Nocturia and associated mortality: observational data from the REDUCE trial

Importance: Nocturia (voids arising from sleep) is a ubiquitous phenomenon reflecting many diverse conditions, but whether it has significance in its own right remains uncertain. Objective: To determine whether nocturia is an independent risk factor for mortality Design: Observational study Setting: Global study with most sites in North America and Europe Participants: 7,343 men, ages 50-75 at Baseline from the REDUCE (Reduction by Dutasteride of Prostate Cancer Events) trial Exposures: Nocturia Main Outcome and Measures: Cox proportional hazards models were used to test the association between nocturia (voiding 3 more times per night) and all-cause mortality. Potential confounding variables included: age, race, region of origin, treatment group, self-reported coronary artery disease, diabetes mellitus, hypertension, and peripheral vascular disease, smoking, alcohol use, prostate volume, and diuretics. Self-reported sleep quality, as measured with the Medical Outcomes Study sleep scale, was entered as a final step in the model. Results: Nocturia was associated with increased risk for mortality (Hazard Ratio [HR] = 1.72; 95% CI 1.15-2.55) independent from all demographics and medical comorbidities. Inclusion of disturbed sleep in the model reduced the magnitude of the association (HR = 1.43; 95% CI 0.93-2.19). Conclusions and Relevance: The interruption of sleep by nocturia may have long-term impact on health and may warrant targeted intervention

Both acute and chronic inflammation are associated with lower perineural invasion in men with prostate cancer on repeat biopsy

Objectives: To evaluate the association between acute and chronic inflammation with the presence of perineural invasion (PNI) in prostate biopsies positive for prostate cancer (PCa). Material and methods: Retrospective analysis of 1399 prostate biopsies positive for PCa in the Reduction by Dutasteride of PCa Events (REDUCE) study. PCa, acute and chronic prostate inflammation, and PNI were assessed by central pathology review. The association between acute and chronic inflammations with PNI was evaluated using chi-square test and Kruskal-Wallis tests, and logistic regression adjusting for clinicopathological and biochemical variables. Results: PNI was identified in 133 (9.5%) biopsies. 267 (19.1%) biopsies had acute inflammation, 1038 (74.2%) had chronic inflammation, and 255 (18.2%) had both. The presence of acute and chronic inflammations was associated with each other (P<0.001). Chronic inflammation was associated with lower Gleason score (P=0.009) and lower tumor volume (P<0.001), while acute inflammation was associated with lower Gleason score (P=0.04), lower tumor volume (P=0.004) and higher prostate-specific antigen levels (P=0.05). In both uni- and multivariable analyses, chronic prostate inflammation was significantly associated with less PNI (univariable OR=0.54; 95% CI=0.37-0.79; P=0.001; multivariable OR=0.65; 95% CI=0.43-0.99; P=0.045). Acute prostate inflammation was associated with less PNI only in univariable analysis (univariable OR=0.51; 95% CI=0.29-0.89, P=0.018; multivariable OR=0.63; 95% CI=0.35-1.13; P=0.12). Conclusion: Acute and chronic prostate inflammation were both associated with a lower prevalence of PNI in prostate biopsies positive for PCa. If confirmed, this suggests that inflammation and immunomodulation can serve as areas of potential therapeutic design to mitigate PNI in PCa patients

Renal Cell Carcinoma with Isolated Lymph Node Involvement: Long-term Natural History and Predictors of Oncologic Outcomes Following Surgical Resection

Background: Renal cell carcinoma (RCC) with isolated lymph node (LN) involvement has historically been associated with poor prognosis. However, a subset of patients may experience long-term survival. Objective: To examine the natural history of RCC with isolated LN involvement following surgical resection with long-term follow-up, and to evaluate clinicopathologic features associated with disease progression and survival. Design, setting, and participants: A total of 138 patients with isolated pN1M0 RCC underwent partial or radical nephrectomy and LN dissection from 1980 to 2010. Intervention: Partial or radical nephrectomy with LN dissection. Outcome measurements and statistical analysis: Metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) were estimated using the Kaplan-Meier method. Associations between clinicopathologic features and oncologic outcomes were evaluated using Cox regression models. Results and limitations: Median follow-up among survivors was 8.5 yr. The 5-yr and 10yr MFS, CSS, and OS rates were 16% and 15%, 26% and 21%, and 25% and 15%, respectively. The median time to development of metastases was only 4.2 mo. On multivariable analysis, symptoms at presentation (hazard ratio [HR] 2.40; p = 0.03), inferior vena cava tumor thrombus (HR 1.99; p = 0.003), clear cell (HR 2.21; p = 0.01) and collecting duct/not otherwise specified (HR 4.28; p < 0.001) histologic subtypes, pT4 stage (HR 2.64; p = 0.005), and coagulative tumor necrosis (HR 2.51; p < 0.001) were independently associated with development of metastases. MFS rates at 1 yr after surgery were 71%, 63%, 33%, and 7% for patients with one, two, three, and four to five adverse features, respectively. Limitations include surgical selection bias. Conclusions: Although isolated pN1 disease portends a poor prognosis, a small subset of patients experience durable long-term survival after surgical resection of isolated lymphatic metastases. Adverse prognostic features may enhance patient risk stratification and facilitate multimodal management approaches. Patient summary: Although isolated lymph node metastases portend a poor prognosis, a small subset of patients experience long-term survival following surgical resection. (C) 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved