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Over 700 men were assigned to radical prostatectomy or observation after receiving a diagnosis of prostate cancer, usually on the basis of elevated PSA levels. After a median of 10 years, between-group differences in all-cause and prostate-cancer mortality were not significant. The treatment of early-stage prostate cancer remains controversial, especially for tumors detected by means of prostate-specific antigen (PSA) testing. 1 Systematic reviews have provided inadequate information for assessing the comparative effectiveness of treatments and any associated harms. 2 Although the lifetime risk of receiving a diagnosis of prostate cancer is about 17%, the risk of dying from the disease is approximately 3%, suggesting that conservative management may be appropriate for many men. 3 , 4 Two randomized trials compared radical prostatectomy with observation but were conducted before PSA testing became widespread. 5 , 6 One study failed to show a significant difference in overall mortality after . . .

The European Randomised study of Screening for Prostate Cancer (ERSPC) has shown significant reductions in prostate cancer mortality after 9 years and 11 years of follow-up, but screening is controversial because of adverse events such as overdiagnosis. We provide updated results of mortality from prostate cancer with follow-up to 2010, with analyses truncated at 9, 11, and 13 years. ERSPC is a multicentre, randomised trial with a predefined centralised database, analysis plan, and core age group (55–69 years), which assesses prostate-specific antigen (PSA) testing in eight European countries. Eligible men aged 50–74 years were identified from population registries and randomly assigned by computer generated random numbers to screening or no intervention (control). Investigators were masked to group allocation. The primary outcome was prostate cancer mortality in the core age group. Analysis was by intention to treat. We did a secondary analysis that corrected for selection bias due to non-participation. Only incidence and no mortality data at 9 years’ follow-up are reported for the French centres. This study is registered with Current Controlled Trials, number ISRCTN49127736. With data truncated at 13 years of follow-up, 7408 prostate cancer cases were diagnosed in the intervention group and 6107 cases in the control group. The rate ratio of prostate cancer incidence between the intervention and control groups was 1·91 (95% CI 1·83–1·99) after 9 years (1·64 [1·58–1·69] including France), 1·66 (1·60–1·73) after 11 years, and 1·57 (1·51–1·62) after 13 years. The rate ratio of prostate cancer mortality was 0·85 (0·70–1·03) after 9 years, 0·78 (0·66–0·91) after 11 years, and 0·79 (0·69–0·91) at 13 years. The absolute risk reduction of death from prostate cancer at 13 years was 0·11 per 1000 person-years or 1·28 per 1000 men randomised, which is equivalent to one prostate cancer death averted per 781 (95% CI 490–1929) men invited for screening or one per 27 (17–66) additional prostate cancer detected. After adjustment for non-participation, the rate ratio of prostate cancer mortality in men screened was 0·73 (95% CI 0·61–0·88). In this update the ERSPC confirms a substantial reduction in prostate cancer mortality attributable to testing of PSA, with a substantially increased absolute effect at 13 years compared with findings after 9 and 11 years. Despite our findings, further quantification of harms and their reduction are still considered a prerequisite for the introduction of populated-based screening. Each centre had its own funding responsibility.

Enzalutamide and abiraterone target the androgen receptor and androgen synthesis and are used to treat castration-resistant prostate cancer. A splice variant of the androgen receptor is associated with resistance to both drugs. It is now accepted that castration-resistant prostate cancer is not androgen-independent and continues to rely on androgen signaling. 1 Owing to this new understanding, several drugs have recently emerged for the treatment of castration-resistant prostate cancer; these agents either suppress the synthesis of extragonadal androgens or target the androgen receptor directly. 2 Enzalutamide is an inhibitor of androgen-receptor signaling that exerts its activity by binding avidly to the ligand-binding domain of the androgen receptor, competing with and displacing the natural ligands of this receptor (testosterone and dihydrotestosterone) while also inhibiting translocation of the androgen receptor into the nucleus and impairing transcriptional activation . . .

In this placebo-controlled trial in children with vesicoureteral reflux after a first or second febrile or symptomatic urinary tract infection, antimicrobial prophylaxis was associated with a substantially reduced risk of recurrence but not of renal scarring. Vesicoureteral reflux is present in one third of children presenting with febrile urinary tract infection and has been associated with a heightened risk of renal scarring. 1 Early randomized, controlled trials that compared antireflux surgery with antimicrobial prophylaxis showed no significant differences in the rates of recurrent urinary tract infection (recurrences) and renal scarring 2 – 5 ; however, the lack of a placebo or observation group precluded a determination that either surgery or prophylaxis was effective. More recent randomized trials, most of which were unblinded, have had conflicting results regarding the effectiveness of antimicrobial prophylaxis in reducing recurrences. 6 – 11 We designed the . . .

In a study involving men with castration-resistant prostate cancer and bone metastases, the alpha emitter radium-223 significantly prolonged survival, as compared with placebo, and was associated with fewer adverse events. More than 90% of patients with metastatic castration-resistant prostate cancer have radiologic evidence of bone metastases, which are a major cause of death, disability, decreased quality of life, and increased treatment cost among these patients. 1 , 2 Unlike deaths from many other types of cancer, deaths from prostate cancer are often due to bone disease and its complications. 3 Current bone-targeted therapies have not been shown to improve survival, and the benefits derived from bisphosphonates, denosumab, and existing radioisotope treatments are primarily limited to pain relief and delay of skeletal events. 4 – 13 Radium-223 dichloride (radium-223) is a targeted alpha emitter that selectively . . .

In this study, the androgen-receptor inhibitor enzalutamide improved progression-free and overall survival in men with castration-resistant metastatic prostate cancer who had not received chemotherapy. Prostate cancer is the most commonly diagnosed cancer and the sixth leading cause of cancer-related death among men worldwide. 1 Strategies to block androgen-receptor signaling have formed the backbone of prostate-cancer therapy since the first description of the hormonal dependence of this cancer in 1941. 2 Advances in endocrine therapies have improved survival in men with high-risk locoregional prostate cancer. 3 , 4 However, new hormonal agents have been shown to extend survival in men with metastatic castration-resistant disease. 5 – 9 In most patients who are treated for advanced recurrent prostate cancer with androgen-deprivation therapy (comprising a luteinizing hormone–releasing hormone [LHRH] analogue or orchiectomy with . . .

Abiraterone has been approved as second-line chemotherapy in patients with metastatic castration-resistant prostate cancer. This study shows significant improvement in progression-free survival with abiraterone as first-line chemotherapy in these patients. Metastatic castration-resistant prostate cancer, defined by tumor growth despite a testosterone level of less than 50 ng per deciliter (1.7 nmol per liter), causes approximately 258,400 deaths annually worldwide. 1 , 2 Death of patients with this condition, which typically occurs within 24 to 48 months after the onset of castration resistance, is commonly preceded by a sequence of landmark events associated with deterioration of overall health and worsening symptoms (Figure S1 in the Supplementary Appendix, available with the full text of this article at NEJM.org). 3 – 7 Among the treatment options for patients with metastatic castration-resistant prostate cancer who have not undergone chemotherapy . . .

The European Randomized Study of Screening for Prostate Cancer continues to show a 21% reduction in prostate-cancer mortality in the screening group, after 11 years of follow-up. The number of cancers that would need to be detected to prevent one prostate-cancer death is 37. Screening does not affect all-cause mortality. Screening for prostate cancer has remained controversial, despite results showing a significant reduction in the rate of death from prostate cancer (relative reduction, 20%) among men offered screening for prostate-specific antigen (PSA). 1 The European Randomized Study of Screening for Prostate Cancer (ERSPC) is a multicenter trial initiated in 1991 in the Netherlands and in Belgium, with five more European countries (Sweden, Finland, Italy, Spain, and Switzerland) joining between 1994 and 1998. Recruitment was completed in these centers between 1995 and 2003. Later, France also joined, with enrollment in 2000–2005, but data from the French cohort were not included in the . . .

In this study involving 1655 men who had been treated for localized prostate cancer, differences between prostatectomy and radiotherapy were noted in the first 5 years after treatment, but these differences tended to disappear after 15 years of follow-up. Patients with clinically localized prostate cancer have a favorable long-term overall and cancer-specific rate of survival regardless of treatment choice. 1 – 3 There are currently no completed prospective, randomized trials that evaluate differences in survival outcomes between radical prostatectomy and external-beam radiation therapy. Consequently, predicted functional outcomes have become essential components of treatment decision making. 4 , 5 Although studies with short-term follow-up (1 to 3 years) and intermediate-term follow-up (4 to 5 years) have identified incremental differences in functional outcomes between patients undergoing prostatectomy and those undergoing radiotherapy, longer-term outcomes remain largely unknown. Since the median life expectancy after treatment for prostate . . .

The randomized Swedish trial of prostatectomy versus watchful waiting in disease detected mainly clinically (not by PSA screening) continues to show a benefit for early prostatectomy. The number of men younger than 65 needed to treat to prevent one death is now four. The Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), a randomized trial of radical prostatectomy versus watchful waiting in men with localized prostate cancer diagnosed before the era of prostate-specific antigen (PSA) testing, showed a survival benefit of radical prostatectomy as compared with observation at 15 years of follow-up. 1 By contrast, the Prostate Cancer Intervention versus Observation Trial (PIVOT), initiated in the early era of PSA testing, showed that radical prostatectomy did not significantly reduce prostate cancer–specific or overall mortality after 12 years. 2 PSA screening profoundly changes the clinical domain of study. Among other considerations, the substantial additional lead time . . .