Preoperative fibrinogen/CRP score predicts survival in upper urothelial tract carcinoma patients undergoing radical curative surgery

Purpose Upper tract urothelial carcinoma (UTUC) represents an often aggressive malignancy associated with poor prognosis. Therefore, finding reliable prognostic biomarkers in patients undergoing curative surgery for improved risk stratification is crucial. We evaluated the prognostic value of the Fibrinogen/C-reactive protein (FC)-score in a cohort of surgically treated UTUC patients. Methods 170 patients with radiologically and histologically verified UTUC who underwent radical curative surgery between 1990 and 2020, were included. The FC-score was calculated for each patient, with patients receiving 1 point each if Fibrinogen and/or CRP levels were elevated above the 25th or 75th percentile, respectively. Patients were divided into three subgroups according to their FC-score of 0, 1 or 2 point(s). Kaplan–Meier analysis, uni- and multivariable Cox proportional hazard models were implemented. We determined cancer-specific survival (CSS) as primary endpoint, whereas overall survival (OS) and recurrence-free survival (RFS) were considered secondary endpoints. Results High FC-score (2 points) was significantly associated with adverse histological features such as vascular invasion (OR = 4.08, 95%CI 1.18–14.15, p = .0027) and tumour necrosis (OR = 6.67, 95%CI 1.35–32.96, p = 0.020). Both, uni- and multivariable Cox proportional hazard models showed the FC-score as a significant predictor for CSS (univariable analysis: FC-score = 1: HR = 1.90, 95%CI 0.92–3.93, p = 0.085 | FC-score = 2: HR = 2.86, 95%CI 1.22–6.72, p = 0.016). Furthermore, in univariable analysis, patients with higher FC-score had significantly shorter OS (FC-score = 1: HR = 1.32, 95%CI 0.70–2.49, p = 0.387 | FC-score = 2: HR = 2.19, 95%CI 1.02–4.67, p = 0.043). However, this did not prevail in multivariable analysis. Conclusion The FC-score represents a novel potential biomarker in patients with UTUC undergoing radical curative surgery

Patterns of peripheral blood B-cell subtypes are associated with treatment response in patients treated with immune checkpoint inhibitors: a prospective longitudinal pan-cancer study

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized systemic anti-tumor treatments across different types of cancer. Nevertheless, predictive biomarkers regarding treatment response are not routinely established yet. Apart from T-lymphocytes, the humoral immunity of B-lymphocytes is studied to a substantially lesser extent in the respective setting. Thus, the aim of this study was to evaluate peripheral blood B-cell subtypes as potential predictors of ICI treatment response. METHODS: Thirty-nine cancer patients receiving ICI therapy were included into this prospective single-center cohort study. All had a first blood draw at the date before treatment initiation and a second at the time of first response evaluation (after 8-12 weeks). Seven different B-cell subtypes were quantified by fluorescence-activated cell sorting (FACS). Disease control- (DCR) and objective response rate (ORR) were co-primary study endpoints. RESULTS: Overall, DCR was 48.7% and ORR was 25.6%, respectively. At baseline, there was no significant association of any B-cell subtype with neither DCR nor ORR. At the first response evaluation, an increase in the frequency of CD21(-) B-cells was a statistically significant negative predictor of response, both regarding DCR (OR=0.05, 95%CI=0.00-0.67, p=0.024) and ORR (OR=0.09, 95%CI=0.01-0.96, p=0.046). An increase of the frequency of switched memory B-cells was significantly associated with reduced odds for DCR (OR=0.06, 95%CI=0.01-0.70, p=0.025). Patients with an increased frequency of naïve B-cells were more likely to benefit from ICI therapy as indicated by an improved DCR (OR=12.31, 95%CI=1.13-134.22, p=0.039). CONCLUSION: In this study, certain B-cell subpopulations were associated with ICI treatment response in various human cancer types

Transurethrale Holmiumlaser Enukleation der Prostata (HoLEP) versus Transurethrale Elektroresektion der Prostata (TURP)

Ziele: Trotz ihrer signifikanten Morbidität stellt die transurethrale Resektion der Prostata (TURP) den gold standard dar für die instrumentelle Therapie der durch die benigne Prostatahyperplasie (BPH) bedingten Blasenauslassobstruktion. Mit dem Hochleistungs-Holmium: YAG Laser kann endoskopisch, in einer relativ blutungsarmen Weise, Prostatagewebe enukleiert werden. Wir verglichen die Technik der transurethralen Holmium-Laser-Enukleation der Prostata (HoLEP) mit der Standard-TURP bei der operativen Therapie von Prostataadenomen. Wir präsentieren die perioperativen Daten, die Kurz- und Langzeitergebnisse dieser randomisierten klinischen Studie. Material und Methoden: Insgesamt wurden 200 Patienten mit einer urodynamisch nachgewiesenen benignen Prostataobstruktion bei einem Prostatavolumen kleiner 100g im transrektalen Ultraschall in ein TURP- und HoLEP-Kollektiv randomisiert. Alle Patienten wurden präoperativ und postoperativ nach 1,6, 12, 18, 24 und 36 Monaten durch Erhebung des American Urological Association symptom score und Messung der maximalen Harnflussrate und des Restharns evaluiert. Die perioperativen Daten und die postoperativen Ergebnisse wurden verglichen. Alle Komplikationen wurden vermerkt. Ergebnisse: Bei der HoLEP waren die Katheterzeit, der Krankenhausaufenthalt und der Hämoglobinverlust signifikant geringer, jedoch die Operationszeit signifikant länger als bei der TURP. HoLEP und TURP führten zu signifikanter und anhaltender Verbesserung aller Miktionsparameter, wobei der Restharn bis einschließlich 36 Monate postoperativ in der HoLEP Gruppe signifikant geringer blieb. Auch die perioperative Morbidität war bei der HoLEP kleiner; Kontinenz, Potenz und Spätkomplikation waren in beiden Gruppen ähnlich. Schlussfolgerungen: HoLEP ist mindestens genauso effektiv wie TURP. HoLEP dauert länger, jedoch sind die perioperative Morbidität, Katheter- und Krankenhausdauer geringer. Beide Methoden zeigen befriedigende Langzeitergebnisse mit wenigen Spätkomplikationen. Dies bestätigt die Dauerhaftigkeit des Therapieerfolges dieser 2. Verfahren.Purpose: Transurethral electrocautery resection (TURP) is generally regarded as the gold standard surgical treatment for bladder outflow obstruction due to benign prostatic hyperplasia (BPH) despite its rather high morbidity. The high powered holmium: YAG laser can be used endoscopically to enucleate prostatic tissue in a relatively bloodless manner. The technique of transurethral holmium laser enucleation of the prostate (HoLEP) was compared to standard TURP for the surgical management of prostate adenomas. We present the perioperative data, short and long-term results of this randomized clinical trial. Materials and Methods: A total of 200 patients with urodynamic obstruction with a prostate less than 100 gm on transrectal ultrasound were randomized into 2 comparable groups and assigned to HoLEP or TURP. All patients were assessed preoperatively and followed prospectively 1, 6, 12, 18, 24, and 36 months postoperatively with an American Urological Association symptom score, peak urinary flow rate and post-void residual measurement. Perioperative data and postoperative outcome were compared. All complications were noted. Results: HoLEP was significantly superior to TURP in terms of catheter time, hospital stay and hemoglobin loss but operative time was significantly longer. HoLEP and TURP resulted in a significant and lasting improvement of all parameters with post-void residual volume still significantly better in the HoLEP group at the 36-month assessment. Perioperative morbidity was less in the HoLEP group; continence, potency and late complications were similar in both groups. Conclusion: HoLEP is at least as effective as TURP. HoLEP takes longer than TURP, but perioperative morbidtity, catheter time and hospital stay is less. Both treatments have satisfactory long term results with a low late complication rate. This confirms the durability of these 2 procedures

Management of Anterior Urethral Strictures in Adults: A Survey of Contemporary Practice in Germany

Introduction: Treatment methods of anterior urethral strictures in adults have undergone considerable changes in the recent past. Our goal was to determine national practice patterns among German urologists and to compare results with the results of prior international surveys. Methods: We conducted a survey on the management of urethral strictures among German urologists. Results: Eight hundred forty-five urologists, representing about 14.6% of German urologists, answered the survey. Most common procedures were direct vision internal urethrotomy (DVIU; 87.2%), blind internal urethrotomy (57.5%), dilatation (56.3%), ventral buccal mucosa graft urethroplasty (31.6%) and excision and primary anastomosis (28.9%). In case of a 3.5-cm bulbar stricture and in the case of a 1-cm bulbar stricture after 2 failed DVIUs, a consecutive urethroplasty was significantly more often favoured compared to transurethral treatment options (44.9 vs. 21.3% and 59.4 vs. 8.3%, both p < 0.001). Conclusion: Open urethral reconstruction reveals to be a more common method in practice nowadays. Adherence to recommended treatment algorithms improved in comparison to prior surveys

Management of Anterior Urethral Strictures in Adults: A Survey of Contemporary Practice in Germany

Introduction: Treatment methods of anterior urethral strictures in adults have undergone considerable changes in the recent past. Our goal was to determine national practice patterns among German urologists and to compare results with the results of prior international surveys. Methods: We conducted a survey on the management of urethral strictures among German urologists. Results: Eight hundred forty-five urologists, representing about 14.6% of German urologists, answered the survey. Most common procedures were direct vision internal urethrotomy (DVIU; 87.2%), blind internal urethrotomy (57.5%), dilatation (56.3%), ventral buccal mucosa graft urethroplasty (31.6%) and excision and primary anastomosis (28.9%). In case of a 3.5-cm bulbar stricture and in the case of a 1-cm bulbar stricture after 2 failed DVIUs, a consecutive urethroplasty was significantly more often favoured compared to transurethral treatment options (44.9 vs. 21.3% and 59.4 vs. 8.3%, both p < 0.001). Conclusion: Open urethral reconstruction reveals to be a more common method in practice nowadays. Adherence to recommended treatment algorithms improved in comparison to prior surveys

Tumor volume improves the long-term prediction of biochemical recurrence-free survival after radical prostatectomy for localized prostate cancer with positive surgical margins.

PURPOSE: To develop a novel application evaluating the effect of tumor volume (TV) and percentage of high-grade tumor volume (%HGTV) on long-term biochemical recurrence-free survival rate (BCRFS) after radical prostatectomy (RP) in patients with pT2 PCa. METHODS: Retrospective analysis of 903 men with pT2 PCa between 1992 and 2004 at a single European tertiary care center was performed. Cox regression models identified risk factors for BCR. A nomogram was developed to predict the BCRFS at 5, 10 and 15 years after RP. Decision curve analyses were performed to identify the net increase in cases identified by the full model. RESULTS: BCR-free survival rates at 5, 10 and 15 years were 94, 90 and 86 %. In Cox regression analyses, TV, %HGTV and positive surgical margin status (SM) were independent predictors of BCR. Predictive accuracies (PA) at 5, 10 and 15 years of the base model (PSA, Gleason score, SM) were 76.8 % (95 % CI 67.9-78.2 %), 70.5 % (95 % CI 64.9-75.0 %) and 68.1 % (95 % CI 60.6-73.5 %). The full model, including TV and %HGTV, achieved 76.9, 72.4 and 70.7 %. These PA differences were statistically significant at 10 and 15 years (p \u3c 0.001). CONCLUSIONS: TV and %HGTV could potentially serve as valuable measures to stratify patients at high risk of BCR. The use of our nomogram should be considered to counsel patients with pT2 disease and SM and to design appropriate follow-up or treatment regimens

Improved overall survival of metastatic renal cell carcinoma patients in the era of modern tyrosine kinase inhibitors and immune checkpoint inhibitors: results from a real-life, population-based Austrian study comprising three decades of follow-up

BACKGROUND: The treatment landscape of metastatic renal cell carcinoma (mRCC) has substantially advanced over the last three decades, whereby data from controlled clinical trials indicate significant improvements regarding patients’ overall survival (OS) in highly selected patient cohorts. The aim of this study is to evaluate the impact of potentially game changing drugs on patients’ outcomes by comparing three different historical mRCC treatment eras. METHODS: In all, 914 mRCC patients who were diagnosed between July 1985 and September 2020 were included into this observational study and assigned to three different treatment eras [‘cytokine’, ‘first-generation tyrosine kinase inhibitors (TKIs)’, and ‘modern TKIs/immunotherapy’] based on the EMA approval dates of sunitinib (July 2006) and nivolumab (June 2015) in mRCC treatment. OS was considered the primary study endpoint. Kaplan–Meier analyses, log-rank tests, and uni- and multivariable Cox regression models were performed. RESULTS: OS was significantly longer in patients of the modern TKIs/immunotherapy era (median OS not reached) as compared to the cytokine (2.4 years) and first-generation TKIs era (1.7 years, all p < 0.001). Moreover, patients of the modern TKIs/immunotherapy era demonstrated a significantly better prognosis [hazard ratio (HR): 0.41, 95% confidence interval (CI): 0.32–0.55, p < 0.001] compared to those of the cytokine era, while no statistically significant difference was observed between the cytokine and the first-generation TKIs era cohort (HR: 1.12, 95% CI: 0.89–1.41, p = 0.341). Subgroup analyses stratified by the International Metastatic RCC Database Consortium (IMDC) risk groups showed a significantly longer OS in the modern TKIs/immunotherapy era as compared to first-generation TKIs and cytokines across all IMDC risk groups. CONCLUSION: Significant advances in the systemic medical treatment of mRCC during the recent decade and the introduction of immunotherapy exerted a major impact on patient outcomes in terms of OS in a real-life population

Multiparametric MRI may help to identify patients with prostate cancer in a contemporary cohort of patients with clinical bladder outlet obstruction scheduled for holmium laser enucleation of the prostate (HoLEP)

Objective: To investigate the value of standard [digital rectal examination (DRE), PSA] and advanced (mpMRI, prostate biopsy) clinical evaluation for prostate cancer (PCa) detection in contemporary patients with clinical bladder outlet obstruction (BOO) scheduled for Holmium laser enucleation of the prostate (HoLEP). Material and Methods: We retrospectively analyzed 397 patients, who were referred to our tertiary care laser center for HoLEP due to BOO between 11/2017 and 07/2020. Of those, 83 (20.7%) underwent further advanced clinical PCa evaluation with mpMRI and/or prostate biopsy due to elevated PSA and/or lowered PSA ratio and/or suspicious DRE. Logistic regression and binary regression tree models were applied to identify PCa in BOO patients. Results: An mpMRI was conducted in 56 (66%) of 83 patients and revealed PIRADS 4/5 lesions in 14 (25%) patients. Subsequently, a combined systematic randomized and MRI-fusion biopsy was performed in 19 (23%) patients and revealed in PCa detection in four patients (5%). A randomized prostate biopsy was performed in 31 (37%) patients and revealed in PCa detection in three patients (4%). All seven patients (9%) with PCa detection underwent radical prostatectomy with 29% exhibiting non-organ confined disease. Incidental PCa after HoLEP (n = 76) was found in nine patients (12%) with advanced clinical PCa evaluation preoperatively. In univariable logistic regression analyses, PSA, fPSA ratio, and PSA density failed to identify patients with PCa detection. Conversely, patients with a lower International Prostate Symptom Score (IPSS) and PIRADs 4/5 lesion in mpMRI were at higher risk for PCa detection. In multivariable adjusted analyses, PIRADS 4/5 lesions were confirmed as an independent risk factor (OR 9.91, p = 0.04), while IPSS did not reach significance (p = 0.052). Conclusion: In advanced clinical PCa evaluation mpMRI should be considered in patients with elevated total PSA or low fPSA ratio scheduled for BOO treatment with HoLEP. Patients with low IPSS or PIRADS 4/5 lesions in mpMRI are at highest risk for PCa detection. In patients with a history of two or more sets of negative prostate biopsies, advanced clinical PCa evaluation might be omitted