Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

'Patient' voices, social movements and the habitus; how psychiatric survivors 'speak out'

What is the 'voice' of the mental health 'user'? This paper seeks to address this question through the presentation of a detailed comparative analysis of two anthologies written by people living with mental 'illness' in the 1950s and 1990s. Using a narrative-style qualitative analysis, the structure and content of the two anthologies is explored. The analysis illustrates the way in which the 'voice' of the mental patient in the 1950s was very different to that of today. The paper then aims to provide a theoretical explanation that accounts for this transformation of voice. Appropriating theoretical concepts from phenomenology and sociology, in particular, Bourdieu's concept of 'habitus', the paper explores the way in which the 'personal' voice of the mental patient is formulated in dialogical relation to wider public and collective movements. These, in turn, connect to broader transformations in the social, economic and health 'fields'.Mental health Psychiatric patient Voice Habitus Social movements

'Let me explain': narrative emplotment and one patient's experience of oral cancer

Recent research has investigated the way in which serious illness potentially poses a threat to peoples' sense of ontological security by throwing into doubt assumptions about time and the future. One of the main ways in which people adjust to such threats is through the use of narrative (either consciously or unconsciously) which helps to make sense of illness. Of particular relevance to people learning to live with a cancer diagnosis, is the concept of 'therapeutic emplotment' developed by Del Vecchio Good et al. (1994). This concept refers to the way in which oncologists are taught to structure temporal horizons for their patients in a particular way in order to instill and maintain hope in the context of arduous and toxic treatments. Using a case-study of one man's process of adapting to oral cancer (John Diamond's posthumously published serialised diary entries in The Times), this paper investigates the way in which such 'therapeutic emplotment' is implicitly incorporated by the patient, providing an underlying plot structure to his story. Following Diamond's diary entries over the 4 years duration of his illness, this paper analytically divides them into six main stages, documenting the underlying temporal structure and themes accompanying each stage of adaptation. The paper illustrates the way in which 'therapeutic emplotment' encourages the patient to focus on the immediate present and to place faith in the efficacy of specific treatments. However, it also explores how the attempt to live in the context of such a plot is fraught with anxiety for the patient, and how it co-exists with other largely 'unspoken narratives' of uncertainty, fear and skepticism in relation to the power of medicine. The main aim of the paper is to document, for the first time, the process of 'therapeutic emplotment' from the oral cancer patient's point of view.Oral cancer Narrative Plot Therapeutic emplotment Time Adaptation to illness

Stories of illness and trauma survival: liberation or repression?

This paper aims to expand upon recent research addressing the relationship between power and cultural stories of illness. It does this by exploring the stories of 'healing' and 'survival' produced by people who have undergone traumatic experiences such as childhood sexual abuse and a HIV positive diagnosis. The liberating and/or repressive potential of cultural stories of illness are defined in accordance with their capacity to produce 'minimal' or more 'reflective' selves, as characterised by Lasch [Lasch, C., 1985. The Minimal Self. Picador, London.] and Giddens [Giddens, A., 1991. Modernity and Self-identity: Self and Society in the Later Modern Age. Polity Press, Cambridge.], respectively. Two predominant stories of survival are identified in this paper: the 'healing' story and the 'normalising' story. Each of these are explored in an attempt to address the question: How do we distinguish between 'liberating' and 'repressing' technologies of the self with regard to the telling of illness stories? [Frank, A., 1998. Stories of illness as care of the self: a Foucauldian dialogue. Health 2(3), 329-348, forthcoming.]. Through an examination of survivors' attempts to overcome their traumatic experiences via the appropriation of various illness stories, it is concluded that this question can only be answered in the practical and social context of each individual's life.Narrative Childhood sexual abuse HIV/AIDS Survival