higher anxiety. CONCLUSIONS: Receiving a lPCa diagnosis is associated with a phase of increased anxiety. In order to reduce anxiety, information provision should be accompanied by developing concrete action plans to enable problem-focused coping strategies.

Multicenter transperineal MRI-TRUS fusion guided outpatient clinic prostate biopsies under local anesthesia.

INTRODUCTION: Transperineal Prostate biopsies (TPBx) are usually performed under general anesthesia without image fusion. This study aimed to evaluate prostate cancer (Pca) detection rates (CDR), pain, and adverse events using a novel, free-hand TPBx technique, based on elastic fusion of magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) under local anesthesia. MATERIALS AND METHODS: This multicenter retrospective study included all consecutive patients scheduled for a TPBx. All had clinical suspicion of Pca, active surveillance scheduled for a re-biopsy, or suspicion of local recurrence after previous treatment. Bi-parametric or multiparametric MRI was performed in all patients and classified as positive in the case of Prostate Imaging-Reporting and Data System (PIRADS) suspicion ≥3. At least 1 targeted TPBx was realized from each PIRADS ≥3 index lesion. Six to 12 systematic random TPBx were done in patients with negative MRI. All biopsies were performed under local anesthesia in an outpatient clinic with MRI-TRUS fusion and the 3D navigation system Trinity Perine (Koelis, France). Any- and clinically significant Pca (csPca) (ISUP gr. ≥2) was recorded. Biopsy-related pain and adverse events were reported according to a visual analogue score of 0-10. RESULTS: In total, 377 patients were included for analyses. The mean age was 67 years (95% Confidence Interval: 66-68) and the median prostate-specific antigen was 7.2 ng/ml (interquartile range [IQR] 4.8-11.0). MRI was negative in 6% and positive in 94%. The median MRI prostate volume was 43 ml (IQR 31-60) and the median MRI index tumor volume was 0.9 ml (IQR 0.5-2.1). The median number of TPBx was 4 (IQR 3-4). The overall detection of any- and csPca was 64% and 52%, respectively. The overall CDR according to PIRADS 3, 4, and 5 was 30%, 70%, and 94%, respectively. In patients with negative MRI, any- and csPca was detected in 23% and 9%, respectively. The median visual analogue score score was 2 (IQR 1-3, range 0-7). Two patients (0.5%) developed postbiopsy infection, of which one developed urosepsis. Treatment requiring haematuria or urinary retention did not occur. CONCLUSION: Free-hand MRI/TRUS fusion-guided and systematic random TPBx in LA is a feasible, safe, and well-tolerated technique for diagnosing Pca.

Robot-Assisted versus Laparoscopic Donor Nephrectomy: A Comparison of 250 Cases.

Living kidney donation is the best treatment for end-stage renal disease, however, the best surgical approach for minimally-invasive donor nephrectomy (DN) is still a matter of debate. This bi-centric study aimed to retrospectively compare perioperative outcomes and postoperative kidney function after 257 transperitoneal DNs including 52 robot-assisted (RDN) and 205 laparoscopic DNs (LDN). As primary outcomes, the intraoperative (operating time, warm ischemia time (WIT), major complications) and postoperative (length of stay, complications) results were compared. As secondary outcomes, postoperative kidney and graft function were analyzed including delayed graft function (DGF) rates, and the impact of the surgical approach was assessed. Overall, the type of minimally-invasive donor nephrectomy (RDN vs. LDN) did not affect primary outcomes, especially not operating time and WIT; and major complication and DGF rates were low in both groups. A history of smoking and preoperative kidney function, but not the surgical approach, were predictive for postoperative serum creatinine of the donor and recipient. To conclude, RDN and LDN have equivalent perioperative results in experienced centers. For this reason, not the surgical approach, but rather the graft- (preoperative kidney function) and patient-specific (history of smoking) aspects impacted postoperative kidney function.

Analysis of quality of life and late biochemical predictors for localized cancer recurrence following radical prostatectomy.

BACKGROUND: Patients with localized prostate cancer (PCa) experience biochemical recurrence (BCR) despite a curatively intended radical prostatectomy (RP). The aim of this study was to describe the quality of life (QoL) of patients with a BCR while identifying predictors of early (ER) and late recurrence (LR). METHODS: For this purpose, a total of 330 PCa patients with a BCR following RP at Charité University Hospital in Berlin were analyzed. BCR was defined as two consecutive PSA values ≥ 0.2 after a previous non-detectable level. LR was defined as a BCR after 3 years post-RP. Differences in overall survival (OS) were calculated using the log-rank testing. A logistic regression model was applied to identify predictors of ER and LR. We further evaluated difference between ER and LR with respect to functional outcomes in urinary and sexual domains as well as the patients QoL. RESULTS: Out of 330 patients, 180 patients showed late BCR. Patients rated their global QoL with 64.5% in ER and 68.8% LR as good (EORTC quality of life Questionnaire, question 29 and 30). The questionnaire did not reveal QoL differences in terms of sexual and urinary function within ER and LR. The main predictor for LR was preoperative serum prostate-specific antigen (PSA) levels with a relative risk (RR) of 0.96 (p = 0.011). OS for patients with LR was significant longer than for patients with ER (154.3 vs. 143.2 months, p = 0.018). CONCLUSION: Patients with a BCR show a good quality of life possibly irrespective of the time point of BCR. We further identified preoperative PSA levels as a predictor of LR and noted that patients with LR patients lived longer. Further studies are needed.

[A retrospective analysis of functional and oncologic outcomes following surgical treatment of patients with pT1/pT2 renal cell carcinoma at a tertiary referral centre]. / Peri- und postoperatives Ergebnis nach Nierentumorchirurgie bei pT1/pT2 Nierenzellkarzinom ­ eine retrospektive Zentrumsanalyse der funktionellen und onkologischen Ergebnisse.

INTRODUCTION: In patients with localised renal cell carcinoma, the only curative treatment option is surgical tumour excision. The aim of this study was to evaluate peri- and postoperative outcomes as well as oncologic and functional long-term results following surgical treatment of patients with renal cell carcinoma (pT1/pT2) at a tertiary referral centre. PATIENTS AND METHODS: This retrospective study included a total of 758 patients with localised renal cell carcinoma (pT1 /pT2), who underwent radical (RN) or partial (PN) nephrectomy between 01/2008 and 10/2014. Pre-, peri- and postoperative parameters were recorded. Oncologic and functional long-term data were retrieved through questionnaires and structured telephone interviews. RESULTS: Laparoscopic RN or PN resulted in less blood loss and lower peri- and postoperative complication rates compared to open procedures. Regarding short- and long-term renal function, a higher increase in serum creatinine levels was detected after RN. No difference was noted in health status and quality of life. Median follow-up was 36 months. A total of 10.4 % of patients died during follow-up. 4.7 % and 8.4 % developed a relapse or metastatic disease. No difference was found between laparoscopic and open RN/PNs in terms of oncologic long-term results. DISCUSSION: In conclusion, all surgical techniques evaluated in this study provided good oncologic and functional short-/long-term outcomes.

The importance of sexuality, changes in erectile functioning and its association with self-esteem in men with localized prostate cancer: data from an observational study.

BACKGROUND: Treatment for localized prostate cancer (PCa) can cause long-term changes in erectile functioning. However, data on the importance of sexuality and possible consequences of altered erectile functioning on self-esteem in men with localized PCa are lacking. METHODS: Self-report questionnaires were completed by 292 men with PCa, initially managed with active surveillance (AS) or radical prostatectomy (RP). Independent t-tests were conducted to evaluate group differences. A sequential multiple regression model was fitted to analyze the associations between the importance of sexuality, changes in erectile functioning and impairment of self-esteem. Interaction effects were tested using simple slope analyses. RESULTS: Participants were 70 ± 7.2 years old and 66.5% rated sex as being "rather/very important". The two groups differed markedly in changes in erectile functioning, importance of sexuality and impairment of self-esteem (p < .001), with higher values in RP patients. Regression analysis showed that after adjustment for control variables and importance of sexuality, changes in erectile functioning were still associated with impairment of self-esteem (B = .668, SE = .069, p < .001). The interaction of changes in erectile functioning and importance of sexuality reached significance (B = .318, SE = .062, p < .001). CONCLUSIONS: RP patients report more changes in erectile functioning than AS patients. Moreover, in men with localized PCa, erectile functioning and self-esteem are closely related. Sexuality seems to be important for the majority of these men. Physicians should address the possibility of erectile dysfunction and its potential effects on psychological well-being before the treatment decision.

Phase III Trial of Adjuvant Sunitinib in Patients with High-Risk Renal Cell Carcinoma: Exploratory Pharmacogenomic Analysis.

PURPOSE: In the S-TRAC trial, adjuvant sunitinib prolonged disease-free survival (DFS) versus placebo in patients with loco-regional renal cell carcinoma at high risk of recurrence after nephrectomy. An exploratory analysis evaluated associations between SNPs in several angiogenesis- or hypoxia-related genes and clinical outcomes in S-TRAC. PATIENTS AND METHODS: Blood samples were genotyped for 10 SNPs and one insertion/deletion mutation using TaqMan assays. DFS was compared using log-rank tests for each genotype in sunitinib versus placebo groups and between genotypes within each of three (sunitinib, placebo, and combined sunitinib plus placebo) treatment groups. P values were unadjusted. RESULTS: In all, 286 patients (sunitinib, n = 142; placebo, n = 144) were genotyped. Longer DFS [HR; 95% confidence interval (CI)] was observed with sunitinib versus placebo for VEGFR1 rs9554320 C/C (HR 0.44; 95% CI, 0.21-0.91; P = 0.023), VEGFR2 rs2071559 T/T (HR 0.46; 95% CI, 0.23-0.90; P = 0.020), and eNOS rs2070744 T/T (HR 0.53; 95% CI, 0.30-0.94; P = 0.028). Shorter DFS was observed for VEGFR1 rs9582036 C/A versus C/C with sunitinib, placebo, and combined therapies (P ≤ 0.05), and A/A versus C/C with sunitinib (P = 0.022). VEGFR1 rs9554320 A/C versus A/A was associated with shorter DFS in the placebo (P = 0.038) and combined (P = 0.006) groups. CONCLUSIONS: Correlations between VEGFR1 and VEGFR2 SNPs and longer DFS with sunitinib suggest germline SNPs are predictive of improved outcomes with adjuvant sunitinib in patients with renal cell carcinoma. Independent validation studies are needed to confirm these findings.

Influences of Surgical Volume on Perioperative and Oncological Outcomes Following Radical Prostatectomy.

INTRODUCTION: The purpose of this study was to evaluate whether the number of radical prostatectomies per hospital per year is associated with stage distribution, surgical techniques or quality related outcome in Germany. MATERIALS AND METHODS: A German Internet-based database was analyzed. Hospitals were categorized according to their yearly radical prostatectomy (RP) volume. Patient's characteristics, RP techniques, and outcome-related parameters were compared between the different hospital volume categories. RESULTS: A total of 6,447 patients were analyzed. The highest rate of organ-confined disease and the lowest rate of extracapsular invasion have been demonstrated in very low-volume centres (72.6%

Validation of the 16-Gene Recurrence Score in Patients with Locoregional, High-Risk Renal Cell Carcinoma from a Phase III Trial of Adjuvant Sunitinib.

Purpose: Adjuvant sunitinib prolonged disease-free survival (DFS; HR, 0.76) in patients with locoregional high-risk renal cell carcinoma (RCC) in the S-TRAC trial (ClinicalTrials.gov NCT00375674). The 16-gene Recurrence Score (RS) assay was previously developed and validated to estimate risk for disease recurrence in patients with RCC after nephrectomy. This analysis further validated the prognostic value of RS assay in patients from S-TRAC and explored the association of RS results with prediction of sunitinib benefit.Patients and Methods: The analysis was prospectively designed with prespecified genes, algorithm, endpoints, and analytical methods. Primary RCC was available from 212 patients with informed consent; primary analysis focused on patients with T3 RCC. Gene expression was quantitated by RT-PCR. Time to recurrence (TTR), DFS, and renal cancer-specific survival (RCSS) were analyzed using Cox proportional hazards regression.Results: Baseline characteristics were similar between patients with and those without RS results, and between the sunitinib and placebo arms among patients with RS results. RS results predicted TTR, DFS, and RCSS in both arms, with the strongest results observed in the placebo arm. When high versus low RS groups were compared, HR for recurrence was 9.18 [95% confidence interval (CI), 2.15-39.24; P < 0.001) in the placebo arm; interaction of RS results with treatment was not significant.Conclusions: The strong prognostic performance of the 16-gene RS assay was confirmed in S-TRAC, and the RS assay is now supported by level IB evidence. RS results may help identify patients at high risk for recurrence who may derive higher absolute benefit from adjuvant therapy. Clin Cancer Res; 24(18); 4407-15. ©2018 AACR.

Intermittent vs continuous docetaxel therapy in patients with metastatic castration-resistant prostate cancer - a phase III study (PRINCE).

OBJECTIVE: To investigate non-inferiority of intermittent docetaxel compared to continuous docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC). PATIENT AND METHODS: The investigator initiated randomised phase III study included 187 chemotherapy-naïve patients with mCRPC who were allocated to two treatment arms: intermittent docetaxel and continuous docetaxel. Docetaxel was applied in both arms as weekly (35 mg/m2 ) or 3-weekly (75 mg/m2 ). The primary endpoint was 1-year survival, which was tested for non-inferiority (margin δ = 0.125). The secondary endpoints were: overall survival (OS), progression-free survival (PFS), median time to treatment failure (TTF), and toxicity. RESULTS: Of 156 eligible patients, 78 were allocated to each arm. The intermittent treatment met the non-inferiority criteria for 1-year survival (two-sided 95% confidence interval, -0.12, 18, P = 0.022), but not for OS, according to the result of a post hoc analysis. The differences between the study arms in PFS and TTF were not significant. The median (range) treatment holiday in the intermittent arm was 110 (13-486) days, or 38% of the overall treatment duration. Safety profiles of both study arms were comparable. The main limitation of this study was that the planned number of patients could not be recruited. CONCLUSION: Intermittent docetaxel chemotherapy was non-inferior to continuous therapy for 1-year survival; non-inferiority in regard to OS was not reached.

Immune Biomarkers Predictive for Disease-Free Survival with Adjuvant Sunitinib in High-Risk Locoregional Renal Cell Carcinoma: From Randomized Phase III S-TRAC Study.

Purpose: Adjuvant sunitinib therapy compared with placebo prolonged disease-free survival (DFS) in patients with locoregional high-risk renal cell carcinoma (RCC) in the S-TRAC trial (ClinicalTrials.gov number NCT00375674). A prospectively designed exploratory analysis of tissue biomarkers was conducted to identify predictors of treatment benefit.Experimental Design: Tissue blocks were used for immunohistochemistry (IHC) staining of programmed cell death ligand 1 (PD-L1), CD4, CD8, and CD68. DFS was compared between < versus ≥ median IHC parameter using the Kaplan-Meier method. For biomarkers with predictive potential, receiver operating characteristics curves were generated.Results: Baseline characteristics were similar in patients with (n = 191) and without (n = 419) IHC analysis. Among patients with IHC, longer DFS was observed in patients with tumor CD8+ T-cell density ≥ versus < median [median (95% CI), not reached (6.83-not reached) versus 3.47 years (1.73-not reached); hazard ratio (HR) 0.40 (95% CI, 0.20-0.81); P = 0.009] treated with sunitinib (n = 101), but not with placebo (n = 90). The sensitivity and specificity for CD8+ T-cell density in predicting DFS were 0.604 and 0.658, respectively. Shorter DFS was observed in placebo-treated patients with PD-L1+ versus PD-L1- tumors (HR 1.75; P = 0.103). Among all patients with PD-L1+ tumors, DFS was numerically longer with sunitinib versus placebo (HR 0.58; P = 0.175).Conclusions: Greater CD8+ T-cell density in tumor tissue was associated with longer DFS with sunitinib but not placebo, suggesting predictive treatment effect utility. Further independent cohort validation studies are warranted. The prognostic value of PD-L1 expression in primary tumors from patients with high-risk nonmetastatic RCC should also be further explored. Clin Cancer Res; 24(7); 1554-61. ©2018 AACR.

Adjuvant Sunitinib for High-risk Renal Cell Carcinoma After Nephrectomy: Subgroup Analyses and Updated Overall Survival Results.

BACKGROUND: Adjuvant sunitinib significantly improved disease-free survival (DFS) versus placebo in patients with locoregional renal cell carcinoma (RCC) at high risk of recurrence after nephrectomy (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59-0.98; p=0.03). OBJECTIVE: To report the relationship between baseline factors and DFS, pattern of recurrence, and updated overall survival (OS). DESIGN, SETTING, AND PARTICIPANTS: Data for 615 patients randomized to sunitinib (n=309) or placebo (n=306) in the S-TRAC trial. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Subgroup DFS analyses by baseline risk factors were conducted using a Cox proportional hazards model. Baseline risk factors included: modified University of California Los Angeles integrated staging system criteria, age, gender, Eastern Cooperative Oncology Group performance status (ECOG PS), weight, neutrophil-to-lymphocyte ratio (NLR), and Fuhrman grade. RESULTS AND LIMITATIONS: Of 615 patients, 97 and 122 in the sunitinib and placebo arms developed metastatic disease, with the most common sites of distant recurrence being lung (40 and 49), lymph node (21 and 26), and liver (11 and 14), respectively. A benefit of adjuvant sunitinib over placebo was observed across subgroups, including: higher risk (T3, no or undetermined nodal involvement, Fuhrman grade ≥2, ECOG PS ≥1, T4 and/or nodal involvement; hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.55-0.99; p=0.04), NLR ≤3 (HR 0.72, 95% CI 0.54-0.95; p=0.02), and Fuhrman grade 3/4 (HR 0.73, 95% CI 0.55-0.98; p=0.04). All subgroup analyses were exploratory, and no adjustments for multiplicity were made. Median OS was not reached in either arm (HR 0.92, 95% CI 0.66-1.28; p=0.6); 67 and 74 patients died in the sunitinib and placebo arms, respectively. CONCLUSIONS: A benefit of adjuvant sunitinib over placebo was observed across subgroups. The results are consistent with the primary analysis, which showed a benefit for adjuvant sunitinib in patients at high risk of recurrent RCC after nephrectomy. PATIENT SUMMARY: Most subgroups of patients at high risk of recurrent renal cell carcinoma after nephrectomy experienced a clinical benefit with adjuvant sunitinib. TRIAL REGISTRATION: ClinicalTrials.gov NCT00375674.

Complications, functional and quality of life outcomes following primary and secondary implantation of penile prosthesis at a tertiary referral center.

The implantation of a penile prosthesis (PP) may be recommended in patients with severe erectile dysfunction (ED) who do not respond to conservative treatments. The aim of this study was to evaluate complications, as well as functional and quality of life outcomes following primary and secondary implantation of PP at a tertiary referral center. In this retrospective study, a total of 51 patients (41 patients with primary (PPP) and 10 with secondary PP (SPP)) were included. Patients and operative characteristics were recorded and complications were analyzed using the Clavien-Dindo classification. To evaluate satisfaction of patients and their partners, as well as PP long-term function, follow-up data were collected by using questionnaires (Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) and QLQC30). Fifty-one patients with a median age of 61 years (IQR 52-68) received PP implantation (44 AMS 700, 7 Coloplast Titan). Main causes of ED were after radical prostatectomy (27.5%), diabetes (21,6%), and other unknown reasons (43.1%). Median time of intervention was 94.5 min (IQR 80.8-110.3) with no significant difference between PPP and SPP. Only one patient undergoing PPP surgery had grade 3 complication. Follow-up data from a total of 43 patients (84.3%) with a median follow-up of 26 months (IQR 17-41 mo) was recorded. At the time of follow-up, 88.4% of the PPs were still functional (PPP n = 34 (94.4%), SPP n = 4 (57.1%), p = 0.024). Overall estimated mean PP survival was 63.0 mo ((95% CI) 56.2-70.8 mo) with no significant difference between PPP and SPP. Overall satisfaction (EDITS und QLQC30) was high in both groups with no significant difference. PP implantation shows to be a safe treatment option in the management of severe ED.

[The use of partial nephrectomy in the treatment of patients with pT1/pT2 renal cell carcinoma: a trend analysis from a tertiary referral centre]. / Anwendung der organerhaltenden Nierentumorchirurgie in der Behandlung von Patienten mit Nierenzellkarzinom im Stadium pT1/pT2 ­ eine unizentrische Trendanalyse.

INTRODUCTION: In patients with localised renal cell carcinoma, the only curative treatment option is surgical tumour excision. Current national and European guidelines recommend partial nephrectomy in the form of an open or minimally-invasive procedure in case of small tumours. The aim of this study was to examine the use of radical (RN) or partial (PN) nephrectomy performed as open or minimally-invasive procedures in patients with pT1 /pT2 renal cell carcinoma at a tertiary referral centre. PATIENTS AND METHODS: This retrospective study included a total of 758 patients with localised renal cell carcinoma (pT1/pT2), who underwent PN or RN between 01/2008 and 10/2014. Nephrectomy was either performed as an open (OPN, ORN), laparoscopic (LPN, LRN) or robot-assisted laparoscopic (RAPN) procedure. RESULTS: Out of 758 patients, 439 (57.9 %) underwent PN performed as an LPN in n = 254 (57.9 %) and OPN in n = 185 (42.1 %). 319 patients (42.1 %) underwent RN performed as an LRN in n = 250 (78.4 %) and ORN in n = 69 (21.6 %). Between 2008 and 2014, there was a trend towards the use of PN, especially in patients with pT1a and pT1b. The majority of patients with pT2 underwent RN, performed as an LRN in 40 - 53.9 %. DISCUSSION: The results of this trend analysis from a tertiary referral centre demonstrate an increased use of PN and minimally-invasive procedures over time, as recommend by national and European guidelines.

The Effect of Evolving Strategies in the Surgical Management of Organ-Confined Prostate Cancer: Comparison of Data from 2005 to 2014 in a Multicenter Setting.

INTRODUCTION: The objective of this study was to evaluate changes of patient characteristics and surgical techniques in radical prostatectomy in Germany within the last decade. METHODS: Data from 44 German prostate cancer centers were included in the study. Patients' characteristics (age, initial PSA value), surgical techniques (open vs. minimally invasive approaches), perioperative parameters (operating time, rate of nerve-sparing (NS) radical prostatectomies (RPs), hospitalization time, catheter indwelling time, surgical margin status, number of dissected lymph nodes (LN)), and pathological findings (tumor stage, Gleason score) were analyzed. RESULTS: Data from 11,675 patients who underwent RP between 2005 and 2014 were analyzed. The rate of open RP approaches decreased by 1.7% (p = 0.0164), the rate of minimally invasive approaches increased by 1.8% (p = 0.0164). Robot-assisted RPs (RARP) increased by 4.6% (p < 0.0001). The number of NS procedures and pelvic lymphadenectomy (LA) increased by 4.5% (p < 0.0001) and 4.7% (p < 0.0001), respectively. Catheter indwelling time and hospitalization time decreased by 1 day (p < 0.0001). No change in the rate of positive surgical margins (p = 0.5061) and the ratio of positive lymph nodes removed (p = 0.4628) was observed. The number of Gleason ≤6 tumors decreased significantly (p < 0.0001). CONCLUSIONS: The number of RARP has significantly increased over the past decade and there is a trend towards surgeries on more advanced tumors with higher yields of lymph nodes dissected. At the same time, the rate of nerve-sparing procedures has significantly increased.