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Background: Active surveillance (AS) for low-risk prostate cancer (PCa) appears to provide excellent long-term PCa-specific and overall survival. The choice for AS as initial treatment is mainly based on avoiding side effects from invasive treatment; but AS entails regular check-ups and the possibility of still having to switch or deciding to switch to invasive treatment. Here, we assessed the long-term follow-up data from AS in real life clinical practices. Methods: Data from the first 500 men, enrolled in PRIAS before July 2008 by 30 centers across 8 countries, were analyzed to provide long-term follow-up results. Men were advised to be regularly examined with prostate-specific antigen (PSA) tests, digital rectal examinations, and prostate biopsies. Men were advised to switch to invasive treatment if they had disease reclassification [Gleason score (GS) >= 3+ 4 on biopsy, more than two positive biopsy cores, a stage higher than cT2] or a PSA-doubling time of 0-3 years. We assessed time on AS, outcomes and reasons for discontinuing AS, and rates of potential unnecessary biopsies and treatments. Results: The median follow-up time was 6.5 years. During this period, 325 (65%) men discontinued after a median of 2.3 years and 121 (24%) men had no recent (> 1 year) data-update after a median of 7.3 years. The remaining 54 (11%) men were confirmed to be still on AS. Most men discontinued based on protocol advice; 38% had other reasons. During follow-up, 838 biopsy sessions were performed of which 79% to 90% did not lead to reclassification, depending on the criteria. Of the 325 discontinued men, 112 subsequently underwent radical prostatectomy (RP), 126 underwent radiotherapy, 57 switched to watchful waiting (WW) or died, and 30 had another or unknown treatment. RP results were available of 99 men: 34% to 68%, depending on definition, had favorable outcomes; 50% of unfavorable the outcomes occurred in the first 2 years. Of the 30 (6%) men who died, 1 man died due to PCa. Conclusions: These data, reflecting real life clinical practice, show that more than half of men switched to invasive treatment within 2.3 years, indicating limitations to the extent in which AS is able to reduce the adverse effects of overdiagnosis. Therefore, despite guidelines stating that PCa diagnosis must be uncoupled from treatment, it remains important to avoid overdiagnosing PCa as much as possible.

Objectives: The Movember Foundation launched the Global Action Plan Prostate Cancer Active Surveillance (GAP3) initiative to create a global consensus on the selection and monitoring of men with low-risk prostate cancer (PCa) on active surveillance (AS). The aim of this study is to present data on inclusion and follow-up for AS in this unique global AS database. Patients and Methods: Between 2014 and 2016, the database was created by combining patient data from 25 established AS cohorts worldwide (USA, Canada, Australasia, UK and Europe). Data on a total of 15 101 patients were included. Descriptive statistics were used to report patients' clinical and demographic characteristics at the time of PCa diagnosis, clinical follow-up, discontinuation of AS and subsequent treatment. Cumulative incidence curves were used to report discontinuation rates over time. Results: At diagnosis, the median (interquartile range [IQR]) patient age was 65 (60–70) years and the median prostate-specific antigen level was 5.4 (4.0–7.3) ng/mL. Most patients had clinical stage T1 disease (71.8%), a biopsy Gleason score of 6 (88.8%) and one tumour-positive biopsy core (60.3%). Patients on AS had a median follow-up time of 2.2 (1.0–5.0) years. After 5, 10 and 15 years of follow-up, respectively, 58%, 39% and 23% of patients were still on AS. The current version of GAP3 has limited data on magnetic resonance imaging (MRI), quality of life and genomic testing. Conclusions: GAP3 is the largest worldwide collaboration integrating patient data from men with PCa on AS. The results will allow individual patients and clinicians to have greater confidence in the personalized decision to either delay or proceed with active treatment. Longer follow-up and the evaluation of MRI, new genomic markers and patient-related outcomes will result in even more valuable data and eventually in better patient outcomes.

Active surveillance (AS) is broadly described as a management option for men with low-risk prostate cancer, but semantic heterogeneity exists in both the literature and in guidelines. To address this issue, a panel of leading prostate cancer specialists in the field of AS participated in a consensus-forming project using a modified Delphi method to reach international consensus on definitions of terms related to this management option. An iterative three-round sequence of online questionnaires designed to address 61 individual items was completed by each panel member. Consensus was considered to be reached if ≥70% of the experts agreed on a definition. To facilitate a common understanding among all experts involved and resolve potential ambiguities, a face-to-face consensus meeting was held between Delphi survey rounds two and three. Convenience sampling was used to construct the panel of experts. In total, 12 experts from Australia, France, Finland, Italy, the Netherlands, Japan, the UK, Canada and the USA participated. By the end of the Delphi process, formal consensus was achieved for 100% (n = 61) of the terms and a glossary was then developed. Agreement between international experts has been reached on relevant terms and subsequent definitions regarding AS for patients with localized prostate cancer. This standard terminology could support multidisciplinary communication, reduce the extent of variations in clinical practice and optimize clinical decision making.

Joint modelling of longitudinal and survival data is increasingly used in clinical trials on cancer. In prostate cancer for example, these models permit to account for the link between longitudinal measures of prostate-specific antigen (PSA) and the time of clinical recurrence when studying the risk of relapse. In practice, multiple types of relapse may occur successively. Distinguishing these transitions between health states would allow to evaluate, for example, how PSA trajectory and classical covariates impact the risk of dying after a distant recurrence post-radiotherapy, or to predict the risk of one specific type of clinical recurrence post-radiotherapy, from the PSA history. In this context, we present a joint model for a longitudinal process and a multi-state process which is divided into two sub-models: a linear mixed sub-model for longitudinal data, and a multi-state sub-model with proportional hazards for transition times, both linked by shared random effects. Parameters of this joint multi-state model are estimated within the maximum likelihood framework using an EM algorithm coupled to a quasi-Newton algorithm in case of slow convergence. It is implemented under R, by combining and extending the mstate and JM packages. The estimation program is validated by simulations and applied on pooled data from two cohorts of men with localized prostate cancer and treated by radiotherapy. Thanks to the classical covariates available at baseline and the PSA measurements collected repeatedly during the follow-up, we are able to assess the biomarker's trajectory, define the risks of transitions between health states, and quantify the impact of the PSA dynamics on each transition intensity., Added appendix

Patients who were previously treated for prostate cancer with radiation therapy are monitored at regular intervals using a laboratory test called Prostate Specific Antigen (PSA). If the value of the PSA test starts to rise, this is an indication that the prostate cancer is more likely to recur, and the patient may wish to initiate new treatments. Such patients could be helped in making medical decisions by an accurate estimate of the probability of recurrence of the cancer in the next few years. In this article, we describe the methodology for giving the probability of recurrence for a new patient, as implemented on a web-based calculator. The methods use a joint longitudinal survival model. The model is developed on a training dataset of 2386 patients and tested on a dataset of 846 patients. Bayesian estimation methods are used with one Markov chain Monte Carlo (MCMC) algorithm developed for estimation of the parameters from the training dataset and a second quick MCMC developed for prediction of the risk of recurrence that uses the longitudinal PSA measures from a new patient.

Objective The purpose of this investigation was to explicate the content of primary treatment consultations in prostate oncology and examine the predictive relationships between patient, significant other, and oncologist consultation factors and patient satisfaction with communication. Methods The recorded consultations of 156 newly diagnosed prostate cancer patients from three Canadian cancer centers were examined using the Medical Interaction Process System (MIPS). The MIPS findings, independent observer ratings of patient, significant other, and oncologist affective behavior, and derived consultation ratios of patient centeredness, patient directedness, and psychosocial focus, were used to predict patient satisfaction with communication post-consultation and at 12-weeks post-consultation. Results Biomedical content categories were predominant in the consultations, accounting for 86% of utterances, followed by administrative (9%) and psychosocial (5%) utterances. Post-consultation satisfaction with communication was significantly lower for patients whose significant others were rated as more assertive during the consultation, and those rated as more anxious during the consultation. Patients who were rated as more anxious during the consultation, those with lower satisfaction with communication immediately post-consultation and those with shorter consultations were significantly less satisfied with communication at 12-weeks post-consultation. Conclusions Adjuvant treatment consultations in prostate oncology are characterized by a high degree of information-giving by the physician, a predominance of biomedical discussion, and relatively minimal time addressing patients' psychosocial concerns. Patients may benefit from oncologists who address anxiety and emotional distress during the primary treatment consultation, allowing sufficient time to ensure that patients leave the consultation with their communication needs having been satisfied. Copyright © 2011 John Wiley & Sons, Ltd. Copyright © 2011 John Wiley & Sons, Ltd.

International audience; PURPOSE: To estimate the α/β ratio of prostate cancer treated with external beam radiation only by use of a model of long-term prostate-specific antigen (PSA) dynamics. METHODS AND MATERIALS: Repeated measures of PSA from 5,093 patients from 6 institutions treated for localized prostate cancer by external beam radiation therapy (EBRT) without planned androgen deprivation were analyzed. A biphasic linear mixed model described the post-treatment evolution of PSA, rather than a conventional model of time to biochemical recurrence. The model was adjusted for standard prognostic factors (T stage, initial PSA level, and Gleason score) and cohort-specific effects. The radiation dose fractionation effect was estimated from the long-term rate of rise of PSA level. RESULTS: Adjusted for other factors, total dose of EBRT and sum of squared doses per fraction were associated with long-term rate of change of PSA level (p = 0.0017 and p = 0.0003, respectively), an increase of each being associated with a lower rate of rise. The α/β ratio was estimated at 1.55 Gy (95% confidence band, 0.46-4.52 Gy). This estimate was robust to adjustment of the linear mixed model. CONCLUSIONS: By analysis of a large EBRT-only cohort along with a method that uses all the repeated measures of PSA after the end of treatment, a low and precise α/β was estimated. These data support the use of hypofractionation at fractional doses up to 2.8 Gy but cannot presently be assumed to accurately represent higher doses per fraction.

Objective: The purpose of this investigation was to explicate the content of primary adjuvant treatment consultations in breast oncology and examine the predictive relationships between patient and oncologist consultation factors and patient satisfaction with communication. Methods: The recorded consultations of 172 newly diagnosed breast cancer patients from four Canadian cancer centers were randomly drawn from a larger subset of 481 recordings and examined by three coders using the Medical Interaction Process System (MIPS); a system that categorizes the content and mode of each distinct utterance. The MIPS findings, independent observer ratings of patient and oncologist affective behavior, and derived consultation ratios of patient centeredness, patient directedness, and psychosocial focus, were used to predict patient satisfaction with communication post-consultation and at 12-weeks post-consultation. Results: Biomedical content categories were predominant in the consultations, accounting for 88% of all utterances, followed by administrative (6%) and psychosocial (6%) utterances. Post-consultation satisfaction with communication was significantly higher for older patients, those with smaller primary tumors and those with longer consultations. Smaller tumor, lack of patient assertiveness during the treatment consultation and having the consultation with a radiation rather than medical oncologist were significantly predictive of greater satisfaction at 12-weeks post-consultation. Conclusions: Adjuvant treatment consultations are characterized by a high degree of informationgiving by the physician, a predominance of biomedical discussion and relatively minimal time addressing patients' psychosocial concerns. Controlled trials are needed to further identify and address the contextual features of these consultations that enhance patient satisfaction. Copyright © 2009 John Wiley & Sons, Ltd.

Purpose: The purpose of this secondary investigation was to examine the impact of the type of treatment received and the perceived role in treatment decision making in predicting distress and cancer-specific quality of life in patients newly diagnosed with breast or prostate cancer. Method: Participants included 1057 newly diagnosed breast and prostate cancer patients from four Canadian cancer centers who partook in a randomized controlled trial examining the utility of providing patients with an audio-recording of their treatment planning consultation. A MANCOVA was performed to predict distress and cancer-specific quality of life at 12 weeks post-consultation based on control variables (patient age, education, residence, tumor size (breast sample), gleason score (prostate sample), and receipt of an initial treatment consultation recording), predictor variables (treatment type - chemotherapy, hormone therapy, radiation therapy; decisional role - active, collaborative, passive), and interactions between these predictors. Results: Women who received chemotherapy and reported having played a more passive role in treatment decision making had significantly greater distress and lower cancer-specific quality of life at 12-week post-consultation. There were no statistically significant predictors of these outcomes identified for men with prostate cancer. Conclusion: Receipt of chemotherapy places women with breast cancer at risk for distress and reduced quality of life, but only for the subset of women who report playing a passive role in treatment decision making. Prospective, longitudinal studies are needed to confirm the present findings and to explicate the antecedents, composition, and consequences of the 'passive' decisional role during the treatment phase of the cancer trajectory. Copyright © 2009 John Wiley & Sons, Ltd.

Purpose To assess whether an expanded (five level) risk stratification system can be used to identify the sub-group of intermediate risk patients with prostate cancer who benefit from combining androgen deprivation therapy (ADT) with external beam radiotherapy (EBRT). Materials and methods Using a previously validated 5-risk group schema, a prospective non-randomized data set of 1423 men treated at the British Columbia Cancer Agency was assessed for the primary end point of biochemical control (bNED) with the RTOG-ASTRO "Phoenix" definition (lowest PSA to date + 2 ng/mL), both with and without adjuvant ADT. The median follow-up was 5 years. Results There was no bNED benefit for ADT in the low or low intermediate groups but there was a statistically significant bNED benefit in the high intermediate, high and extreme risk groups. The 5-year bNED rates with and without ADT were 70% and 73% respectively for the low intermediate group (p = non-significant) and 72% and 58% respectively for the high intermediate group (p = 0.002). Conclusion There appears to be no advantage to ADT where the Gleason score is 6 or less and PSA is 15 or less. ADT is beneficial in patients treated to standard dose radiation with Gleason 6 disease and a PSA greater than 15 or where the Gleason score is 7 or higher.

OBJECTIVE: To update current evidence for prostate-specific antigen (PSA) screening for prostate cancer and to give readers some practical information to discuss with patients. QUALITY OF EVIDENCE A MEDLINE: search revealed only three randomized studies, two of which are incomplete. Several controlled non-randomized studies were found. MAIN MESSAGE: Two ongoing studies have not yet reported survival data, but have added to evidence for screening intervals. One Canadian randomized study has been criticized for its design and conclusions. Non-randomized studies suggest that screening effectively identifies serious cancers and leads to earlier diagnosis. Mortality from prostate cancer has been falling in most western countries since 1992. This cannot be explained by PSA screening, which would probably not produce survival benefit until at least 10 years after its unofficial introduction in about 1990. CONCLUSION: Indirect evidence suggests that all men older than 45 with at least a 10-year life expectancy should be informed of the potential benefits and drawbacks of PSA screening so they can make an informed decision on whether to have the test.

OBJECTIVE: To describe treatments for localized prostate cancer: surgery, external radiation therapy, and brachytherapy; watchful waiting might also be appropriate. Patients trying to decide about treatment ask family physicians for advice. This article sets out a framework to aid patients (and physicians) in the decision. QUALITY OF EVIDENCE: Only two randomized studies comparing different treatments were identified. Because of the paucity of level I or II evidence, suggestions in this review are largely based on expert opinion and consensus statements. MAIN MESSAGE Risk-grouping and nomograms are useful for assessing treatments and estimating outcomes of treatment. Where treatments are equivalent, decisions can be based on perception of toxicity and convenience. Effects on patients'lives and on sexual, urinary, and bowel function vary by treatment modality. CONCLUSION: Men with low-risk prostate cancer should decide on treatment based on their perception of how treatment will affect their lives. Men with higher-risk cancers might accept adverse effects on their quality of life in return for longer survival.

Context: Active surveillance (AS) is an important strategy to reduce prostate cancer overtreatment. However, the optimal criteria for eligibility and predictors of progression while on AS are debated. Objective: To review primary data on markers, genetic factors, and risk stratification for patient selection and predictors of progression during AS. Evidence acquisition: Electronic searches were conducted in PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to April 2014 for original articles on biomarkers and risk stratification for AS. Evidence synthesis: Patient factors associated with AS outcomes in some studies include age, race, and family history. Multiple studies provide consistent evidence that a lower percentage of free prostate-specific antigen (PSA), a higher Prostate Health Index (PHI), a higher PSA density (PSAD), and greater biopsy core involvement at baseline predict a greater risk of progression. During follow-up, serial measurements of PHI and PSAD, as well as repeat biopsy results, predict later biopsy progression. While some studies have suggested a univariate relationship between urinary prostate cancer antigen 3 (PCA3) and transmembrane protease, serine 2-v-ets avian erythroblastosis virus E26 oncogene homolog gene fusion (TMPRSS2:ERG) with adverse biopsy features, these markers have not been consistently shown to independently predict AS outcomes. No conclusive data support the use of genetic tests in AS. Limitations of these studies include heterogeneous definitions of progression and limited follow-up. Conclusions: There is a growing body of literature on patient characteristics, biopsy features, and biomarkers with potential utility in AS. More data are needed on practical applications such as combining these tests into multivariable clinical algorithms and long-term outcomes to further improve AS in the future. Patient summary: Several PSA-based tests (free PSA, PHI, PSAD) and the extent of cancer on biopsy can help to stratify the risk of progression during active surveillance. Investigation of several other markers is under way. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.