http://oncology.thelancet.com Vol 8 June 2007 475 Articles Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomised controlled trial David P Dearnaley, Matthew R Sydes, John D Graham, Edwin G Aird, David Bottomley, Richard A Cowan, Robert A Huddart, Chakiath C Jose, John HL Matthews, Jeremy Millar, A Rollo Moore, Rachel C Morgan, J Martin Russell, Christopher D Scrase, Richard J Stephens, Isabel Syndikus, Mahesh KB Parmar, on behalf of the RT01 collaborators Summary Background In men with localised prostate cancer, conformal radiotherapy (CFRT) could deliver higher doses of radiation than does standard-dose conventional radical external-beam radiotherapy, and could improve long-term efficacy, potentially at the cost of increased toxicity. We aimed to present the first analyses of effectiveness from the MRC RT01 randomised controlled trial. Methods The MRC RT01 trial included 843 men with localised prostate cancer who were randomly assigned to standard-dose CFRT or escalated-dose CFRT, both administered with neoadjuvant androgen suppression. Primary endpoints were biochemical-progression-free survival (bPFS), freedom from local progression, metastases-free survival, overall survival, and late toxicity scores. The toxicity scores were measured with questionnaires for physicians and patients that included the Radiation Therapy Oncology Group (RTOG), the Late Effects on Normal Tissue: Subjective/Objective/Management (LENT/SOM) scales, and the University of California, Los Angeles Prostate Cancer Index (UCLA PCI) scales. Analysis was done by intention to treat. This trial is registered at the Current Controlled Trials website http://www.controlled-trials.com/ISRCTN47772397. Findings Between January, 1998, and December, 2002, 843 men were randomly assigned to escalated-dose CFRT (n=422) or standard-dose CFRT (n=421). In the escalated group, the hazard ratio (HR) for bPFS was 0·67 (95% CI 0·53–0·85, p=0·0007). We noted 71% bPFS (108 cumulative events) and 60% bPFS (149 cumulative events) by 5 years in the escalated and standard groups, respectively. HR for clinical progression-free survival was 0·69 (0·47–1·02; p=0·064); local control was 0·65 (0·36–1·18; p=0·16); freedom from salvage androgen suppression was 0·78 (0·57–1·07; p=0·12); and metastases-free survival was 0·74 (0·47–1·18; p=0·21). HR for late bowel toxicity in the escalated group was 1·47 (1·12–1·92) according to the RTOG (grade ≥2) scale; 1·44 (1·16–1·80) according to the LENT/SOM (grade ≥2) scales; and 1·28 (1·03–1·60) according to the UCLA PCI (score ≥30) scale. 33% of the escalated and 24% of the standard group reported late bowel toxicity within 5 years of starting treatment. HR for late bladder toxicity according to the RTOG (grade ≥2) scale was 1·36 (0·90–2·06), but this finding was not supported by the LENT/SOM (grade ≥2) scales (HR 1·07 [0·90–1·29]), nor the UCLA PCI (score ≥30) scale (HR 1·05 [0·81–1·36]). Interpretation Escalated-dose CFRT with neoadjuvant androgen suppression seems clinically worthwhile in terms of bPFS, progression-free survival, and decreased use of salvage androgen suppression. This additional efficacy is offset by an increased incidence of longer term adverse events. Introduction Prostate cancer is now the most commonly diagnosed cancer in men in the UK, USA, and western Europe; in 2000, the global estimate of deaths per year was 263 000. 1 The introduction of PSA testing has led to an increasing proportion of patients presenting with localised disease. Management options are controversial and include radical prostatectomy, external-beam radiotherapy, brachytherapy, and active surveillance or monitoring of men with favourable prognostic factors 2 or, alternatively, watchful waiting for those who are unsuitable for a radical curative treatment approach. External-beam radiotherapy might be most appropriate for men with intermediate-risk or high-risk features, 3–5 and is associated with long-term disease control in most men with prostate cancer. 6 Advances in radiation technology have enabled more precise and accurate treatment that allows the delivery of higher radiation doses and improved disease control while maintaining an acceptable frequency of side-effects. Conventional radical external-beam radiotherapy is limited to doses of 64–70 Gy in 1·8–2·0 Gy fractions because of the risk of long-term toxic effects to the bladder and rectum. Within 5 years of being treated with this type of radiotherapy, up to 33% of patients will have relapsed (either clinically or biochemically, ie, increasing prostate serum antigen [PSA] concentrations) or died. 7 Conformal radiotherapy (CFRT) techniques use linear accelerators with multileaf collimators or customised shaped blocks to shape the radiotherapy beam. Due to Lancet Oncol 2007; 8: 475–87 Published Online May 4, 2007 DOI:10.1016/S1470- 2045(07)70143-2 See Reflection and Reaction page 459 Institute of Cancer Research and Royal Marsden Hospitals, Sutton and London, UK (D P Dearnaley FRCR, R A Huddart FRCR, A R Moore MSc); Cancer Group, MRC Clinical Trials Unit, London, UK (R C Morgan MSc, M K B Parmar DPhil, R J Stephens, M R Sydes CStat); Clatterbridge Centre for Oncology, Wirral, UK (I Syndikus FRCR); Auckland Hospital, Auckland, New Zealand (J H L Matthews FRACR, C C Jose FRACR); Ipswich Hospital, Ipswich, UK (C D Scrase FRCR); Christie Hospital, Manchester, UK (R A Cowan FRCR); Beatson Oncology Centre, Western Infirmary, Glasgow, UK (J D Graham FRCR, J M Russell FRCR); Mount Vernon Hospital, Northwood, UK (E G Aird PhD); Alfred Hospital, Melbourne, VIC, Australia (J Millar FRACR); Cookridge Hospital, Leeds, UK (D Bottomley FRCR); and Bristol Haematology and Oncology Centre, Bristol, UK (J D Graham) Correspondence to: Dr David Dearnaley, Institute of Cancer Research and Royal Marsden Hospitals, Sutton, Surrey, SM5 2PT, UK rt01@ctu.mrc.ac.uk