Fluorescence-guided laser lithotripsy: Estimation of the potential effectiveness and safety increase based on first clinical data.

In clinically approved laser lithotripsy systems, there is no automatic monitoring of fiber position to date. We investigated whether detecting stone autofluorescence, excited by a green aiming beam, is possible via the fiber during fragmentation by continuously recording the fluorescence signal in 12 ureterosopic lithotripsy procedures. We estimated which threshold the fluorescence signal's amplitude exceeds before laser pulses with visible stone removal by retrospective inspection of the endoscope's video data. For all procedures, blocking the laser when the fluorescence amplitude is below a threshold corresponding to the signal's baseline plus its range (maximum-minimum value) would have been appropriate to suppress ineffective pulses-the energy input could have been reduced by a mean of 14% (1%-29%) without changing the operation time. Ablation of the PTFE coating of the guidewire could have been prevented three times and cutting of a wire of the retrieval basket two times.

Deep, rapid, and durable prostate-specific antigen decline with apalutamide plus androgen deprivation therapy is associated with longer survival and improved clinical outcomes in TITAN patients with metastatic castration-sensitive prostate cancer.

BACKGROUND: The first interim analysis of the phase III, randomized, double-blind, placebo-controlled, multinational TITAN study demonstrated improved overall survival (OS) and radiographic progression-free survival (rPFS) with apalutamide added to ongoing androgen deprivation therapy (ADT) in patients with metastatic castration-sensitive prostate cancer. The final analysis confirmed improvement in OS and other long-term outcomes. We evaluated prostate-specific antigen (PSA) kinetics and the association between PSA decline and outcomes in patients with metastatic castration-sensitive prostate cancer from TITAN. PATIENTS AND METHODS: Patients received apalutamide (240 mg/day) or placebo plus ADT (1 : 1). This post hoc exploratory analysis evaluated PSA kinetics and decline in relation to rPFS (22.7 months' follow-up) and OS, time to PSA progression, and time to castration resistance (44.0 months' follow-up) in patients with or without confirmed PSA decline using a landmark analysis, the Kaplan-Meier method, and Cox proportional hazards model. RESULTS: One thousand and fifty-two patients (apalutamide, 525; placebo, 527) were enrolled. Best confirmed PSA declines (≥50% or ≥90% from baseline or to ≤0.2 ng/ml) were achieved at any time during the study in 90%, 73%, and 68% of apalutamide-treated versus 55%, 29%, and 32% of placebo-treated patients, respectively. By 3 months of apalutamide treatment, best deep PSA decline of ≥90% or to ≤0.2 ng/ml occurred in 59% and 51% of apalutamide- and in 13% and 18% of placebo-treated patients, respectively. Achievement of deep PSA decline at landmark 3 months of apalutamide treatment was associated with longer OS [hazard ratio (HR) 0.35; 95% confidence interval (CI) 0.25-0.48), rPFS (HR 0.44; 95% CI 0.30-0.65), time to PSA progression (HR 0.31; 95% CI 0.22-0.44), and time to castration resistance (HR 0.38; 95% CI 0.27-0.52) compared with no decline (P < 0.0001 for all). Similar results were observed at landmark 6 and 12 months of apalutamide treatment. CONCLUSIONS: Apalutamide plus ADT demonstrated a robust (rapid, deep, and durable) PSA decline that was associated with improved clinical outcomes, including long-term survival.

SAUL, a single-arm study of atezolizumab for chemotherapy-pretreated locally advanced or metastatic carcinoma of the urinary tract: outcomes by key baseline factors, PD-L1 expression and prior platinum therapy.

BACKGROUND: The impact of pretreatment factors on immune checkpoint inhibition in platinum-refractory advanced urothelial cancer (aUC) deserves further evaluation. The aim was to study the association of Bellmunt risk factors, time from last chemotherapy (TFLC), previous therapy and PD-L1 expression with atezolizumab efficacy in platinum-refractory aUC. PATIENTS AND METHODS: This was a post-hoc analysis of patients who had received prior cisplatin or carboplatin in the prospective, single-arm, phase IIIb SAUL study (NCT02928406). Patients were treated with 3-weekly atezolizumab 1200 mg intravenously. The primary outcome was overall survival (OS). Relationships were analysed using Cox regression and long-rank test. RESULTS: Of 997 patients in SAUL, 969 were eligible for this analysis. The number of Bellmunt risk factors was associated with OS (P < 0.001); median OS (mOS) for 0, 1 and 2-3 risk factors was 17.9, 8.9 and 3.3 months, respectively. Significant associations were also observed between OS and TFLC (P < 0.001), programmed death-ligand 1 (PD-L1) expression (P = 0.002), and prior perioperative chemotherapy (P = 0.013); mOS was 6.97 versus 11.63 months for TFLC ≤6 versus >6 months, 7.75 versus 11.6 months for PD-L1 expression on <1% of tumour-infiltrating immune cells (ICs) (IC0)/expression on 1% to <5% of tumour-infiltrating ICs (IC1) versus expression on ≥5% of tumour-infiltrating ICs (IC2/3) and 10.2 versus 7.8 months for prior versus no prior perioperative chemotherapy, respectively. The type of platinum compound and number of previous treatment lines were not associated with outcomes. CONCLUSIONS: Post-platinum atezolizumab is active in aUC, irrespective of previous platinum compound and lines of therapy. Bellmunt risk stratification, PD-L1 expression, TFLC and perioperative chemotherapy were identified as prognostic factors for OS with second-line atezolizumab, indicating the need for novel prognostic signatures for immunotherapy-treated patients with aUC.

Plasma tumor gene conversions after one cycle abiraterone acetate for metastatic castration-resistant prostate cancer: a biomarker analysis of a multicenter international trial.

BACKGROUND: Plasma tumor DNA fraction is prognostic in metastatic cancers. This could improve risk stratification before commencing a new treatment. We hypothesized that a second sample collected after one cycle of treatment could refine outcome prediction of patients identified as poor prognosis based on plasma DNA collected pre-treatment. PATIENTS AND METHODS: Plasma DNA [128 pre-treatment, 134 cycle 2 day 1 (C2D1), and 49 progression] from 151 chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC) patients in a phase II study of abiraterone acetate (NCT01867710) were subjected to custom targeted next-generation sequencing covering exons of these genes: TP53, AR, RB1, PTEN, PIK3CA, BRCA1, BRCA2, ATM, CDK12, CHEK2, FANCA HDAC2 and PALB2. We also captured 1500 pan-genome regions enriched for single nucleotide polymorphisms to allow detection of tumor DNA using the rolling B-allele method. We tested associations with overall survival (OS) and progression-free survival (PFS). RESULTS: Plasma tumor DNA detection was associated with shorter OS [hazard ratio (HR): 2.89, 95% confidence intervals (CI): 1.77-4.73, P ≤ 0.0001] and PFS (HR: 2.05; 95% CI: 1.36-3.11, P < 0.001). Using a multivariable model including plasma tumor DNA, patients who had a TP53, RB1 or PTEN gene alteration pre-treatment and at C2D1 had a significantly shorter OS than patients with no alteration at either time point (TP53: HR 7.13, 95% CI 2.37-21.47, P < 0.001; RB1: HR 6.24, 95% CI 1.97-19.73, P = 0.002; PTEN: HR 11.9, 95% CI 3.6-39.34, P < 0.001). Patients who were positive pre-treatment and converted to undetectable had no evidence of a difference in survival compared with those who were undetectable pre-treatment (P = 0.48, P = 0.43, P = 0.5, respectively). Progression samples harbored AR gain in all patients who had gain pre-treatment (9/49) and de novo AR somatic point mutations were detected in 8/49 patients. CONCLUSIONS: Plasma gene testing after one cycle treatment refines prognostication and could provide an early indication of treatment benefit.

[Treatment of metastatic, castration-resistant prostate cancer]. / Therapie des metastasierten kastrationsresistenten Prostatakarzinoms.

BACKGROUND: For many decades metastatic, castration-resistant prostate cancer (mCRPC) was thought to be treatment inaccessible. However, today, five drugs with significant life-prolonging effects are available in Germany, namely abiraterone, enzalutamide, docetaxel, cabazitaxel and radium-223. OBJECTIVE: The different treatment strategies in mCRPC are reviewed. MATERIALS AND METHODS: Landmark trials with supplementary information from Medline and abstracts of international congresses (ASCO; ASCO GU, ESMO) are summarized. RESULTS: The androgen receptor (AR)-targeting agents abiraterone and enzalutamide significantly prolong overall survival before and after docetaxel therapy. In addition, cabazitaxel can be applied secondary to docetaxel. Due to the low affinity of cabazitaxel to p­glycoprotein it remains active even if docetaxel has failed. The α­emitter radium-223 can be considered in third line therapy for symptomatic patients with bone limited disease only. In patients with castration resistance, a short prostate-specific antigen (PSA) doubling time but without metastases in conventional imaging apalutamide, darolutamide and enzalutamide significantly prolong metastasis-free survival. DISCUSSION: Prostate-specific membrane antigen (PSMA)-ligand therapy and novel targeting agents such as PARP inhibitors are promising new therapeutic modalities for mCRPC. Combination treatment strategies with immunotherapy are currently being evaluated in clinical trials. Based on the results of molecular analyses of tumor tissue as well as of circulating tumor cells and DNA, treatment of prostate cancer will be increasingly personalized in the future.

[Reports of prostate needle biopsies-what pathologists provide and urologists want]. / Befundbericht zu Prostatastanzbiopsien ­ was Pathologen liefern und Urologen wollen.

BACKGROUND: The prostate biopsy report is key for risk stratification of prostate cancer patients and subsequent therapeutic decision-making. However, due to the inclusion of a multitude of additional parameters its interpretation is becoming more challenging. OBJECTIVES: We aimed to determine how urologists currently interpret prostate biopsy reports, in particular how they consider different histopathological parameters for therapy decision-making. MATERIALS AND METHODS: A survey was sent to all urology practices in Germany with the help of the BDU (Berufsverband der Deutschen Urologen e. V.). In total, there were 106 complete responses that could be included for further analyses. RESULTS: Most urologists consider the number of positive cores and relative tumor burden (%) per core as crucial for the assessment of tumor extension. In case of targeted biopsies, the majority of urologists prefers a separate statement of positive cores per random biopsy scheme and per region of interest, respectively. The core with the highest Gleason score is mostly the basis for therapy decision-making (versus the overall Gleason score). Proportion of Gleason 4 pattern also seems to be critical for prostate cancer management. Only half of the urologists demand reporting of the new ISUP/WHO (International Society of Urological Pathology/World Health Organization) grade groups. Additional parameters claimed are Ki67, prostate-specific membrane antigen status, presence of intraductal or neuroendocrine component of the tumor. CONCLUSIONS: Our survey shows that there is no standardized reporting for prostate biopsies and that the interpretation of prostate biopsy reports varies among urologists. Further studies and guideline recommendations are necessary to establish a standardized reporting scheme for prostate biopsies.

[Rate of thrombosis and bleeding after urological surgery under standardized anticoagulation]. / Thromboserate und Blutungen in der universitären operativen Urologie unter standardisierter Antikoagulation.

BACKGROUND: According to the current definition of the German guideline for prevention of venous thromboembolism, urological surgery includes a high number of high-risk patients. All patients undergoing urological surgery between 2012 and 2016 were analyzed with regard to complications (bleeding or thrombosis). MATERIALS AND METHODS: This study is a retrospective and monocentric cohort study. Included were all patients who underwent surgery between 2012 and 2016 at the Urological Department at the University Hospital of Luebeck. Information was collected relating to anticoagulation, patient-specific and surgery-specific risk factors, and complications. RESULTS: In all, 3609 surgeries were analyzed: 77.8% of patients received no medical prophylaxis, 10.2% received an aggregation inhibitor, and 8.5% synthetic, unfractionated or low molecular weight heparin. Heparin was administered to 80.4% of patients after surgery. During an average hospital stay of 4.5 days, 93.3% of the patients received no change in anticoagulation. Merely 0.8% of all patients suffered from clinical thomboembolic events within 28 days. In contrast the number of bleedings was higher with 20.3% (minor: 4.8%, major: 15.5%). CONCLUSION: We found a slight risk for postoperative thromboembolism (0.8%). The risk for postoperative bleeding in contrast was 20.3%, including 15.5% major bleedings. The results are discussed in relation to the current guidelines.

The new ISUP 2014/WHO 2016 prostate cancer grade group system: first résumé 5 years after introduction and systemic review of the literature.

PURPOSE: To systematically and comprehensively review and summarize the most recent literature assessing the value of the new grading system introduced by the International Society of Urological Pathology (ISUP) in 2014 and accepted by the World Health Organization (WHO) in 2016. METHODS: A systematic literature search in the PubMed database was performed up to November 2018. Overall, 15 studies in the period from 2016 to 2018 evaluating the new grading system have been selected for evidence synthesis. RESULTS: The main goals of the new ISUP 2014/WHO 2016 grading system were to establish (I) a more accurate and simplified grade stratification, (II) less overtreatment of indolent prostate cancer as well as (III) an improved patient communication. The majority of the studies chose biochemical recurrence as an endpoint for evaluation and statistically assigns the new ISUP 2014/WHO 2016 grading system a higher prognostic accuracy than the former Gleason grading. However, in only a subset of studies it was clearly evident that the historical samples were not only re-grouped according to the new grade groups but also re-graded according to the new histomorphological 2014 ISUP criteria. CONCLUSIONS: The vast majority of the studies support an improved prognostic accuracy of the ISUP 2014/WHO 2016 grade groups and endorse its worldwide application.

[The impact of the androgen receptor splice variant AR-V7 on the prognosis and treatment of advanced prostate cancer]. / Bedeutung der Androgenrezeptor-Spleißvariante AR-V7 für Prognose und Therapie des fortgeschrittenen Prostatakarzinoms.

A recently discovered mechanism enabling prostate cancer cells to escape the effects of endocrine therapies consists in the synthesis of C-terminally truncated, constitutively active androgen receptor (AR) splice variants (AR-V). Devoid of a functional C-terminal hormone/ligand binding domain, various AR-Vs are insensitive to therapies targeting the androgen/AR signalling axis. Preliminary studies suggest that AR-V7, the most common AR-V, is a promising predictive tumour marker and a relevant selection marker for the treatment of advanced prostate cancer. This review critically outlines recent advances in AR-V7 diagnostics and presents an overview of current AR-V7 targeted therapies.

[Changes in the treatment of metastatic prostate cancer-new data and open questions]. / Therapie des metastasierten Prostatakarzinoms im Wandel ­ neue Daten und offene Fragen.

The availability of taxane-based chemotherapy and androgen-receptor-targeted agents (ARTAs) have significantly broadened the therapeutic options for patients with metastatic prostate cancer and may also result in longer patient survival. The therapeutic sequence of ARTAs and taxanes may influence outcome and therefore decisions should be made on an individual basis. This article provides guidance for therapeutic decision-making in daily clinical practice by working out criteria that can be used to support individual therapeutic decisions. The focus is on metastatic castration-naive prostate cancer, oligometastatic disease as well as non-metastatic and metastatic castration-resistant prostate cancer.

Substantial utilization of Facebook, Twitter, YouTube, and Instagram in the prostate cancer community.

PURPOSE: To measure the usage rate of social media (SoMe) resources in the prostate cancer community, we performed a comprehensive quantitative and qualitative assessment of SoMe activity on the topic of PCa on the four most frequented platforms. METHODS: We scanned the SoMe platforms Facebook, Twitter, YouTube, and Instagram for "prostate cancer" as a cross-sectional analysis or during a defined time period. Sources were included if their communication centered on PCa by title and content. We assessed activity measurements for each SoMe source and classified the sources into six functional categories. RESULTS: We identified 99 PCa-related Facebook groups that amassed 31,262 members and 90 Facebook pages with 283,996 "likes". On YouTube, we found 536 PCa videos accounting for 43,966,634 views, 52,655 likes, 8597 dislikes, and 12,393 comments. During a 1-year time period, 32,537 users generated 110,971 tweets on #ProstateCancer on Twitter, providing over 544 million impressions. During a 1-month time period, 638 contributors posted 1081 posts on Instagram, generating over 22,000 likes and 4,748,159 impressions. Among six functional categories, general information/support dominated the SoMe landscape on all SoMe platforms. CONCLUSION: SoMe activity on the topic of PCa on the four most frequented platforms is high. Facebook groups, YouTube videos, and Twitter tweets are mainly used for giving general information on PCa and education. High SoMe utilization in the PCa community underlines its future role for communication of PCa.

[Intravesical salpingiosis: case report and review of the literature]. / Intravesikale Salpingiose ­ Fallbericht und Literaturüberblick.

Endosalpingiosis of the urinary bladder is a rare benign condition characterised by the presence of ectopic endosalpingeal tissue in the bladder. If histology shows two or more Müllerian-derived components, this condition is referred to as Müllerianosis.To our knowledge less than 20 cases of Müllerianosis and 5 cases of endosalpingiosis have been documented in the literature.Although the pathogenesis remains unclear, two theories exist. The implantation theory assumes that Müllerian-derived tissue gets implanted in the wall of the urinary bladder during pelvic surgery. The second theory proposes a metaplastic origin of the disease.Patients suffering from endosalpingiosis or Müllerianosis may present with symptoms such as suprapubic pain, frequent urination, dysuria or gross haematuria, possibly with a cyclical appearance.We present the case of a 40-year-old female patient, who primarily presented with painful haematuria and was diagnosed with endosalpingiosis and treated by transurethral resection. Also we review the current literature.

[Inhibitors of the androgen receptor N­terminal domain : Therapies targeting the Achilles' heel of various androgen receptor molecules in advanced prostate cancer]. / Inhibitoren des Androgenrezeptor-N-Terminus' : Zielgerichtete Therapien gegen die Achillesferse verschiedener Androgenrezeptormoleküle im fortgeschrittenen Prostatakarzinom.

Although prostate cancer responds well to primary endocrine therapies, tumor progression with castration resistant tumor cells almost invariably occurs within a few years. Unfortunately, some CRPC patients do not respond to second-line therapies with abiraterone or enzalutamide. Moreover, patients who initially responded well to second-line hormone therapy develop resistance to abiraterone and/or enzalutamide within a short period of time. Besides an increase of intracellular androgen receptor (AR) levels, the predominant resistance mechanisms include AR aberrations (point mutations, AR splice variants) occurring predominantly at the androgen or ligand binding domain of the AR. The following review delineates recent progress in the development of AR inhibitors that do not depend on androgen binding and represent a putative third generation of AR inhibitors.

[En-bloc resection of bladder tumours (ERBT): current and future perspectives]. / Die En bloc-Resektion von Blasentumoren (ERBT) ­ eine Bestandsaufnahme.

Limitations inherent in the conventional transurethral resection of bladder tumours, the standard approach for diagnosis and treatment of bladder cancer, are well known: staging errors due to insufficient resection depth as well as intravesical tumour fragmentation, both of which make histopathological evaluation difficult. The purpose of this review is to present recent clinical data on the en-bloc resection of bladder tumours (ERBT), which has been demonstrated to offer a high potential to overcome these limitations. The recent findings show that ERBT provides a good resection quality with varying detection rates for tunica muscularis, which is a surrogate marker for resection quality regarding muscle-invasive tumours. ERBT can be performed using all energy sources. Available data show no relevant difference with regard to perioperative morbidity compared with cTURB. No conclusions can be drawn regarding the impact of ERBT on recurrence as the data are partly controversial. This has to be defined by further studies.

[Should cytoreductive nephrectomy be performed in patients with metastatic renal cell carcinoma and what is the scientific rationale?] / Wann ist bei eingetretener Metastasierung des Nierenkarzinoms die operative Entfernung des Primärtumors angezeigt und gibt es eine wissenschaftliche Grundlage dafür?

Between 15 and 20% of patients diagnosed with renal cell carcinoma suffer from metastatic disease by the time of diagnosis. In the immunotherapy era, the standard treatment was to perform cytoreductive nephrectomy (CN) followed by treatment with interferon α. This was based on two prospective randomized trials and their combined analysis. Since the introduction of targeted therapy, the use of CN came into question and the number of performed CN has declined. Two trials (CARMENA and SURTIME) evaluating the role of CN in the times of targeted therapy have either closed early or are recruiting slowly and will probably not be able to answer this question. Thus, we need to focus on retrospective data consisting of several analyses with large numbers of patients. These analyses all seem to show a benefit in overall survival, and adjusted for prognostic factors CN represents an independent predictor of longer survival. A correlation between expected life span and efficacy of CN has been shown with a survival rate that is three times higher after 3 years. Only patients with low performance status, low life expectancy, cerebral metastases, and old age did not benefit from CN. Furthermore, symptom control of large primary tumors without response to systemic therapy and the fact that all reports of long-term remission or long survival rates are associated with the use of CN are theoretical aspects speaking in favor of this treatment. This leads to the recommendation to perform CN in all patients with good performance status in all important guidelines.

[Focal dose escalation in the treatment of prostate cancer : Long-term results of HDR brachytherapy]. / Fokale Dosiseskalation in der Therapie des Prostatakarzinoms : Langzeitergebnisse der HDR-Brachytherapie.

BACKGROUND: We prospectively examined the effect and the safety of intensity-modulated HDR brachytherapy (IMBT) with focal dose escalation. MATERIALS AND METHODS: A total of 139 patients undergoing primary therapy for prostate cancer and 11 patients with recurrence were included. Data analysis focused on the following factors: date of primary diagnosis, Gleason score, initial prostate-specific antigen (PSA) value, PSA nadir, volume of the prostate in the transrectal ultrasound, biopsy of the prostate gland, androgen deprivation, chemotherapy, uroflowmetry, pre- and postoperative post-void residual urine (PVR), number of the needles in the prostate lobes and analysis of follow-up data. RESULTS: In the primary therapy group, 87.6 % of the patients had a PSA of 0-4 ng/ml at the time of follow-up, while in the recurrence group 81.8 % of patients were within this range. Overall, 55.8 % of patients in the primary group had a PSA nadir under 0.1 ng/ml, 37.2 % under 1 ng/ml, 5.8 % under 5 ng/ml and 1.2 % (1 patient) over 5 ng/ml. In the recurrence group, 100 % had a PSA nadir under 0.1 ng/dl. Fifty patients of the primary group reported grade 1 toxicity (Common Toxicity Criteria): 29 localized to the bladder and 21 to the rectum. Seventeen patients had grade 2 toxicity of the bladder and 1 patient had grade 3 toxicity of the bladder. Finally there was one grade 4 toxicity due to perforation of the sigmoid colon. In the recurrence group, 3 patients with grade 1 toxicity were observed (2 bladder and 1 bowl). Also 3 patients had grade 2 toxicity of the bladder, 1 patient had a grade 3 bladder toxicity and 1 patient had grade 4 toxicity due to bowl fistula. There were no grade 5 toxicities. CONCLUSION: The modifications of the "Kiel method" with focal dose escalation was proven as effective in locally advanced prostate carcinoma and in local recurrences of the disease with low level toxicity.