Adjuvant vs. progression-triggered treatment with gemcitabine in platinum-ineligible high-risk bladder cancer patients: Long-term follow-up of a randomized phase 3 trial.

BACKGROUND: Cisplatin-based chemotherapy (ChT) is the preferred perioperative treatment in muscle-invasive urothelial carcinoma of the urinary bladder (UCUB). Nevertheless, a certain number of patients are ineligible for platinum-based ChT. This trial compared immediate adjuvant vs. delayed gemcitabine ChT at progression in platinum-ineligible patients with high-risk UCUB. METHODS: High-risk platinum-ineligible UCUB patients (n = 115) were randomized 1:1 to adjuvant gemcitabine (n = 59) or gemcitabine at progression (n = 56). Overall survival was analyzed. Additionally, we analyzed progression-free survival (PFS), toxicity and quality of life (QoL). RESULTS: After a median follow-up of 3.0 years (inter quartile range [IQR]: 1.3-11.6), adjuvant ChT did not significantly prolong overall survival (OS) (HR: 0.84; 95% CI: 0.57-1.24; P = 0.375), with 5-year OS of 44.1% (95% CI: 31.2-56.2) and 30.4% (95% CI: 19.0-42.5), respectively. We noted no significant difference in PFS (HR: 0.76; 95% CI: 0.49-1.18; P = 0.218), with 5-year PFS of 36.2% (95% CI: 22.8-49.7) in the adjuvant group and 22.2% (95% CI: 11.5%-35.1%) when treated at progression. Patients with adjuvant treatment showed a significantly worse QoL. The trial was prematurely closed after recruitment of 115 of the planned 178 patients. CONCLUSIONS: There was no statistically significant difference in terms of OS and PFS for patients with platinum-ineligible high-risk UCUB receiving adjuvant gemcitabine compared to patients treated at progression. These findings underline the importance of implementing and developing new perioperative treatments for platinum-ineligible UCUB patients.

The Overall Survival Benefit for Patients with T1 Renal Cell Carcinoma after Nephron-Sparing Surgery Depends on Gender and Age.

Due to the recommendations in the urological guidelines to perform nephron-sparing surgery in patients with organ-confined renal cell carcinoma (RCC), the customary therapy regimen changed, but it is not well studied yet whether partial nephrectomy (PN) especially in the elderly is beneficial. From 2000 to 2015, 3,592 patients from 7 clinics undergoing surgery in RCC were identified; 2,323 had T1 tumours. We retrospectively compared the overall survival benefit of patients with T1 RCC who underwent either PN or radical nephrectomy (RN) and studied effects of age and gender. RESULTS: In T1 RCC, PN was beneficial in male patients (p = 0.0006) independent of age, especially in those men ≤75 years of age (p = 0.0005); but PN was not beneficial for female patients (p = 0.0629) regardless of age and male patients older than 75 years (p = 0.736). The OS of female patients after RN and male patients after PN is the same, regardless of age. A life expectancy of more than 45 months at least is necessary to experience an overall survival benefit after PN. CONCLUSIONS: There should be harder proven indications for PN in female patients and especially in all patients older than 75 years, particularly with regard to perioperative risk factors.

Everolimus in metastatic renal cell carcinoma after failure of initial vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFr-TKI) therapy: results of an interim analysis of a non-interventional study.

BACKGROUND: Everolimus is approved for treatment of anti-vascular endothelial growth factor (VEGF)-refractory patients with metastatic renal cell carcinoma (mRCC). Clinical trials rarely mirror treatment reality. Thus, a broader evaluation of everolimus is valuable for routine use. PATIENTS AND METHODS: A German multicenter non-interventional study documented mRCC patients starting everolimus after failure of initial VEGF-targeted therapy. Primary endpoint was effectiveness, defined as time to progression (TTP) according to investigator assessment (time from first dose to progression). RESULTS: Of 382 documented patients, 196 were included in this interim analysis. In the efficacy population (n = 165), median TTP was 7.0 months (95% confidence interval (CI) 5.1-9.0). Among patients with < or ≥ 6 months of previous VEGF-targeted therapy, median TTP was 6.6 months (95% CI 3.8-not estimable) and 7.4 months (95% CI 4.6-9.6), respectively. Most common adverse events were anemia (13%) and dyspnea (14%). Physicians assessed high tolerance and documented high adherence to everolimus therapy (approximately 97%). CONCLUSION: In routine clinical practice, everolimus is effective, as measured by median TTP (longer than median progression-free survival in RECORD-1 trial), and well tolerated. Our results support everolimus use in anti-VEGF-refractory patients with mRCC.

Intestinal oxalate absorption in patients with continent urinary diversion.

The objective of the study is to evaluate the post-operative effect of an orthotopic ileal neobladder or a Mainz pouch I bladder replacement on the extent of intestinal oxalate absorption. Gastrointestinal oxalate absorption was measured in six patients with an orthotopic ileal neobladder and in six patients with a Mainz pouch I bladder replacement. The function test applied was the [13C2]oxalate absorption test. With a range of 5.1-12.4%, the oxalate absorption of these patients was well within the reference range for healthy volunteers. The results from our small study indicate that such continent urinary diversions present no hazard for oxalate hyperabsorption and subsequent calcium oxalate urolithiasis.

CDC91L1 (PIG-U) is a newly discovered oncogene in human bladder cancer.

Genomic amplification at 20q11-13 is a common event in human cancers. We isolated a germline translocation breakpoint at 20q11 from a bladder cancer patient. We identified CDC91L1, the gene encoding CDC91L1 (also called phosphatidylinositol glycan class U (PIG-U), a transamidase complex unit in the glycosylphosphatidylinositol (GPI) anchoring pathway), as the only gene whose expression was affected by the translocation. CDC91L1 was amplified and overexpressed in about one-third of bladder cancer cell lines and primary tumors, as well as in oncogenic uroepithelial cells transformed with human papillomavirus (HPV) E7. Forced overexpression of CDC91L1 malignantly transformed NIH3T3 cells in vitro and in vivo. Overexpression of CDC91L1 also resulted in upregulation of the urokinase receptor (uPAR), a GPI-anchored protein, and in turn increased STAT-3 phosphorylation in bladder cancer cells. Our findings suggest that CDC91L1 is an oncogene in bladder cancer, and implicate the GPI anchoring system as a potential oncogenic pathway and therapeutic target in human cancers.

Treatment of penile strangulation caused by constricting devices.

Constricting devices placed on the penis present a challenge to urologists. Various nonmetallic and metallic objects are placed on the penis to increase sexual performance or because of autoerotic intentions. We describe five different cases of strangulating objects (wedding ring, metal plumbing cuff, bull ring, hammer- head, and plastic bottle neck) and demonstrate that each case needs individual handling in removing the object. The treatment of penile strangulation is decompression of the constricted penis to facilitate free blood flow and micturition. It requires no particular skill but does require resourcefulness to perform the removal simply and effectively, and with as little discomfort for the patient as possible.