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Low Risk Prostate Cancer and Active Surveillance
Get PDFThe first part of this thesis comprises an introduction to prostate cancer and screening (chapter 1). The European Randomized study of Screening for Prostate Cancer (ERSPC) has shown an effect of screening on prostate cancer mortality in favor of the screening population, however, controversies remain. One of the most important side-effects of screening is overdiagnosis with subsequent overtreatment, which has led to the introduction of active surveillance as an alternative to the radical treatment of prostate cancer (chapter 2). With active surveillance, patients with supposedly low-risk tumors receive expectant management and are strictly followed over time. In case of reclassification to higher risk or signs of true disease progression, the patient will switch to deferred radical treatment. Because active surveillance is a relatively new management strategy, its feasibility and the short-term outcomes are the main focus of this thesis (chapter 3).
The second part of this thesis focuses on low-risk prostate cancer. In chapter 4 the main findings of the ERSPC are described and the controversial points in prostate cancer screening are discussed, as well as how these issues should be dealt with. Overdiagnosis and overtreatment are indicated as major worries, but less aggressive screening methods, risk modifying calculators and the use of active surveillance can decrease the impact of these side-effects and, if applied, will lead to a better risk-benefit ratio in screening. In chapter 5, it is shown that the risk of developing prostate cancer, aggressive prostate cancer and prostate cancer death in men with initial PSA values 3.0 ng/ml (11-fold higher) and compared to the risk of other causes of death (150-fold higher). Especially men with PSA <1.0 ng/ml at first screen had a minimal risk to die from prostate cancer during an 11 year period. This finding supports the idea to prolong the screening interval to at least 8 years in this group. The overall outcomes of this study contribute to risk stratification and individual management of men in PSA-based screening programs. The long-term feasibility of expectant management as a proxy for active surveillance in contemporary practice is assessed in chapter 6 by evaluating outcomes of men with screen-detected localized prostate cancer who initially elected to withhold radical treatment for either low- or intermediate-risk disease. Although intermediate-risk men, by definition, had more unfavorable disease characteristics at diagnosis, their 10-year disease-specific survival rates did not differ from the low-risk group. The overall outcomes were favorable with a 98.4% disease-specific survival rate for the overall cohort, while radical treatment was avoided in a majority of cases. These results support the feasibility for active surveillance on the longer-term and even show that selected patients with intermediate-risk disease might profit from this strategy.
In part three, chapter 7, an effort is made to calculate correction factors based on autopsy data for the use of the prostate cancer risk calculator in contemporary practice. The original risk calculator is based on sextant biopsies, while nowadays often more biopsy cores are taken. Adjustments correcting for this increase would lead to a more accurate prediction of the probability of indolent cancer. Correction factors for 12 and 18-core schemes were calculated; however, the small number of patients and the lack of validation hamper implementation of the results and reinforce the need for further study.
Part four shows the results of the Prostate Cancer Research International: Active Surveillance (PRIAS) trial. Chapter 8 focuses on the outcome of the routinely obtained 1-year repeat biopsies and identifying prognosticators for unfavorable results. Risk reclassification to higher risk was found in 163 out of 757 (21.5%) repeat biopsies. The outcome was found to be significantly associated with the number of positive cores (2 vs. 1) and PSA density at diagnosis, as well as PSA doubling time at the time of repeat biopsy. Though reclassification is quite common and more likely due to misclassification than to actual disease progression, the relatively high rate emphasizes the difficulty of patient selection and the need for continued evaluation in active surveillance. Results of this study show that clinical features at baseline and during follow-up can be used in risk stratification of men for the prediction of unfavorable features at repeat biopsy. Radical prostatectomy results after initial active surveillance are described in chapter 9. The majority of men showed organ-confined disease and favorable Gleason grading (<3+4) in a majority of cases. Nevertheless, 29% (49/167) were found to have an unfavorable radical prostatectomy outcome. Since median time to surgery was quite short (1.3 years), it is likely that that most of the cases with unfavorable outcome were misclassified at diagnosis. More than 75% of this cohort switched to surgery based on a protocol recommendation, which may, at least in part, explain the relatively high rate of unfavorable findings due to the self-selection of men who start on active surveillance and receive surgery because of reclassification during follow-up. These results again show the importance of improvement in patient selection for active surveillance. Chapter 10 gives an up-to-date overview of the PRIAS study. Short-term data confirm the feasibility of active surveillance in the reduction of overtreatment and the use of a web-based tool to facilitate worldwide inclusion of patients. Clinical characteristics at baseline and PSA kinetics are again shown to be predictive for reclassification, as well as for switching to deferred treatment. The active therapy-free survival after 2 and 4 years was found to be 77.3% and 67.7%, respectively. The disease-specific survival rate was 100%, but follow-up is still too short to draw definitive conclusions. Finally, in chapter 11, an overview is presented of key issues in active surveillance that need to be tackled and emerging technologies and markers that will hopefully lead to optimization of patient selection and care in the near future.
The fifth part of this thesis summarizes and discusses the key findings of the studies described in all previous chapters and puts them into perspective (chapter 12). The rationale for active surveillance and the feasibility of this strategy are discussed in more detail. An overview of contemporary active surveillance trials is presented and the areas of improvement are indicated. Eventually, a balance needs to be found between maximizing the number of patients who can avoid treatment and minimizing the number of aggressive prostate cancer missed. The improvement of screening strategies and developments in the technologies for radical treatment in the future might lead to decreased rates of overdiagnosis and virtual disappearance of side-effects, which in turn would reduce the need for active surveillance as an alternative to radical treatment. Until then, research aimed at improving active surveillance strategies will continue and we will carry on providing the best care available today to our patients
Reply from authors re: Peter C. Albertsen. How best to use our tools?:Eur Urol 2012;62:201-2
No full textWe appreciate the comments from Albertsen in response to our paper. He highlighted some of the controversies and obstacles in prostate cancer (PCa) screening that have yet to be conquered. Although it has been shown that screening for PCa can reduce disease-specific mortality by up to 30% or even more, the shortcomings of screening regarding the number of false-positive tests and overdiagnosis are evident. Hence we are aware of the side effects of screening, and the challenge we face is to look for solutions.There is still a lot of work to do in finding new, better, and more selective markers for screening purposes and to keep improving nomograms for risk stratification to achieve better predictions. Ideally, either there would be no overdetection of disease that will not surface clinically during the patient's lifetime or radical treatment would be free from any side effects. Unfortunately, [...
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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