Predictive role of free prostate-specific antigen in a prospective active surveillance program (PRIAS)

To evaluate the utility of percentage of free serum PSA (%fPSA) as a predictor of adverse rebiopsy findings, treatment change and radical prostatectomy (RP) findings in a prospective active surveillance (AS) trial. Patients enrolled in the global PRIAS study with baseline %fPSA available were included. Putative baseline predictors (e.g. PSA, %fPSA) of adverse rebiopsy findings were explored using logistic regression analysis. Association of variables with treatment change and RP findings over time were evaluated with Cox regression analysis. Active treatment-free survival was assessed with a Kaplan-Meier method. Of 3701 patients recruited to PRIAS, 939 had %fPSA measured at study entry. Four hundred and thirty-eight of them had %fPSA available after 1 year. Median follow-up was 17.2 months. First rebiopsy results were available for 595 patients and of those, 144 (24.2 %) had adverse findings. A total of 283 (30.1 %) patients discontinued surveillance, of those 181 (64.0 %) due to protocol-based reasons. Although median %fPSA values were significantly lower in patients who changed treatment, according to the multivariate regression analysis, initial %fPSA value was not predictive for treatment change or adverse rebiopsy findings. However, the probability of discontinuing AS was significantly lower in patients with "favourable" initial %fPSA characteristics and %fPSA during follow-up (initial %fPSA a parts per thousand yen15 and positive %fPSA velocity) compared to those with "adverse" %fPSA characteristics (initial %fPSA <15 and negative %fPSA velocity). Diagnostic %fPSA provides no additional prognostic value when compared to other predictors already in use in AS protocols. However, %fPSA velocity during surveillance may aid in predicting the probability for future treatment change.Peer reviewe

Prostate Specific Antigen as a Tumor Marker in Prostate Cancer: Biochemical and Clinical Aspects

In this chapter the use of prostate specific antigen (PSA) as a tumor marker for prostate cancer is discussed. The chapter provides an overview of biological and clinical aspects of PSA. The main drawback of total PSA (tPSA) is its lack of specificity for prostate cancer which leads to unnecessary biopsies. Moreover, PSA-testing poses a risk of overdiagnosis and subsequent overtreatment. Many PSA-based markers have been developed to improve the performance characteristics of tPSA. As well as different molecular subforms of tPSA, such as proPSA (pPSA) and free PSA (fPSA), and PSA derived kinetics as PSA-velocity (PSAV) and PSA-doubling time (PSADT). The prostate health index (phi), PSA-density (PSAD) and the contribution of non PSA-based markers such as the urinary transcripts of PCA3 and TMPRSS-ERG fusion are also discussed. To enable further risk stratification tumor markers are often combined with clinical data (e.g. outcome of DRE) in so-called nomograms. Currently the role of magnetic resonance imaging (MRI) in the detection and staging of prostate cancer is being explored

Differences in Treatment and Outcome After Treatment with Curative Intent in the Screening and Control Arms of the ERSPC Rotterdam

Screening for prostate cancer (PCa) results in a favorable stage shift. However, even if screening did not result in a clinically apparent lower stage or grade, it might still lead to less disease recurrence after treatment with curative intent (radical prostatectomy [RP] and radiation therapy [RT]) because the tumor had less time to develop outside the prostate. The outcome after treatment could also differ because of variations in treatment quality (eg, radiation dosage/adjuvant hormonal therapy). To test these hypotheses, we compared differences in the treatment quality of the screening and control arms of the European Randomized Study of Screening for Prostate Cancer (ERSPC) Rotterdam and disease-free survival (DFS) after curative treatment in PCa patients with similar stage and grade. A total of 2595 men were initially treated with RP or RT. In the control arm, RT was more often combined with hormonal therapy; treatment dosage was often >= 69 Gy. This most likely resulted from changes over time in treatment that coincided with the later detection in the control arm. DFS was higher in the screening arm in all risk groups. After correction for lead time, these differences were minimal, however. We concluded that treatment quality differed between the screening and control arms of the ERSPC Rotterdam. RT quality was especially superior in the control arm with higher dosages and more often RT in combination with hormonal therapy. Despite these differences favoring the control arm, DFS differences were minimal. Patient summary: We looked at differences in prostate cancer (PCa) treatment and outcome after PCa treatment in men diagnosed after screening and men diagnosed after normal clinical practice. Treatment differed with superior treatment given to men diagnosed in normal clinical practice. We propose a likely explanation for this apparently counterintuitive finding (progressive insight combined with, on average, a later detection of tumors in unscreened men). Although unscreened men received better treatment, this advantage seemed to be outweighed by the advantage associated with the earlier detection, on average, of the tumor in screened men. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved

The Ontological (In)security of Similarity: Wahhabism versus Islamism in Saudi Foreign Policy

It has long been argued that identity matters in international relations. Yet, how identity impacts enmity and conflict among states remains the subject of debate. The existing literature asserts that differences in identity can be a source of conflict, whereas convergence and similarity lead to cooperation. Nevertheless, empirical evidence from the Middle East has long defied this hypothesis. The Kingdom of Saudi Arabia, which prides itself on being an Islamic model and claims Islamic leadership, has opposed the rise to power of Islamist movements in the Middle East. To address this paradox, this article builds on the growing literature on ontological security to propose a theoretical framework explaining how similarity can generate anxiety and identity risks. This framework, I argue, moves beyond traditional regime‐security approaches to reveal that security is not only physical but also ontological. I then illustrate the argument through a comparison of Saudi identity risks in the wake of the Iranian revolution (1979) and the ascendance of the Muslim Brotherhood to power in Egypt (2012). Ultimately, these cases provide intriguing insights into foreign policy behaviour during critical situations

How Many Replicators Does It Take to Achieve Reliability? Investigating Researcher Variability in a Crowdsourced Replication

The paper reports findings from a crowdsourced replication. Eighty-four replicator teams attempted to verify results reported in an original study by running the same models with the same data. The replication involved an experimental condition. A “transparent” group received the original study and code, and an “opaque” group received the same underlying study but with only a methods section and description of the regression coefficients without size or significance, and no code. The transparent group mostly verified the original study (95.5%), while the opaque group had less success (89.4%). Qualitative investigation of the replicators’ workflows reveals many causes of non-verification. Two categories of these causes are hypothesized, routine and non-routine. After correcting non-routine errors in the research process to ensure that the results reflect a level of quality that should be present in ‘real-world’ research, the rate of verification was 96.1 in the transparent group and 92.4 in the opaque group. Two conclusions follow: (1) Although high, the verification rate suggests that it would take a minimum of three replicators per study to achieve replication reliability of at least 95 confidence assuming ecological validity in this controlled setting, and (2) like any type of scientific research, replication is prone to errors that derive from routine and undeliberate actions in the research process. The latter suggests that idiosyncratic researcher variability might provide a key to understanding part of the “reliability crisis” in social and behavioral science and is a reminder of the importance of transparent and well documented workflows