Background

Prostate cancer (PC) is the most common cancer in men in the UK. Radiotherapy (RT) is a recognised treatment for PC and high-dose conformal radiotherapy (CRT) is the recommended standard of care for localised or locally advanced tumours. Intensity-modulated radiotherapy (IMRT) allows better dose distributions in RT.

Objectives

This report evaluates the clinical effectiveness and cost-effectiveness of IMRT for the radical treatment of PC.

Methods

A systematic literature review of the clinical effectiveness and cost-effectiveness of IMRT in PC was conducted. Comparators were three-dimensional conformal radiotherapy (3DCRT) or radical prostatectomy. Outcomes sought were overall survival, biochemical [prostate-specific antigen (PSA)] relapse-free survival, toxicity and health-related quality of life (HRQoL). Fifteen electronic bibliographic databases were searched (including MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), MEDLINE In-Process & Other Non-Indexed Citations, etc.) in January 2009 and updated in May 2009, and the reference lists of relevant articles were checked. Studies only published in languages other than English were excluded.

An economic model was developed to examine the cost-effectiveness of IMRT in comparison to 3DCRT. Four scenarios were modelled based on the studies which reported both PSA survival and late gastrointestinal (GI) toxicity. In two scenarios equal PSA survival was assumed for IMRT and 3DCRT, the other two having greater PSA survival for the IMRT cohort. As there was very limited data on clinical outcomes, the model estimates progression to clinical failure and PC death from the surrogate outcome of PSA failure.

Results

No randomised controlled trials (RCTs) of IMRT versus 3DCRT in PC were available, but 13 non-randomised studies comparing IMRT with 3DCRT were found, of which five were only available as abstracts. One abstract reported overall survival. Biochemical relapse-free survival was not affected by treatment group, except where there was a dose difference between groups, in which case higher dose IMRT was favoured over lower dose 3DCRT. Most studies reported an advantage for IMRT in GI toxicity, attributed to increased conformality of treatment compared with 3DCRT, particularly with regard to volume of rectum treated. There was some indication that genitourinary (GU) toxicity was worse for patients treated with dose-escalated IMRT, although most studies did not find a significant treatment effect. HRQoL improved for both treatment groups following RT, with any group difference resolved by 6 months after treatment. No comparative studies of IMRT versus prostatectomy were identified. No comparative studies of IMRT in PC patients with bone metastasis were identified.

Discussion

A comprehensive, systematic literature review was undertaken, but the strength of the conclusions of this review are limited by the lack of RCTs, and any comparative studies for some patient groups. The comparative data of IMRT versus 3DCRT seem to support the theory that higher doses, up to 81 Gy, can improve biochemical survival for patients with localised PC, concurring with data on CRT. The data also suggest that toxicity can be reduced by increasing conformality of treatment, particularly with regard to GI toxicity, which can be more easily achieved with IMRT than 3DCRT. Whether differences in GI toxicity between IMRT and 3DCRT are sufficient for IMRT to be cost-effective is uncertain, depending on the difference in incidence of GI toxicity, its duration and the cost difference between IMRT and 3DCRT.

Conclusions

Publication

• Hummel S, Simpson EL, Hemingway P, Stevenson MD, Rees A Intensity-modulated radiotherapy for the treatment of prostate cancer: a systematic review and economic evaluation. Health Technol Assess 2010;14(47). [PubMed: 21029717]

NIHR Health Technology Assessment programme

The Health Technology Assessment (HTA) programme, part of the National Institute for Health Research (NIHR), was set up in 1993. It produces high-quality research information on the effectiveness, costs and broader impact of health technologies for those who use, manage and provide care in the NHS. ‘Health technologies’ are broadly defined as all interventions used to promote health, prevent and treat disease, and improve rehabilitation and long-term care.

The research findings from the HTA programme directly influence decision-making bodies such as the National Institute for Health and Clinical Excellence (NICE) and the National Screening Committee (NSC). HTA findings also help to improve the quality of clinical practice in the NHS indirectly in that they form a key component of the ‘National Knowledge Service’.

The HTA programme is needs led in that it fills gaps in the evidence needed by the NHS. There are three routes to the start of projects.

First is the commissioned route. Suggestions for research are actively sought from people working in the NHS, from the public and consumer groups and from professional bodies such as royal colleges and NHS trusts. These suggestions are carefully prioritised by panels of independent experts (including NHS service users). The HTA programme then commissions the research by competitive tender.

Second, the HTA programme provides grants for clinical trials for researchers who identify research questions. These are assessed for importance to patients and the NHS, and scientific rigour.

Third, through its Technology Assessment Report (TAR) call-off contract, the HTA programme commissions bespoke reports, principally for NICE, but also for other policy-makers. TARs bring together evidence on the value of specific technologies.

Some HTA research projects, including TARs, may take only months, others need several years. They can cost from as little as £40,000 to over £1 million, and may involve synthesising existing evidence, undertaking a trial, or other research collecting new data to answer a research problem.

The final reports from HTA projects are peer reviewed by a number of independent expert referees before publication in the widely read journal series Health Technology Assessment.

Criteria for inclusion in the HTA journal series

Reports are published in the HTA journal series if (1) they have resulted from work for the HTA programme, and (2) they are of a sufficiently high scientific quality as assessed by the referees and editors.

Reviews in Health Technology Assessment are termed ‘systematic’ when the account of the search, appraisal and synthesis methods (to minimise biases and random errors) would, in theory, permit the replication of the review by others.

The research reported in this issue of the journal was commissioned by the HTA programme as project number 08/227/01. The contractual start date was in December 2008. The draft report began editorial review in November 2009 and was accepted for publication in March 2010. As the funder, by devising a commissioning brief, the HTA programme specified the research question and study design. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the referees for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.

The views expressed in this publication are those of the authors and not necessarily those of the HTA programme or the Department of Health.

Editor-in-Chief: Professor Tom Walley CBE

Series Editors: Dr Martin Ashton-Key, Professor Aileen Clarke, Professor Chris Hyde, Dr Tom Marshall, Dr John Powell, Dr Rob Riemsma and Professor Ken Stein