Sarah Willis

Focal Therapy: Patients, Interventions, and Outcomes—A Report from a Consensus Meeting

Background Focal therapy as a treatment option for localized prostate cancer (PCa) is an increasingly popular and rapidly evolving field. Objective To gather expert opinion on patient selection, interventions, and meaningful outcome measures for focal therapy in clinical practice and trial design. Design, setting, and participants Fifteen experts in focal therapy followed a modified two-stage RAND/University of California, Los Angeles (UCLA) Appropriateness Methodology process. All participants independently scored 246 statements prior to rescoring at a face-to-face meeting. The meeting occurred in June 2013 at the Royal Society of Medicine, London, supported by the Wellcome Trust and the UK Department of Health. Outcome measurements and statistical analysis Agreement, disagreement, or uncertainty were calculated as the median panel score. Consensus was derived from the interpercentile range adjusted for symmetry level. Results and limitations Of 246 statements, 154 (63%) reached consensus. Items of agreement included the following: patients with intermediate risk and patients with unifocal and multifocal PCa are eligible for focal treatment; magnetic resonance imaging–targeted or template-mapping biopsy should be used to plan treatment; planned treatment margins should be 5 mm from the known tumor; prostate volume or age should not be a primary determinant of eligibility; foci of indolent cancer can be left untreated when treating the dominant index lesion; histologic outcomes should be defined by targeted biopsy at 1 yr; residual disease in the treated area of ≤3 mm of Gleason 3 + 3 did not need further treatment; and focal retreatment rates of ≤20% should be considered clinically acceptable but subsequent whole-gland therapy deemed a failure of focal therapy. All statements are expert opinion and therefore constitute level 5 evidence and may not reflect wider clinical consensus. Conclusions The landscape of PCa treatment is rapidly evolving with new treatment technologies. This consensus meeting provides guidance to clinicians on current expert thinking in the field of focal therapy. Patient summary In this report we present expert opinion on patient selection, interventions, and meaningful outcomes for clinicians working in focal therapy for prostate cancer.

Multiparametric MRI followed by targeted prostate biopsy for men with suspected prostate cancer: a clinical decision analysis.

Objective To compare the diagnostic outcomes of the current approach of transrectal ultrasound (TRUS)-guided biopsy in men with suspected prostate cancer to an alternative approach using multiparametric MRI (mpMRI), followed by MRI-targeted biopsy if positive. Design Clinical decision analysis was used to synthesise data from recently emerging evidence in a format that is relevant for clinical decision making. Population A hypothetical cohort of 1000 men with suspected prostate cancer. Interventions mpMRI and, if positive, MRI-targeted biopsy compared with TRUS-guided biopsy in all men. Outcome measures We report the number of men expected to undergo a biopsy as well as the numbers of correctly identified patients with or without prostate cancer. A probabilistic sensitivity analysis was carried out using Monte Carlo simulation to explore the impact of statistical uncertainty in the diagnostic parameters. Results In 1000 men, mpMRI followed by MRI-targeted biopsy ‘clinically dominates’ TRUS-guided biopsy as it results in fewer expected biopsies (600 vs 1000), more men being correctly identified as having clinically significant cancer (320 vs 250), and fewer men being falsely identified (20 vs 50). The mpMRI-based strategy dominated TRUS-guided biopsy in 86% of the simulations in the probabilistic sensitivity analysis. Conclusions Our analysis suggests that mpMRI followed by MRI-targeted biopsy is likely to result in fewer and better biopsies than TRUS-guided biopsy. Future research in prostate cancer should focus on providing precise estimates of key diagnostic parameters.

Synthesis of survival and disease progression outcomes for health technology assessment of cancer therapies

Studies of clinical efficacy commonly report more than one clinical endpoint. For example, randomized controlled trials of treatments for cancer will normally report time to disease progression as well as overall survival. It is likely that disease progression will be associated with higher mortality rates. Disease progression rates will also have consequences for the societal economic burden of the disease. Economic evaluation of the cost-effectiveness of different treatment regimes therefore requires the joint estimation of both disease progression and mortality. We describe a model to combine evidence from studies reporting time to event summaries for disease progression and/or mortality, motivated by a systematic review of 1st-line treatment for advanced breast cancer to provide inputs for an economic evaluation as part of the National Institute for Health and Clinical Excellence (NICE) clinical guideline on treatment of advanced breast cancer in England and Wales. The review identified a network of treatment comparisons, which provides the basis for indirect comparison. A variety of outcomes were reported: overall survival, time to progression (overall and responders only), and the proportion of responder, stable, progressive disease, and non-assessable patients. There were only five trials, and not all trials reported all outcomes. The scarcity of the available evidence required us to make strong assumptions in order to identify model parameters. However, this evidence structure often occurs in health technology assessment (HTA) of treatments for cancer. We discuss the validity of the assumptions made, and the potential to assess their validity in other applications of HTA of cancer therapies. Copyright

A review of economic evaluations of diagnostic strategies using imaging in men at risk of prostate cancer

Purpose of review The role of imaging, particularly MRI, in diagnosing clinically significant prostate cancer is the focus of a rapidly developing body of clinical research. We identified five economic evaluations of multiparametric magnetic resonance imaging (mpMRI) for diagnosing prostate cancer which report very different results. This review aims to explain why the reported cost-effectiveness of mpMRI varies so widely. Findings The studies evaluate the cost-effectiveness of mpMRI within different clinical pathways; before biopsy and after a negative biopsy. Although there were important differences in the questions posed, the studies also employed different assumptions about the impact of prostate cancer and its treatment on survival and quality of life. Summary This review highlights the need for a better standard of reporting around key modelling assumptions. Also, a wider range of sensitivity analyses should explore the impact of these structural assumptions on the model results, in addition to the more commonly acknowledged uncertainty around data inputs for the model parameters.

Methodological considerations in assessing the utility of imaging in early prostate cancer.

Purpose of review An imaging-based pathway, including multiparametric MRI (mpMRI) and magnetic resonance (MR) targeted biopsy, is being increasingly proposed to overcome the shortcomings of the current pathway, based on transrectal ultrasound (TRUS) random biopsy. The purpose of this review is to look at the methodological considerations that need to be addressed prior to widespread adoption of this pathway. Recent findings Novel diagnostic tests should be evaluated in a stepwise fashion with respect to key points: technical accuracy, place in the clinical pathway, diagnostic accuracy, impact on patient outcome and cost-effectiveness. The combination of mpMRI and MR-targeted biopsy has been shown to be superior to TRUS biopsy with regard to most of these key points. mpMRI has the characteristics to be employed as a triage test. MR-targeted biopsy has been consistently shown to be superior to TRUS biopsy in terms of detection of clinically significant disease, utility and efficiency. Before widespread adoption, it is essential to standardize these tests and verify the reproducibility of their performance. Summary Comparative diagnostic studies are consistently in favour of an imaging-based pathway. Once standardization and reproducibility will be verified, it is likely that TRUS biopsy will be implemented, or replaced by mpMRI and MR-targeted biopsy.

Re: Maarten de Rooij, Simone Crienen, J. Alfred Witjes, Jelle O. Barentsz, Maroeska M. Rovers, Janneke P.C. Grutters. Cost-effectiveness of Magnetic Resonance (MR) Imaging and MR-guided Targeted Biopsy Versus Systematic Transrectal Ultrasound-guided Biopsy in Diagnosing Prostate Cancer: A Modelling Study from a Health Care Perspective. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2013.12.012.

Re: Maarten de Rooij, Simone Crienen, J. Alfred Witjes, Jelle O. Barentsz, Maroeska M. Rovers, Janneke P.C. Grutters. Cost-effectiveness of Magnetic Resonance (MR) Imaging and MR-guided Targeted Biopsy Versus Systematic Transrectal Ultrasound–guided Biopsy in Diagnosing Prostate Cancer: A Modelling Study from a Health Care Perspective. Eur Urol. In press. http:// dx.doi.org/10.1016/j.eururo.2013.12.012