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Concept: Urology

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Background The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen (PSA) testing remains uncertain. Methods We compared active monitoring, radical prostatectomy, and external-beam radiotherapy for the treatment of clinically localized prostate cancer. Between 1999 and 2009, a total of 82,429 men 50 to 69 years of age received a PSA test; 2664 received a diagnosis of localized prostate cancer, and 1643 agreed to undergo randomization to active monitoring (545 men), surgery (553), or radiotherapy (545). The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up. Secondary outcomes included the rates of disease progression, metastases, and all-cause deaths. Results There were 17 prostate-cancer-specific deaths overall: 8 in the active-monitoring group (1.5 deaths per 1000 person-years; 95% confidence interval [CI], 0.7 to 3.0), 5 in the surgery group (0.9 per 1000 person-years; 95% CI, 0.4 to 2.2), and 4 in the radiotherapy group (0.7 per 1000 person-years; 95% CI, 0.3 to 2.0); the difference among the groups was not significant (P=0.48 for the overall comparison). In addition, no significant difference was seen among the groups in the number of deaths from any cause (169 deaths overall; P=0.87 for the comparison among the three groups). Metastases developed in more men in the active-monitoring group (33 men; 6.3 events per 1000 person-years; 95% CI, 4.5 to 8.8) than in the surgery group (13 men; 2.4 per 1000 person-years; 95% CI, 1.4 to 4.2) or the radiotherapy group (16 men; 3.0 per 1000 person-years; 95% CI, 1.9 to 4.9) (P=0.004 for the overall comparison). Higher rates of disease progression were seen in the active-monitoring group (112 men; 22.9 events per 1000 person-years; 95% CI, 19.0 to 27.5) than in the surgery group (46 men; 8.9 events per 1000 person-years; 95% CI, 6.7 to 11.9) or the radiotherapy group (46 men; 9.0 events per 1000 person-years; 95% CI, 6.7 to 12.0) (P<0.001 for the overall comparison). Conclusions At a median of 10 years, prostate-cancer-specific mortality was low irrespective of the treatment assigned, with no significant difference among treatments. Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring. (Funded by the National Institute for Health Research; Current Controlled Trials number, ISRCTN20141297 ; ClinicalTrials.gov number, NCT02044172 .).

Concepts: Cancer, Metastasis, Prostate cancer, Urology, Radiation therapy, Screening, Benign prostatic hyperplasia, Prostate-specific antigen

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BACKGROUND: To investigate the effect of prostaglandin depletion by means of COX-inhibition on cholinergic enhanced spontaneous contractions. METHODS: The urethra and bladder of 9 male guinea pigs (weight 270–300 g) were removed and placed in an organ bath with Krebs' solution. A catheter was passed through the urethra through which the intravesical pressure was measured. The muscarinic agonist arecaidine, the non-selective COX inhibitor indomethacin, and PGE2 were subsequently added to the organ bath. The initial average frequency and amplitude of spontaneous contractions in the first 2 minutes after arecaidine application were labelled Fini and Pini, respectively. The steady state frequency (Fsteady) and amplitude (Psteady) were defined as the average frequency and amplitude during the 5 minutes before the next wash out. RESULTS: Application of 1 muM PGE2 increased the amplitude of spontaneous contractions without affecting frequency. 10 muM of indomethacin reduced amplitude but not frequency.The addition of indomethacin did not alter Fini after the first application (p = 0.7665). However, after the second wash, Fini was decreased (p = 0.0005). Fsteady, Psteady and Pini were not significantly different in any of the conditions. These effects of indomethacin were reversible by PGE2 addition.. CONCLUSIONS: Blocking PG synthesis decreased the cholinergically stimulated autonomous contractions in the isolated bladder. This suggests that PG could modify normal cholinergically evoked response. A combination of drugs inhibiting muscarinic receptors and PG function or production can then become an interesting focus of research on a treatment for overactive bladder syndrome.

Concepts: Urine, Urology, Urinary bladder, Urinary system, Urethra, Ureter, Urogenital sinus, Guinea pig

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BACKGROUND: Diabetic patients have a higher risk of bladder cancer and benign prostatic hyperplasia (BPH). Theoretically, BPH patients may have an increased risk of bladder cancer because residual urine in the bladder surely increases the contact time between urinary excreted carcinogens and the urothelium. However, whether BPH increases bladder cancer risk in patients with type 2 diabetes has not been studied. METHODS: The reimbursement databases of all Taiwanese diabetic patients under oral anti-diabetic agents or insulin from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2006 and a total of 547584 men with type 2 diabetes were followed up for bladder cancer incidence until the end of 2009. Incidences of bladder cancer for BPH by status and by duration were calculated and adjusted hazard ratios (95 % confidence intervals) were estimated by Cox regression. The effects of diabetes duration and medications used for diabetic control in relation with bladder cancer risk were also evaluated by Cox regression in BPH men. RESULTS: The incidences were 258.77 and 69.34 per 100,000 person-years for patients with and without BPH, respectively, adjusted hazard ratio 1.794 (1.572, 2.047). For BPH patients, those who underwent surgical procedures for BPH had a higher incidence than those who did not (355.45 vs. 250.09 per 100,000 person-years), respective adjusted hazard ratios: 2.459 (1.946, 3.109) and 1.709 (1.492, 1.958). The significantly higher risk could be demonstrated for BPH of any duration: respective adjusted hazard ratios 1.750 (1.430, 1.605), 1.844 (1.543, 2.203), 2.011 (1.680, 2.406) and 1.605 (1.341, 1.921) for BPH <1, 1--3, 3--5 and >=5 years versus patients without BPH. Sensitivity analyses for patients aged >=60 years and after excluding BPH patients with surgical procedures or without surgical procedures, respectively, yielded similar results. In BPH men, diabetes duration was not significantly related with bladder cancer; but metformin was consistently associated with a significantly lower risk, with adjusted hazard ratio of 0.719 (0.590, 0.875) for all ages and 0.742 (0.604, 0.912) for age >=60 years. CONCLUSIONS: BPH is a significant risk factor for bladder cancer in men with type 2 diabetes. Metformin may protect against bladder cancer in BPH men.

Concepts: Diabetes mellitus type 2, Urine, Obesity, Urology, Urinary bladder, Benign prostatic hyperplasia, Prostate, Urinary retention

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Prostate cancer screening depends on a careful balance of benefits, in terms of reduced prostate cancer mortality, and harms, in terms of overdiagnosis and overtreatment. We aimed to estimate the effect on overdiagnosis of restricting prostate specific antigen (PSA) testing by age and baseline PSA.

Concepts: Cancer, Prostate cancer, Urology, Screening, Prostate, Overdiagnosis, Prostate-specific antigen, Prostate cancer screening

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Extracorporeal shock wave lithotripsy (ESWL) is a first-line treatment for pediatric urinary stone disease. We aimed to determine the factors affecting the outcome of ESWL for unilateral urinary stones in children.

Concepts: Urology, Kidney stone, Lithotriptor

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To analyse the severity profiles and progression criteria in patients diagnosed of benign prostatic hyperplasia (BPH) in urology clinics in Spain.

Concepts: Prostate cancer, Urology, Urinary incontinence, Urination, Benign prostatic hyperplasia, Prostate, Urinary retention, Hyperplasia

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Nano-diamino-tetrac (NDAT) targets a receptor on integrin αvβ3; αvβ3 is generously expressed by cancer cells and dividing endothelial cells and to a small extent by nonmalignant cells. The tetrac (tetraiodothyroacetic acid) of NDAT is covalently bound to a poly(lactic-co-glycolic acid) nanoparticle that encapsulates anticancer drugs. We report NDAT delivery efficiency of cisplatin to agent-susceptible urinary bladder cancer xenografts.

Concepts: Cancer, Oncology, Chemotherapy, Urology, Urinary bladder, Bladder cancer, Cystitis, Hematuria

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Background Robust data on patient-reported outcome measures comparing treatments for clinically localized prostate cancer are lacking. We investigated the effects of active monitoring, radical prostatectomy, and radical radiotherapy with hormones on patient-reported outcomes. Methods We compared patient-reported outcomes among 1643 men in the Prostate Testing for Cancer and Treatment (ProtecT) trial who completed questionnaires before diagnosis, at 6 and 12 months after randomization, and annually thereafter. Patients completed validated measures that assessed urinary, bowel, and sexual function and specific effects on quality of life, anxiety and depression, and general health. Cancer-related quality of life was assessed at 5 years. Complete 6-year data were analyzed according to the intention-to-treat principle. Results The rate of questionnaire completion during follow-up was higher than 85% for most measures. Of the three treatments, prostatectomy had the greatest negative effect on sexual function and urinary continence, and although there was some recovery, these outcomes remained worse in the prostatectomy group than in the other groups throughout the trial. The negative effect of radiotherapy on sexual function was greatest at 6 months, but sexual function then recovered somewhat and was stable thereafter; radiotherapy had little effect on urinary continence. Sexual and urinary function declined gradually in the active-monitoring group. Bowel function was worse in the radiotherapy group at 6 months than in the other groups but then recovered somewhat, except for the increasing frequency of bloody stools; bowel function was unchanged in the other groups. Urinary voiding and nocturia were worse in the radiotherapy group at 6 months but then mostly recovered and were similar to the other groups after 12 months. Effects on quality of life mirrored the reported changes in function. No significant differences were observed among the groups in measures of anxiety, depression, or general health-related or cancer-related quality of life. Conclusions In this analysis of patient-reported outcomes after treatment for localized prostate cancer, patterns of severity, recovery, and decline in urinary, bowel, and sexual function and associated quality of life differed among the three groups. (Funded by the U.K. National Institute for Health Research Health Technology Assessment Program; ProtecT Current Controlled Trials number, ISRCTN20141297 ; ClinicalTrials.gov number, NCT02044172 .).

Concepts: Cancer, Oncology, Prostate cancer, Urology, Radiation therapy, Benign prostatic hyperplasia, Prostate, Hormonal therapy

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Background Salvage radiation therapy is often necessary in men who have undergone radical prostatectomy and have evidence of prostate-cancer recurrence signaled by a persistently or recurrently elevated prostate-specific antigen (PSA) level. Whether antiandrogen therapy with radiation therapy will further improve cancer control and prolong overall survival is unknown. Methods In a double-blind, placebo-controlled trial conducted from 1998 through 2003, we assigned 760 eligible patients who had undergone prostatectomy with a lymphadenectomy and had disease, as assessed on pathological testing, with a tumor stage of T2 (confined to the prostate but with a positive surgical margin) or T3 (with histologic extension beyond the prostatic capsule), no nodal involvement, and a detectable PSA level of 0.2 to 4.0 ng per milliliter to undergo radiation therapy and receive either antiandrogen therapy (24 months of bicalutamide at a dose of 150 mg daily) or daily placebo tablets during and after radiation therapy. The primary end point was the rate of overall survival. Results The median follow-up among the surviving patients was 13 years. The actuarial rate of overall survival at 12 years was 76.3% in the bicalutamide group, as compared with 71.3% in the placebo group (hazard ratio for death, 0.77; 95% confidence interval, 0.59 to 0.99; P=0.04). The 12-year incidence of death from prostate cancer, as assessed by means of central review, was 5.8% in the bicalutamide group, as compared with 13.4% in the placebo group (P<0.001). The cumulative incidence of metastatic prostate cancer at 12 years was 14.5% in the bicalutamide group, as compared with 23.0% in the placebo group (P=0.005). The incidence of late adverse events associated with radiation therapy was similar in the two groups. Gynecomastia was recorded in 69.7% of the patients in the bicalutamide group, as compared with 10.9% of those in the placebo group (P<0.001). Conclusions The addition of 24 months of antiandrogen therapy with daily bicalutamide to salvage radiation therapy resulted in significantly higher rates of long-term overall survival and lower incidences of metastatic prostate cancer and death from prostate cancer than radiation therapy plus placebo. (Funded by the National Cancer Institute and AstraZeneca; RTOG 9601 ClinicalTrials.gov number, NCT00002874 .).

Concepts: Cancer, Metastasis, Prostate cancer, Urology, Radiation therapy, Testosterone, Prostate, Hormonal therapy

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Evidence suggests that ejaculation frequency may be inversely related to the risk of prostate cancer (PCa), a disease for which few modifiable risk factors have been identified.

Concepts: Epidemiology, Cancer, Metastasis, The Canon of Medicine, Prostate cancer, Urology, Radiation therapy, Screening