The early toxicity of escalated versus standard dose conformal radiotherapy with neo-adjuvant androgen suppression for patients with localised prostate cancer: Results from the MRC RT01 trial (ISRCTN47772397)

Dearnaley, David P.; Sydes, Matthew R.; Langley, Ruth E.; Graham, John D.; Huddart, Robert A.; Syndikus, Isabel; Matthews, John H.L.; Scrase, Christopher D.; Jose, Chakiath C.; Logue, John; Stephens, Richard J.; on behalf of the RT01 Collaborators,

doi:10.1016/j.radonc.2007.02.014

« Previous Next »Radiotherapy & Oncology
Volume 83, Issue 1 , Pages 31-41, April 2007

The early toxicity of escalated versus standard dose conformal radiotherapy with neo-adjuvant androgen suppression for patients with localised prostate cancer: Results from the MRC RT01 trial (ISRCTN47772397)☆

David P. Dearnaley
- Institute of Cancer Research and Royal Marsden Hospitals, Sutton, UK
- Corresponding author. D.P. Dearnaley, Institute of Cancer Research and Royal Marsden Hospitals, Sutton, Surrey SM5 2PT, United Kingdom.
Matthew R. Sydes
- Cancer Group, MRC Clinical Trials Unit, London, UK
Ruth E. Langley
- Cancer Group, MRC Clinical Trials Unit, London, UK
John D. Graham
- Beatson Oncology Centre, Western Infirmary, Glasgow, UK
- Bristol Haematology and Oncology Centre, Bristol Royal Infirmary, Bristol, United Kingdom (previously).
Robert A. Huddart
- Institute of Cancer Research and Royal Marsden Hospitals, Sutton, UK
Isabel Syndikus
- Clatterbridge Centre for Oncology, Wirral, UK
John H.L. Matthews
- Auckland Hospital, Auckland, New Zealand
Christopher D. Scrase
- Ipswich Hospital, Ipswich, UK
Chakiath C. Jose
- Auckland Hospital, Auckland, New Zealand
John Logue
- Christie Hospital, Manchester, UK
Richard J. Stephens
- Cancer Group, MRC Clinical Trials Unit, London, UK
on behalf of the RT01 Collaborators

Received 7 June 2006; received in revised form 7 February 2007; accepted 28 February 2007. published online 31 March 2007.

Abstract

Background

Five-year disease-free survival rates for localised prostate cancer following standard doses of conventional radical external beam radiotherapy are around 80%. Conformal radiotherapy (CFRT) raises the possibility that radiotherapy doses can be increased and long-term efficacy outcomes improved, with safety an important consideration.

Methods

MRC RT01 is a randomised controlled trial of 862 men with localised prostate cancer comparing Standard CFRT (64Gy/32f) versus Escalated CFRT (74Gy/37f), both administered with neo-adjuvant androgen suppression. Early toxicity was measured using physician-reported instruments (RTOG, LENT/SOM, Royal Marsden Scales) and patient-reported questionnaires (MOS SF-36, UCLA Prostate Cancer Index, FACT-P).

Results

Overall early radiotherapy toxicity was similar, apart from increased bladder, bowel and sexual toxicity, in the Escalated Group during a short immediate post-radiotherapy period. Toxicity in both groups had abated by week 12. Using RTOG Acute Toxicity scores, cumulative Grade ⩾2 bladder and bowel toxicity was 38% and 30% for Standard Group and 39% and 33% in Escalated Group, respectively. Urinary frequency (Royal Marsden Scale) improved in both groups from pre-androgen suppression to 6months post-radiotherapy (p<0.001), but bowel and sexual functioning deteriorated. This pattern was supported by patient-completed assessments. Six months after starting radiotherapy the incidence of RTOG Grade ⩾2 side-effects was low (<1%); but there were six reports of rectal ulceration (6 Escalated Group), six haematuria (5 Escalated Group) and eight urethral stricture (6 Escalated Group).

Conclusions

The two CFRT schedules with neo-adjuvant androgen suppression have broadly similar early toxicity profiles except for the immediate post-RT period. At 6months and compared to before hormone therapy, bladder symptoms improved, whereas bowel and sexual symptoms worsened. These assessments of early treatment safety will be complemented by further follow-up to document late side-effects and efficacy.

Keywords: Prostate cancer, Phase III trial, Conformal radiotherapy, Dose escalation, Radiation toxicity