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

En el umbral de la era interespiritual

Poco a poco se va cobrando conciencia de que estamos llegando al final de la civilización que hemos conocido durante siglos. La primera época axial (desde el 1.000 A.C. hasta Jesús y Mahoma) vió la formación de la base espiritual de la cultura, con sus sabios fundadores: los místicos de India que inspiraron los Vedas y Upanishads, Zoroastro en Persia, Confucio en China, los profetas Elías, Isaías y Jeremías en Israel, Sócrates, Platón y Aristóteles en Grecia, hasta Jesús y Mahoma. Ahora surgen nuevas exigencias. Esa primera época fue demasiado excluyente por lo que se refiere a las religiones, que crecieron relativamente aisladas las unas de las otras. En nuestros días, con las telecomunicaciones y los viajes, este aislamiento ya no es posible. Una civilización dominada por una o dos culturas ha dejado de ser posible y deseable. Estamos en el umbral de una segunda época axial, que se caracterizará por un sentido profundo de comunidad entre las religiones y, consiguientemente, por una sabiduría ínterespiritual y un compromiso profundo para con la justicia medioambiental. La segunda época axial será, pues, interespiritual y, también, ecológica, términos intercambiables, pues esta segunda época sugiere dos cambios que se implican mutuamente: la emergencia de la sabiduría interespiritual, a partir del descubrimiento de la comunidad entre miembros de religiones distintas, y la atención al valor último de —y a la inquietud por— la Tierra. Una sabiduría interespiritual incluye una ecoespiritualidad sana, que es una nueva forma de misticismo de la naturaleza. Quisiera explorar estas intuiciones y sugerir que requieren una comprensión multiconfesional de una espiritualidad que, siendo universal, al mismo tiempo preserva su rica diversidad. Esta espiritualidad global o multiconfesional es la base para que se pueda hablar de sabiduría interespiritual. Se desarrollarán los elementos de una concepción de este tipo y se subrayarán sus posibilidades. Todo lo anterior se orienta esencialmente a la fundamentación más profunda de la cultura de la paz y a cómo las religiones, por supuesto en cuanto tales, pueden contribuir a ella. Es necesario ponderar atentamente la naturaleza, el papel y el alcance de la espiritualidad tal como funciona en un contexto global, contribuyendo a cambios sustanciales, como por ej.: al abandono de las instituciones de la guerra y, en definitiva, de toda forma de violencia

TOWARDS A CHRISTIAN VEDANTA: THE ENCOUNTER OF HINDUISM AND CHRISTIANITY ACCORDING TO BEDE GRIFFITHS

Bede Griffiths has sought for many years to formulate and express the relationship of the Christian and Hindu faiths. And he has done this within the context of a historical movement which is identified as sannyasic monasticism. In this study, the author attempts to discover how these two traditions are relatable and what precisely the terms of the relationship are in Bede Griffiths\u27 understanding. In order to answer these questions, the author considers Bede\u27s views on knowledge, metaphysical reality and his mystical or contemplative theology, for the nature of knowledge is answered in Bede\u27s version of the perennial philosophy which itself rests on spiritual wisdom or contemplative awareness. The author then examines the main themes of Bede\u27s theology, and considers the primordial link between the Judeo-Christian tradition and Hinduism in Bede\u27s notion of the Cosmic Revelation/Covenant which unites them in an original, pure experience of the Divine in nature and in the depths of the soul. Thus the first indication of relatability is discovered. Hinduism is shown to be a religion of the Cosmic Revelation/Covenant in which all traditions share. The author then explores the terms of the relationship on the more ultimate level of both traditions, as Bede regards them: advaita/saccidananda and the Trinity. He finds that Bede understands the Trinity as a deeper grasp of the mystery because of the note of interpersonal relationship, which is one of communion in knowledge and love. The author shows how Bede relates saccidananda and Trinity in the same ontological mystery of ultimate depth, but does not identify them, or equate them. Furthermore, it is also shown hows accidananda, in Bede\u27s view, can be a term for the Trinity in an Indian Christian theology which is also a Christian form of the Vedanta, though it is not itself the Trinity in its Hindu meaning. It can, however, be appropriated as a term for the Trinity. The author goes on to examine Bede\u27s Christology, his notions of Christian Tantrism, Christian sannyasa and his vision of the Church\u27s role as the unifying center of the world\u27s religions. Arising out of this study of Bede Griffiths\u27 contemplative, dialogical theology, the author identifies three creative implications: existential convergence, the ontological continuum/spiral, and a new model of the Church