Radical prostatectomy versus deferred treatment for localised prostate cancer.

BACKGROUND: Prostate cancer is a common cancer but is oftentimes slow growing. When confined to the prostate, radical prostatectomy (RP), which involves removal of the prostate, offers potential cure that may come at the price of adverse events. Deferred treatment, involving observation and palliative treatment only (watchful waiting (WW)) or close monitoring and delayed local treatment with curative intent as needed in the setting of disease progression (active monitoring (AM)/surveillance (AS)) might be an alternative. This is an update of a Cochrane Review previously published in 2010. OBJECTIVES: To assess effects of RP compared with deferred treatment for clinically localised prostate cancer. SEARCH METHODS: We searched the Cochrane Library (including CDSR, CENTRAL, DARE, and HTA), MEDLINE, Embase, AMED, Web of Science, LILACS, Scopus, and OpenGrey. Additionally, we searched two trial registries and conference abstracts of three conferences (EAU, AUA, and ASCO) until 3 March 2020. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that compared RP versus deferred treatment in patients with localised prostate cancer, defined as T1-2, N0, M0 prostate cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of references and extracted data from included studies. The primary outcome was time to death from any cause; secondary outcomes were: time to death from prostate cancer; time to disease progression; time to metastatic disease; quality of life, including urinary and sexual function; and adverse events. We assessed the certainty of evidence per outcome using the GRADE approach.  MAIN RESULTS: We included four studies with 2635 participants (average age between 60 to 70 years). Three multicentre RCTs, from Europe and USA, compared RP with WW (n = 1537), and one compared RP with AM (n = 1098). Radical prostatectomy versus watchful waiting RP probably reduces the risk of death from any cause (hazard ratio (HR) 0.79, 95% confidence interval (CI) 0.70-0.90; 3 studies with 1537 participants; moderate-certainty evidence). Based on overall mortality at 29 years, this corresponds to 764 deaths per 1000 men in the RP group compared to 839 deaths per 1000 men in the WW group. RP probably also lowers the risk of death from prostate cancer (HR 0.57, 95% CI 0.44-0.73; 2 studies with 1426 participants; moderate-certainty evidence). Based on prostate cancer-specific mortality at 29 years, this corresponds to 195 deaths from prostate cancer per 1000 men in the RP group compared with 316 deaths from prostate cancer per 1000 men in the WW group. RP may reduce the risk of progression (HR 0.43, 95% CI 0.35-0.54; 2 studies with 1426 participants; I² = 54%; low-certainty evidence); at 19.5 years, this corresponds to 391 progressions per 1000 men for the RP group compared with 684 progressions per 1000 men for the WW group) and probably reduces the risk of developing metastatic disease (HR 0.56, 95% CI 0.46-0.70; 2 studies with 1426 participants; I² = 0%; moderate-certainty evidence); at 29 years, this corresponds to 271 metastatic diseases per 1000 men for RP compared with 431 metastatic diseases per 1000 men for WW. General quality of life at 12 years' follow-up is probably similar for both groups (risk ratio (RR) 1.0, 95% CI 0.85-1.16; low-certainty evidence), corresponding to 344  patients with high quality of life per 1000 men for the RP group compared with 344 patients with high quality of life per 1000 men for the WW group. Rates of urinary incontinence may be considerably higher (RR 3.97, 95% CI 2.34-6.74; low-certainty evidence), corresponding to 173 incontinent men per 1000 in the RP group compared with 44 incontinent men per 1000 in the WW group, as are rates of erectile dysfunction (RR 2.67, 95% CI 1.63-4.38; low-certainty evidence), corresponding to 389 erectile dysfunction events per 1000 for the RP group compared with 146 erectile dysfunction events per 1000 for the WW group, both at 10 years' follow-up. Radical prostatectomy versus active monitoring Based on one study including 1098 participants with 10 years' follow-up, there are probably no differences between RP and AM in time to death from any cause (HR 0.93, 95% CI 0.65-1.33; moderate-certainty evidence). Based on overall mortality at 10 years, this corresponds to 101 deaths per 1000 men in the RP group compared with 108 deaths per 1000 men in the AM group. Similarly, risk of death from prostate cancer probably is not different between the two groups (HR 0.63, 95% CI 0.21-1.89; moderate-certainty evidence). Based on prostate cancer-specific mortality at 10 years, this corresponds to nine prostate cancer deaths per 1000 men in the RP group compared with 15 prostate cancer deaths per 1000 men in the AM group. RP probably reduces the risk of progression (HR 0.39, 95% CI 0.27-0.56; moderate-certainty evidence; at 10 years, this corresponds to 86 progressions per 1000 men for RP compared with 206 progressions per 1000 men for AM) and the risk of developing metastatic disease (RR 0.39, 95% CI 0.21-0.73; moderate-certainty evidence; at 10 years, this corresponds to 24 metastatic diseases per 1000 men for the RP group compared with 61 metastatic diseases per 1000 men for the AM group).The general quality of life during follow-up was not different between the treatment groups. However, urinary function (mean difference (MD) 8.60 points lower, 95% CI 11.2-6.0 lower) and sexual function (MD 14.9 points lower, 95% CI 18.5-11.3 lower) on the Expanded Prostate Cancer Index Composite-26 (EPIC-26) instrument, were worse in the RP group. AUTHORS' CONCLUSIONS: Based on long-term follow-up, RP compared with WW probably results in substantially improved oncological outcomes in men with localised prostate cancer but also markedly increases rates of urinary incontinence and erectile dysfunction. These findings are largely based on men diagnosed before widespread PSA screening, thereby limiting generalisability. Compared to AM, based on follow-up to 10 years, RP probably has similar outcomes with regard to overall and disease-specific survival yet probably reduces the risks of disease progression and metastatic disease. Urinary function and sexual function are probably decreased for the patients treated with RP.

Guideline of guidelines: primary monotherapies for localised or locally advanced prostate cancer.

Decisions regarding the primary treatment of prostate cancer depend on several patient- and disease-specific factors. Several international guidelines regarding the primary treatment of prostate cancer exist; however, they have not been formally compared. As guidelines often contradict each other, we aimed to systematically compare recommendations regarding the different primary treatment modalities of prostate cancer between guidelines. We searched Medline, the National Guidelines Clearinghouse, the library of the Guidelines International Network, and the websites of major urological associations for prostate cancer treatment guidelines. In total, 14 guidelines from 12 organisations were included in the present article. One of the main discrepancies concerned the definition of 'localised' prostate cancer. Localised prostate cancer was defined as cT1-cT3 in most guidelines; however, this disease stage was defined in other guidelines as cT1-cT2, or as any T-stage as long as there is no lymph node involvement (N0) or metastases (M0). In addition, the risk stratification of localised cancer differed considerably between guidelines. Recommendations regarding radical prostatectomy and hormonal therapy were largely consistent between the guidelines. However, recommendations regarding active surveillance, brachytherapy, and external beam radiotherapy varied, mainly as a result of the inconsistencies in the risk stratification. The differences in year of publication and the methodology (i.e. consensus-based or evidence-based) for developing the guidelines might partly explain the differences in recommendations. It can be assumed that the observed variation in international clinical practice regarding the primary treatment of prostate cancer might be partly due to the inconsistent recommendations in different guidelines.

Selective outcome reporting across psychopharmacotherapy randomized controlled trials.

OBJECTIVE: Selective reporting impairs the valid interpretation of trials and leads to bias with regards to the clinical evidence. We aimed to examine factors associated with selective reporting in psychopharmacotherapy trials and thus enable solutions to prevent such selective reporting in the future. METHODS: We retrieved all registry records of trials investigating medication for depressive, bipolar and psychotic disorders. Multivariate logistic regression was performed with selective reporting as outcome, and funding source, psychiatric disorder, year of study start date, participating centers, and anticipated sample size as explanatory variables, after testing for multicollinearity. Adjusted odds ratios (AOR) were calculated. Two-sided Fisher exact test was used to compare the proportions of newly added positive primary outcomes with the proportions of positive results in the overall group of primary outcomes. RESULTS: Of 151 included trials (N = 94,303 participants), 21 (14%) showed irregularities between registered and published primary outcomes. Higher odds of such irregularities were associated with non-industry-funded RCTs (AOR 5.3; p = 0.014) and trials investigating major depressive disorder (AOR 12.7; p = 0.024) or schizophrenia (AOR 14.5; p = 0.016; Table 1). CONCLUSION: We demonstrate discrepancies between trial registrations and publications across RCTs investigating debilitating psychiatric disorders, especially in non-industry funded RCTs.