New prostate cancer Tx will save millions

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A shorter course of prostate cancer radiotherapy, involving fewer hospital visits and higher individual doses of radiotherapy, is as effective as the current standard treatment for both survival and quality of life, a major UK study reports.

Researchers leading the 14-year trial believe the new treatment schedule would be more convenient for patients and could save the UK’s National Health Service (NHS) tens of millions of pounds per year.

The study, led by a team at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, found benefits for a 20-dose course of a modern type of radiotherapy over a 37-dose course, which is the current NHS standard. The researchers said the findings of their study, which was funded by Cancer Research UK, supported a change in clinical practice for prostate cancer radiotherapy with the 20-dose schedule becoming the new standard.

Similar trials from the same research group – led by the ICR and The Royal Marsden, and including more than 70 UK centres – proved the benefits of fewer, higher doses of radiation in breast cancer, and helped set NICE guidance that has saved the NHS around £50m a year since 2009.

The new regime for prostate cancer would save 17 hospital trips and complex radiotherapy treatments for each patient, leading to a reduction nationally of more than 150,000 visits per year.

The trial followed more than 3,200 men being treated for prostate cancer between 2002 and 2011 at more than 70 research centres across the UK. It compared the standard radiotherapy schedule of 37 doses of 2 Grays per day with two other regimes – one delivering 19 doses of 3 Gray per day, and the other 20 doses of 3 Gray per day.

The results showed that after five years the 20-dose schedule was not inferior to the 37-dose schedule for treatment effectiveness or quality of life. The trial also showed that treatment with fewer, higher doses of intensity-modulated radiotherapy was associated with less than half the rate of side-effects of older conformal radiotherapy.

The trial has already introduced modern quality-assured ‘intensity-modulated’ radiotherapy for prostate cancer to dozens of research centres across the UK.

Lead investigator Professor David Dearnaley, professor of uro-oncology at the ICR and consultant clinical oncologist at The Royal Marsden, said: “Our study shows that fewer, larger doses of intensity-modulated radiotherapy work just as well as more, smaller doses for men with prostate cancer, without reducing quality of life — and would save each man the inconvenience of 17 more hospital visits.

“If the new regime is incorporated into routine clinical practice, it will save the NHS tens of millions of pounds per year as well as freeing up space for other patients to have radiotherapy more quickly.”

Study co-leader Dr Emma Hall, deputy director of the Cancer Research UK-funded clinical trials and statistics unit at the ICR, which coordinated the study, said: “Our trial showed this modern radiotherapy is as effective when used over 20 days as over 37 days, the present standard regime. Our results also show that using state-of-the art radiotherapy methods significantly reduces the treatment side effects that matter to patients.

“We already know many centres have already switched to the new regime, and we hope it will soon become the new standard of care for prostate cancer treatment on the NHS.”

Professor Paul Workman, CEO of the ICR, said: “This is an important study which opens the door to better, more convenient care for patients while saving the NHS valuable money that can be spent on other treatments. Our researchers have a strong track record not only of developing improved forms of radiotherapy but also in running major clinical trials like this that can deliver changes in routine clinical practice.”

Summary
Background
Prostate cancer might have high radiation-fraction sensitivity that would give a therapeutic advantage to hypofractionated treatment. We present a pre-planned analysis of the efficacy and side-effects of a randomised trial comparing conventional and hypofractionated radiotherapy after 5 years follow-up.
Methods
CHHiP is a randomised, phase 3, non-inferiority trial that recruited men with localised prostate cancer (pT1b–T3aN0M0). Patients were randomly assigned (1:1:1) to conventional (74 Gy delivered in 37 fractions over 7•4 weeks) or one of two hypofractionated schedules (60 Gy in 20 fractions over 4 weeks or 57 Gy in 19 fractions over 3•8 weeks) all delivered with intensity-modulated techniques. Most patients were given radiotherapy with 3–6 months of neoadjuvant and concurrent androgen suppression. Randomisation was by computer-generated random permuted blocks, stratified by National Comprehensive Cancer Network (NCCN) risk group and radiotherapy treatment centre, and treatment allocation was not masked. The primary endpoint was time to biochemical or clinical failure; the critical hazard ratio (HR) for non-inferiority was 1•208. Analysis was by intention to treat. Long-term follow-up continues. The CHHiP trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN97182923.
Findings
Between Oct 18, 2002, and June 17, 2011, 3216 men were enrolled from 71 centres and randomly assigned (74 Gy group, 1065 patients; 60 Gy group, 1074 patients; 57 Gy group, 1077 patients). Median follow-up was 62•4 months (IQR 53•9–77•0). The proportion of patients who were biochemical or clinical failure free at 5 years was 88•3% (95% CI 86•0–90•2) in the 74 Gy group, 90•6% (88•5–92•3) in the 60 Gy group, and 85•9% (83•4–88•0) in the 57 Gy group. 60 Gy was non-inferior to 74 Gy (HR 0•84 [90% CI 0•68–1•03], pNI=0•0018) but non-inferiority could not be claimed for 57 Gy compared with 74 Gy (HR 1•20 [0•99–1•46], pNI=0•48). Long-term side-effects were similar in the hypofractionated groups compared with the conventional group. There were no significant differences in either the proportion or cumulative incidence of side-effects 5 years after treatment using three clinician-reported as well as patient-reported outcome measures. The estimated cumulative 5 year incidence of Radiation Therapy Oncology Group (RTOG) grade 2 or worse bowel and bladder adverse events was 13•7% (111 events) and 9•1% (66 events) in the 74 Gy group, 11•9% (105 events) and 11•7% (88 events) in the 60 Gy group, 11•3% (95 events) and 6•6% (57 events) in the 57 Gy group, respectively. No treatment-related deaths were reported.
Interpretation
Hypofractionated radiotherapy using 60 Gy in 20 fractions is non-inferior to conventional fractionation using 74 Gy in 37 fractions and is recommended as a new standard of care for external-beam radiotherapy of localised prostate cancer.

Authors
Prof David Dearnaley, Isabel Syndikus, Helen Mossop, Vincent Khoo, Alison Birtle, David Bloomfield, John Graham, Peter Kirkbride, John Logue, Zafar Malik, Julian Money-Kyrle, Prof Joe M O’Sullivan, Miguel Panades, Chris Parker, Helen Patterson, Christopher Scrase, John Staffurth, Andrew Stockdale, Jean Tremlett, Margaret Bidmead, Helen Mayles, Olivia Naismith, Chris South, Annie Gao, Clare Cruickshank, Shama Hassan, Julia Pugh, Clare Griffin, Emma Hall

Institute of Cancer Research material
The Lancet Oncology article summary


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