Biology of BCG response in non-muscle invasive bladder cancer - 2021 IBCN Updates Part III.

Bacillus Calmette-Guerin (BCG) remains the only FDA-approved first-line therapy in patients with high-risk non-muscle invasive bladder cancer. Recurrences, even after adequate BCG therapy, are common and the efficacy of second-line therapies remains modest. Therefore, early identification of patients likely to recur and treatment after recurrence remain critical unmet needs in the clinical care of bladder cancer patients. To address these deficits, a better understanding of the mechanisms of resistance to BCG-therapy is needed. The virtual update of the International Bladder Cancer Network (IBCN) on the biology of response to BCG focused on potential mechanisms and markers of resistance to intravesical BCG therapy. The insights from this meeting will be highlighted and put into context of previously reported mechanisms of resistance to BCG in this review.

Expression patterns of the immune checkpoint ligand CD276 in urothelial carcinoma.

BACKGROUND: CD276 is an immune checkpoint molecule. Elevated CD276 expression by urothelial carcinoma is associated with poor prognosis, but little is known about its expression across different tumor stages. We therefore investigated CD276 expression in bladder cancer (BC) cells and in tissue samples of BC stages from pT2 to pT4. METHODS: CD276 expression was explored in 4 urothelial cancer cell lines and 4 primary normal urothelial cell populations by quantitative RT-PCR, Western blot and flow cytometry. CD276 was investigated in bladder tumors from 98 patients by immunohistochemistry using a score (0-300) incorporating both, staining intensity and area of CD276 staining. Normal appearing urothelium in the bladder of the same patients served as controls. RESULTS: The urothelial carcinoma cell lines expressed significantly higher levels of CD276 on transcript (p < 0.006), total protein levels (p < 0.005), and on the cell surface (p < 0.02) when compared to normal urothelial cells. In pT2-T4 tumor tissue samples, CD276 was overexpressed (median score 185) when compared to corresponding healthy tissues from the same patients (median score 50; p < 0.001). No significant differences in CD276 expression were recorded in late, locally advanced ≥ pT3a tumors (median score 185) versus organ-confined < pT3a tumors (median score 190), but it was significantly lower in the normal urothelial tissue associated with ≥ pT3a tumors (median score 40) versus < pT3a tumors (median score 80; p < 0.05). CONCLUSION: CD276 expression is significantly elevated in urothelial carcinoma cells in all stages but varies between individuals considerably. Reduced CD276 expression in normal urothelial cells may imply that these cells would be protected from CD276-mediated immuno therapies.

[Immunotherapy in bladder cancer-quo vadis? Update on current trials and developments]. / Immunonkologische Therapie des Harnblasenkarzinoms ­ quo vadis? Update zu aktuellen Studien und weiteren Entwicklungen.

BACKGROUND: Great advances have been made for the treatment of urothelial carcinoma by the introduction of checkpoint inhibitors (CPI). Single-agent immunotherapy with CPIs has been approved for patients with metastatic or locally advanced inoperable urothelial carcinoma who have either progressed during or after platinum-based chemotherapy or who are cisplatin-ineligible. For cisplatin-ineligible patients, approval is restricted to patients with high programmed cell death ligand 1 (PD-L1) expression. For patients with nonmuscle invasive bladder cancer (NMIBC) or patients with muscle invasive bladder cancer (MIBC) who receive curative therapy, no CPIs have received approval in Germany. OBJECTIVES: To provide an overview of the current landscape of immunotherapy in patients with urothelial carcinoma. METHODS: Summary of the therapeutic landscape and resulting challenges based on currently published data using a PubMed search. RESULTS: In the treatment of metastatic or inoperable urothelial carcinoma, CPIs represent standard treatment. Depending on the results of currently performed trials, an extension of its use to the perioperative setting (neoadjuvant/adjuvant) and to patients with Bacillus Calmette Guérin (BCG) unresponsive NMIBC in the near future is currently being discussed. CONCLUSIONS: Immuno-oncologic treatment using CPIs has become an integral part of the management of patients with advanced bladder cancer. For biomarker-based patient selection and combination therapies, there is an urgent need for further investigations within clinical trial protocols.

[Mode of action, new targets and potential biomarkers in modern immunotherapy]. / Wirkmechanismen, neue Angriffspunkte und potentielle Biomarker bei moderner Immuntherapie.

Immune checkpoint inhibitors (ICI) have significantly improved the systemic therapy of metastatic disease in genitourinary malignancies. With the European Medicines Agency (EMA) approval of the antibodies nivolumab and pembrolizumab directed against programmed cell death 1 (PD-1) as well as the PD-L1 antibody atezolizumab, three agents are available for the treatment of metastatic urothelial carcinoma and renal cell carcinoma. This article describes the underlying mode of action of PD-1/PD-L1 blockade and other ICIs to activate the immune system for effective tumor rejection. Future therapeutic strategies are focusing on the combination of ICI with targeted therapies to enhance the immune defense, especially in the local tumor microenvironment. A further clinical need exists for the establishment of biomarkers to predict a therapy response under ICI, in particular for the role of the PD-L1 status. Biomarkers for predicting primary or acquired therapy resistance are also of clinical importance to enable good patient selection for ICI therapy.

No influence of smoking status on the performance of urine markers for the detection of bladder cancer.

PURPOSE: The performance of urinary markers for detecting bladder cancer (BC) is influenced by various factors. The aim of the present study was to evaluate the influence of smoking habits on the performance of four commonly used urine markers. METHODS: Urine samples of 723 patients with suspected BC were analysed using urine cytology, fluorescence in situ hybridization (FISH), immunocytology (uCyt+ test), and quantitative nuclear matrix protein 22 (NMP22) immunoassay. The smoking habits of all patients were recorded and a cystoscopy performed within 2 weeks after urinary marker testing. Rates of false negative and false positive results were compared between non-smokers, former smokers, and current smokers by contingency analyses. RESULTS: We included 723 patients in this study, 431 (59.6%) of which were non-smokers, 215 former smokers (29.7%), and 77 (10.7%) current smokers. 148 patients (20.5%) had a tumour at the time of urinary marker testing. Respective rates of false positive test results among non-smokers, former smokers, and current smokers were: 16.3, 19.1, and 11.5% (p = 0.81) for urine cytology; 36.8, 42.0, and 32.7% for the uCyt+ test (p = 0.88); 18.0, 19.1, and 13.5% for FISH (p = 0.66); and 69.5, 71.6, and 71.2% for NMP22 (p = 0.67). Respective rates of false negatives among non-smokers, former smokers, and current smokers were: 31.4, 15.1, and 28.0% for cytology (p = 0.34); 21.4, 22.6, and 16.0% for uCyt+ test (p = 0.67); 24.3, 13.2, and 28.0% for FISH (p = 0.88); and 10.0, 18.9, and 8.0% for NMP22 (p = 0.80). CONCLUSIONS: Our results strongly suggest that smoking habits do not affect performance characteristics of urinary markers in the diagnostics of BC.

[Current guideline-oriented follow-up of small renal masses : Applied risk scores and future outlook]. / Aktuelle leitliniengerechte Nachsorge kleiner Nierentumoren : Angewandte Risikoscores und Zukunftsausblick.

After surgical resection of renal cell carcinoma by laparoscopic or open partial or complete nephrectomy, medical aftercare based on the current guidelines should be provided. This seems desirable, especially because one third of patients after initial curative tumor resection develop recurrence over time. In this article, the current recommendations for follow-up will be systematically presented based on the accepted German S3 guideline and the European Association of Urology (EAU) guideline. Another point of this article will be the presentation of the currently applied risk scores to predict prognosis with a focus on molecular markers. The goal is to improve the prediction of survival and to facilitate risk-adjusted aftercare.

[TKI 2.0 - changes in the medical treatment of renal cell carcinoma]. / TKI 2.0 ­ Wandel in der medikamentösen Therapie des Nierenzellkarzinoms.

Only for renal cell carcinoma (RCC) in a local stage curative treatment option by surgical resection exists. For metastatic disease the 5­year survival rate decreases radically. A factor that contributes to this is the low sensibility to radiation and chemotherapeutics. Since the approval of the tyrosine kinase inhibitors in 2006 effective drugs for the treatment of mRCC is available. The specific inhibition of the vascular-endothelial-growth (VEGF)-receptor and the "mammalian Target of Rapamycin" (mTOR) leads to a prolongation of the progression-free survival as well as the overall survival rate. For a long time, the current target therapy with TKI appeared to be exhausted, but since recently research has gone a step further. Thus, Cabozantinib and Lenvatinib in the combination with Everolimus have been approved for second-line therapy in mRCC. For the first time a clinical study demonstrated positive results for an adjuvant treatment with sunitinib in patients with a high-risk RCC. Furthermore, in april 2016 the immune checkpoint inhibitor Nivolumab was approved for second-line therapy in mRCC in Germany. The following report examines briefly the current therapeutic recommendations, new findings and drug approvals and ongoing clinical trials.

Laparoscopic radical nephrectomy with inferior vena cava thrombectomy: highlight of key surgical steps.

OBJECTIVE: Vascular involvement in the form of renal vein (RV) or inferior vena cava (IVC) thrombus can be seen in 4-10% of patients presented with RCC. In patients without presence of metastasis, surgical treatment in the form of radical nephrectomy remains the treatment of choice with 5-year survival rates of 45-70%. Open surgery is still the first treatment option of choice at the moment for RCC patients with IVC thrombus. MATERIALS AND METHODS: In our study, we are reporting a case of patient with RCC and level I IVC thrombus treated with laparoscopy. Our patient is a 72 years old man with underlying co-morbidity of hypertension and chronic kidney disease (CKD) presented with right-sided RCC. The CT scan done showed a large right renal upper pole tumor measuring 8.4x5.2cm with level I IVC thrombus (Figure-1). There were no regional lymphadenopathy and the staging scans were negative. RESULTS: The operative time was 124 minutes and blood loss was minimal. The patient was progressed to diet on POD 1 with bowel movement on POD 2. There was no significant change in the pre and post-operative glomerular filtration rate (GFR). The surgical drain was removed on POD2. The patient was discharged well on POD 5. There were no perioperative complications. The pathology was pT3bN0M0 Fuhrman grade II clear cell RCC. CONCLUSIONS: As a conclusion, laparoscopic radical nephrectomy and IVC thrombectomy is a complex and technically demanding surgery. With advancement of surgical skills as well as technology, more cases of minimally invasive laparoscopic radical nephrectomy and IVC thrombectomy can performed to improve the perioperative outcomes of carefully selected patients in a high volume center.

Impact of perioperative chemotherapy on survival in patients with advanced primary urethral cancer: results of the international collaboration on primary urethral carcinoma.

BACKGROUND: To investigate the impact of perioperative chemo(radio)therapy in advanced primary urethral carcinoma (PUC). PATIENTS AND METHODS: A series of 124 patients (86 men, 38 women) were diagnosed with and underwent surgery for PUC in 10 referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank testing was used to investigate the impact of perioperative chemo(radio)therapy on overall survival (OS). The median follow-up was 21 months (mean: 32 months; interquartile range: 5-48). RESULTS: Neoadjuvant chemotherapy (NAC), neoadjuvant chemoradiotherapy (N-CRT) plus adjuvant chemotherapy (ACH), and ACH was delivered in 12 (31%), 6 (15%) and 21 (54%) of these patients, respectively. Receipt of NAC/N-CRT was associated with clinically node-positive disease (cN+; P = 0.033) and lower utilization of cystectomy at surgery (P = 0.015). The objective response rate to NAC and N-CRT was 25% and 33%, respectively. The 3-year OS for patients with objective response to neoadjuvant treatment (complete/partial response) was 100% and 58.3% for those with stable or progressive disease (P = 0.30). Of the 26 patients staged ≥cT3 and/or cN+ disease, 16 (62%) received perioperative chemo(radio)therapy and 10 upfront surgery without perioperative chemotherapy (38%). The 3-year OS for this locally advanced subset of patients (≥cT3 and/or cN+) who received NAC (N = 5), N-CRT (N = 3), surgery-only (N = 10) and surgery plus ACH (N = 8) was 100%, 100%, 50% and 20%, respectively (P = 0.016). Among these 26 patients, receipt of neoadjuvant treatment was significantly associated with improved 3-year relapse-free survival (RFS) (P = 0.022) and OS (P = 0.022). Proximal tumor location correlated with inferior 3-year RFS and OS (P = 0.056/0.005). CONCLUSION: In this series, patients who received NAC/N-CRT for cT3 and/or cN+ PUC appeared to demonstrate improved survival compared with those who underwent upfront surgery with or without ACH.

[Complex residual tumors after chemotherapy of nonseminomatous germ cell tumors. Laparoscopic management - limits and chances]. / Komplexe Residualtumoren nach Chemotherapie bei nichtseminomatösen Keimzelltumoren. Laparoskopisches Management - Grenzen und Chancen.

PURPOSE: Laparoscopic retroperitoneal lymph node dissection (L-RPLND) is often required in patients with metastatic nonseminomatous germ cell tumors (NSGCT) and residual tumors after chemotherapy. Laparoscopy has become established as a safe procedure in the surgical management of these tumors. Due to the rapid development of laparoscopy, complex retroperitoneal and even intrathoracic residuals can also be treated in high volume centers. PATIENTS AND METHODS: This study included 21 retrospectively identified NSGCT and seminoma patients (mean age 29 years) with metastatic disease and clinical stage (CS) IIA-IIIB. A bilateral L-RPLND was performed in all male patients between 2009 and 2014. In 19 patients an infiltration of the great vessels was detected during surgery and vascular reconstruction was necessary. In 2 patients an intrathoracic residual 5.4 cm and 7 cm in size, respectively, was diagnosed during follow-up. Exclusion criteria for L-RPLND were positive tumor markers after chemotherapy, patients with local recurrence after previous open L-RPLND and patients with excessive vascular involvement. RESULTS: In this series no conversions to open surgery were necessary. The mean tumor size post-chemotherapy was 3.6 cm (range 1.5-9.7 cm). The mean measured blood loss was 294 ml (range 50-1000 ml). The mean hospitalization time was 6 days (range 3-9 days) and mean follow-up was 16 months (range 1-37 months). No complications higher than grade II (Clavien-Dindo classification) were registered in the immediate postoperative course. During the follow-up period no in-field recurrences were registered. CONCLUSION: The L-RPLND seems to be a safe alternative surgical procedure for certain complex residuals with vascular involvement after chemotherapy of testicular cancer. Bilateral L-RPLND is technically feasible and reproducible under guaranteed oncological principles. An infiltration of the great vessels and also intrathoracic residuals can be managed in selected patients without compromising the clinical and oncological course.

[Laparoscopic partial nephrectomy for renal tumors. Time for a new standard?]. / Laparoskopische Nierenteilresektion bei Nierentumoren. Zeit für einen neuen Standard?

PURPOSE: Our aim was to evaluate the laparoscopic partial nephrectomies (LPN) performed at our hospital and compare the results with those from other current studies on partial nephrectomy. PATIENTS AND METHODS: Between March 2006 and January 2014, 280 patients were treated with LPN in our hospital. We evaluated age, sex, and surgical parameters like operating time, warm ischemia time (WIT), hospital stay, complications, tumor staging, grading, and size RESULTS: The patients were 61.6±12.4 years old. The median operating time for LPN was 134±51 min. A total of 30% of the operations were treated using the zero ischemia technique. The WIT was 19.9±9.8 min. The WIT of the last 50 LPN performed was 13±7 min. Complications were documented in 15% of the LPNs. CONCLUSION: LPN is a curative treatment option for the renal cell carcinoma similar to open partial nephrectomy; however, laparoscopy is associated with lower morbidity.

[Treatment of invasive bladder cancer: robot-assisted radical cystectomy and intracorporeal urinary diversion]. / Therapie des invasiven Harnblasenkarzinoms : Roboterassistierte radikale Zystektomie und intrakorporale Harnableitung.

PURPOSE: Robot-assisted radical cystectomy (RARC) and intracorporeal urinary diversion are only performed in a few centers of excellence worldwide. Functional and oncologic outcomes are comparable. We report on our experience with RARC and intracorporeal diversion. PATIENTS AND METHODS: We retrospectively identified 86 RARCs in 72 men and 14 women (mean age 69.7 years). All patients underwent robot-assisted radical cystectomy and pelvic lymphadenectomy followed by intracorporeal urinary diversion using ileal conduit or neobladder. Of the 86 patients, 24 patients (28%) underwent intracorporeal ileal conduit and 62 patients (72%) underwent intracorporeal neobladder formation. A Studer pouch was created in all who underwent intracorporeal neobladder diversion. Cancer specific survival (CSS) and overall survival (OS) are reported. RESULTS: The mean operative time was 418.9 min (range 205-690 min) and blood loss was 380 ml (range 100-1000 ml). The mean hospital stay was 17.5 days (range 5-62 days). All the surgeries were completed with no open conversions. Minor complications (grade I and II) were reported in 23 patients, while major complications (grade III and above) were reported in 21 patients. The mean nodal yield was 20.3 (range 0-46). Positive margins were found in in 8%. The average follow-up was 31.5 months (range 3-52 months). Continence could be achieved in 88% of patients who received an intracorporeal neobladder. The cancer-specific survival (CSS) and overall survival (OS) were 80% and 70%, respectively. CONCLUSION: RARC with intracorporeal diversion seems to be safe and reproducible in tertiary centers with robotic expertise. Operative times are acceptable and complications as well as functional and oncologic outcomes are comparable. Further standardization of RARC with intracorporeal diversion may lead to a wider adoption of the approach.

Cost effective laparoendoscopic single-site surgery with a reusable platform.

BACKGROUND AND OBJECTIVES: Many disposable platforms have been applied in laparoendoscopic single-site surgery (LESS). Besides technical issues, cost is one of the limiting factors for its widespread acceptance. The current study describes the first completely reusable LESS-platform. METHODS: We performed LESS-procedures in 52 patients including nephrectomy (18), adrenalectomy (2), partial nephrectomy (3), pyeloplasty (4), renal cyst ablation (4), pelvic lymphadenectomy (15), and lymphocele ablation (6). All procedures were conducted using a novel reusable single-port device (X-Cone, Karl-Storz) with a simplified set of instruments. We obtained perioperative and demographic data, including a visual analogue pain scale (VAS), and a complication reporting system based on Clavien grading. RESULTS: Mean age was 50.04 y. Conversion to standard laparoscopy was necessary in 3 cases and addition of a needlescopic instrument in 6 cases. There was no open conversion. Intra- and postoperative complications occurred in 3 (Clavien II in 2 and III in 1) cases. Mean operative time was 110, 90, and 89 min, and hospital stay was 4.9, 3.1, and 3.6 d for nephrectomy, pelvic lymphadenectomy, and pyeloplasty, respectively. Mean VAS was 2.13, 1.07, and 1.5 while blood loss was 81.3 mL, 25.67 mL, and 17.5 mL, respectively. Mean lymph node yield was 15 (range, 8 to 21). CONCLUSIONS: A completely reusable LESS-platform is applicable to various uses in urology, yielding favorable functional and cosmetic results. Reusable materials are useful to reduce the cost of LESS, further increasing its acceptance. LESS with a completely reusable platform is more cost effective than standard laparoscopy.

Influence of body mass index, surgical approach and lymphadenectomy on the development of symptomatic lymphoceles after radical prostatectomy.

PURPOSE: Identification of factors influencing lymphocele formation requiring intervention after radical prostatectomy. METHODS: 302 patients undergoing radical retropubic prostatectomy (RRP, n = 174) or transperitoneal robot-assisted laparoscopic prostatectomy (RALP, n = 128) by the same surgeon were retrospectively reviewed. Incidence of symptomatic lymphoceles (SLC) was compared with clinical and pathological data (contingency analyses, Wilcoxon-Kruskal-Wallis test). RESULTS: Sixteen patients (5.3%) developed SLC. SLC occurred significantly more frequently after RRP compared to RALP (8.0 vs. 0.8%, p = 0.0008). Patients with SLC had more lymph nodes (LN) removed median (17 vs. 13, p = 0.009) and a significantly lower BMI (median 24.4 vs. 26.4, p = 0.0008). Presence of LN metastases (n = 18 patients, 6.0%) showed no statistical impact on SLC. In a multivariate analysis surgical method, the number of resected LN and the BMI remained independent predictors of SLC formation. CONCLUSIONS: The lower incidence of SLC after RALP compared to RRP probably results from peritoneal drainage of lymphatic fluid. The correlation of removed LN and SLC might be explained by increased injury of lymphatic vessels during more extended LN dissection. Why patients with lower BMI are more prone to develop SLC still remains unclear. However, early postoperative mobilization in nonobese patients might be a contributing factor.

[Post-chemotherapy laparoscopic retroperitoneal lymph node dissection in low volume residual germ cell cancer: a technique to reduce morbidity]. / Laparoskopisch retroperitoneale Lymphadenektomie bei Low-volume-Keimzelltumoren nach Chemotherapie : Ein Verfahren zur Verringerung der Morbidität.

PURPOSE: Retroperitoneal lymph node dissection (RPLND) is the most appropriate method for the detection of residual tumor tissue and mature teratoma after chemotherapy in patients with advanced nonseminomatous (NSGCT) or seminomatous (SGCT) germ cell tumors in clinical stage II-III. Open surgical procedures are associated with higher morbidity rates and laparoscopic RPLND offers a minimally invasive procedure with equivalent oncological safety and low morbidity. METHODS: In 39 patients laparoscopic RPLND (L-RPLND) after platinum-based chemotherapy for clinical stage IIa-III NSGCT was performed unilaterally as well as bilaterally by two surgeons. Patients with retroperitoneal residual tumor >1 cm and normalization of tumor markers after chemotherapy were included. Bilateral L-RPLND was performed with complete contralateral nerve sparing while the decision for ipsilateral nerve preservation was based on the volume of the residual mass in the respective standard field. RESULTS: The L-RPLND was completed in all patients without conversion. Median operation time was 248 min (range 95-397 min) and mean hospitalization time was 5 days (range 3-14 days). Furthermore, there was no difference in recurrence rate of the disease (p=0.45) between patients with unilateral or bilateral dissection. The postoperative ejaculatory function was normal in 37 out of 39 patients. The median follow-up period was 18.5 months (range 3-38 months) and 3 out of 39 patients developed recurrence (7.69 %). CONCLUSIONS: Post-chemotherapy L-RPLND is feasible with a lower complication rate and an adequate oncological safety and functional outcome. Due to the complexity of L-RPLND the procedure remains limited to institutions with extensive laparoscopic experience.

[Primary monosymptomatic enuresis: diagnostics and therapy]. / Primäre Monosymptomatische Enuresis: Diagnostik und Therapie.

Nocturnal enuresis is one of the most common problems in childhood. In this article a standardized terminology for basic diagnostics additionally to extended diagnostics will be presented. Depending on the findings a specialized therapy can be performed. Besides drug therapy with antidiuretic hormone (ADH) sleep arousal devices can be used and the combination of both approaches also shows excellent results. At the end of therapy a protracted withdrawal shows better results than abrupt cessation.

[Laparoendoscopic single-site surgery in urology using reusable systems]. / Laparoendoskopische Single-site-Chirurgie in der Urologie durch Einsatz eines wieder verwendbaren Systems.

PURPOSE: Many disposable platforms have been available for laparoendoscopic single-site surgery (LESS) for a long time. Besides technical challenges cost remains the limiting factor for the widespread use of LESS. We present our experiences with the first completely reusable LESS platform. METHODS: We performed LESS procedures in 52 patients, including nephrectomy (n=18), adrenalectomy (2), partial nephrectomy (3), pyeloplasty (4), renal cyst ablation (4), pelvic lymphadenectomy (15) and lymphocele ablation (6). All procedures were carried out using a novel reusable single-port device (X-ConeR, Karl-Storz) with a simplified combination of standard and preformed instruments. Perioperative and demographic data including a visual analogue pain scale (VAS) were obtained. Complications were recorded using the Clavien classification. RESULTS: The mean age of the patients was 50.04 years. Conversion to standard laparoscopy was necessary in 3 cases and the additional use of a 3 mm needle instrument in 6 cases. There were no open conversions. Intraoperative and postoperative complications occurred in 3 (Clavien II in 2 and III in 1) cases. Mean operating time was 110, 90, and 89 min and hospital stay was 4.9, 3.1 and 3.6 days for nephrectomy, pelvic lymphadenectomy, and pyeloplasty, respectively. The mean VAS was 2.13, 1.07 and 1.5 while blood loss was 81.3 ml, 25.67 ml and 17.5 ml, respectively. CONCLUSIONS: The LESS technique with a completely reusable platform is applicable to various indications in urology yielding favorable functional and cosmetic results. This novel simplified combination of instruments facilitates handling and shortens the learning curve. Reusable materials may help to reduce cost leading to a wider acceptance of LESS.

Influence of age on false positive rates of urine-based tumor markers.

INTRODUCTION: Several influencing factors on false positive rates (FPRs) of urine-based tumor markers in the detection of urothelial cancer (UC) have been identified. We evaluated age as a possible influencing factor. METHODS: Urinary cytology (Cyt), UroVysion (FISH), ImmunoCyt (uCyt+) and NMP22 were determined in 1,554 patients suspicious for UC of the bladder before cystoscopy and in case of cancer detection before TURB. Additionally, upper urinary tract imaging was performed. Maker sensitivity, specificity and FPRs were evaluated in the entire cohort and in subgroups divided by age into <50, ≥ 50-70 and ≥ 70 years. Contingency tables and the Cochrane Armitage tests were used for statistical comparisons. RESULTS: UC was found in 377 and no UC in 1,177 (75 %) patients. A total of 336 patients were diagnosed with UC of the bladder and 41 with UC of the upper urinary tract. Overall sensitivity and specificity for Cyt were 82 and 82 %: for FISH, 73 and 79 % and for uCyt+, 79 and 75 %, respectively. For NMP22, regardless of the exclusion criteria they were 72 and 34 % and after exclusion of urinary tract infection (UTI) or prior to manipulation 46 and 86 %, respectively. Significantly higher FPRs were found with increasing age for Cyt (p = 0.001), a trend to higher FPRs for uCyt+ (p = 0.11) and almost no difference for FISH (p = 0.63). For NMP22, differences became significant after exclusion of patients with UTI or prior manipulation (p = 0.02). CONCLUSIONS: The results of the present study give evidence that false positive rates of Cyt and NMP22 increase with age indicating that age should be respected for their correct interpretation.

[Primary treatment for localized prostate cancer: evaluation of patients' quality of life]. / Patienten nach Primärtherapie eines klinisch lokal begrenzten Prostatakarzinoms: Evaluation der Lebensqualität.

BACKGROUND: Radical prostatectomy (RP) and percutaneous radiotherapy (RT) are viable options for the primary treatment of localized prostate cancer (PC). Given the comparable efficacy of both modalities quality of life (QOL) has been suggested as an additional decision criterion. In recent years several validated instruments have been introduced to assess QOL. Most of them allow for patient-based rating of QOL. AIM: Herein, we aim to compare QOL after RP and RT in our own cohort of patients in Tübingen using validated questionnaires. METHODS: In total, 165 patients who had been treated for PC in Tübingen were enrolled. Of those 100 men had RP and 65 had RT. The validated QOL questionnaires EORTC QLQ-C30 and EORTC QLQ-PR 25 were used for assessment. Statistical analyses focused on analyses of variance. RESULTS: Concordant to previous studies it could be shown that RP mainly creates voiding problems most importantly urinary incontinence but also erectile dysfunction. After RT, patients mainly complained about disturbed bowel function including diarrhea and proctitis as well as about urgency and frequency. RP patients had better PF2 Scale values than RT patients (p= 0.00357143). On DI scales RT patients yielded significantly poorer values than the RP group (p= 0.003333). CONCLUSION: Our data comply well with those from other international centers. QOL is an important yet underestimated variable in oncological research. Our investigations underline the importance of an interdisciplinary approach for the successful management of PC.

[Treatment of metastatic bone disease and treatment-induced osteoporosis in prostate cancer. Evolution of osteoprotective strategies]. / Behandlung von ossären Metastasen und therapieinduzierter Osteoporose beim Prostatakarzinom. Evolution osteoprotektiver Strategien.

Patients with prostate cancer and bone metastases on average experience one skeletal-related event per year. To avoid complications caused by bone metastases and androgen deprivation therapy-induced osteoporosis, which lead to significant increases in costs and mortality, bone metabolism can be influenced in several ways. Bisphosphonates, which directly inhibit signalling pathways in osteoclasts, can reduce the rate of skeletal-related events in metastatic prostate cancer. The RANKL antibody denosumab inhibits the crosstalk between osteoblasts, osteoclasts and tumour cells and has been shown to reduce the rate of vertebral fractures in patients with treatment-induced osteoporosis. Furthermore, it has been recently shown to prevent skeletal-related events in prostate cancer patients with metastatic bone disease. In patients with castration resistant prostate cancer, denosumab prolongs bone-metastasis-free-survival. Whereas ample data are available about side effects of bisphosphonates, limited evidence exists about the long-term safety profile of denosumab. Therefore, a thorough patient selection is advocated for therapeutic application of denosumab in patients with prostate cancer.