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Adding radiotherapy directed at the prostate to hormone treatment for all men with metastatic prostate cancer makes no difference to overall survival. However, when men with a limited number of metastases confined to the bones of the pelvis and spine are treated with radiotherapy to the prostate, their survival improves.
The standard treatment for men with metastatic prostate cancer is anti-androgen hormone therapy, and this is sometimes combined with chemotherapy. Radiotherapy of the prostate itself is only usually used for symptom relief.
This NIHR part-funded trial compared the effects of standard care with or without radiotherapy to the prostate on overall survival for over 2,000 men. It found that radiotherapy improved three-year survival rate from 73 to 81% in men with a limited number of metastases confined to the spine and pelvis. In this group, it also prevented any disease progression over three years in half of them compared to a third on standard care.
This well-conducted multicentre trial supports the use of radiotherapy for this select group of men with limited metastases.
Why was this study needed?
Prostate cancer is the most common cancer in UK men, with around 47,200 new cases each year. Around 4 in 10 cases in England and Northern Ireland and 6 in 10 cases in Scotland are diagnosed at a late stage when the disease has already spread. At this point, hormone treatment is currently recommended to prevent androgens in the body promoting tumour growth, alongside other chemotherapy drugs. In this situation, radiotherapy to the prostate is only given to provide symptom relief.
Recently, the results of some studies have suggested that radiotherapy to the original tumour site might have additional benefits. A previous trial of 432 men suggested that those with fewer than five secondary bone tumours had better survival when radiotherapy was added to hormone therapy. This randomised controlled trial set out to provide further evidence for this.
What did this study do?
STAMPEDE was a randomised controlled trial that took place in 117 hospitals in Switzerland and the UK. A total of 2,061 men with newly diagnosed prostate cancer with metastases, confirmed on a bone scan, took part.
Participants were randomised to either standard care (lifelong anti-androgen hormone therapy, with or without chemotherapy using docetaxel) or standard care plus radiotherapy to the prostate.
This was a large study that was well-powered to detect effects on overall survival. There were also adequate numbers of men in each subgroup to determine the effect on men with low and high metastatic burden, defined according to how far the metastases had spread.
What did it find?
After three years:
- There was no difference in overall survival between men who had radiotherapy with standard care compared with those who just had standard care (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.80 to 1.06). After an average follow-up of 37 months, 370 men in the radiotherapy group had died (three-year survival 65%) compared to 391 men in the control group (three-year survival 62%).
- In men with lower metastatic burden (metastases to either the local lymph nodes or the bones in the pelvis or spine) radiotherapy improved three-year survival rate, 81% versus 73% of those on standard care (HR 0.68, 95% CI 0.52 to 0.90).
- By contrast, in men with a high metastatic burden (four or more bone metastases with one or more outside the spine or pelvis, or metastases to other organs, or both) the addition of radiotherapy had no benefit on survival, 53% versus 54% on standard care (HR 1.07, 95% CI 0.90 to 1.28).
- Overall failure-free survival (the proportion of people who did not have a rise in PSA or progression of disease) was increased by radiotherapy, with 32% having no progression compared to 22% with standard care (HR 0.76, 95% CI 0.68 to 0.84).
- The failure-free survival difference was mostly due to people with low metastatic burden, with 50% having no progression on radiotherapy compared to 33% on standard care (HR 0.59, 95% CI 0.49 to 0.72). There was no difference for people with high metastatic burden, 18% versus 17% (HR 0.88, 95% CI 0.77 to 1.01).
What does current guidance say on this issue?
NICE guidelines from 2014 recommend that all men with metastatic prostate cancer are offered a bilateral orchidectomy (removal of both testicles) as an alternative to androgen-blocking hormonal treatments.
There is no recommendation regarding radiotherapy in men with metastatic prostate cancer.
What are the implications?
This study adds further evidence that radiotherapy could benefit men with newly diagnosed prostate cancer with local metastases. The trial used CT and bone scans to define low and high metastatic burden. PET scans, which can detect smaller cancer deposits, are becoming widely available and may allocate people differently. However, the researchers did perform further analysis using different definitions of ‘low metastatic burden', with similar positive results. They are now planning to refine the definition to be more clinically useful.
Nevertheless, radiotherapy can now be considered as a potential add-on treatment in men without advanced metastases, but the optimal dose and schedule still needs to be determined.
Citation and Funding
Parker CC, James ND, Brawley CD et al; Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet. 2018;392:2353-66.
Funded by Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Astellas, Clovis Oncology, Janssen, Novartis, Pfizer and Sanofi-Aventis. This project was part-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at the Royal Marsden NHS Foundation Trust.
Bibliography
Boeri L, Sharma, V, Karnes, RJ. Radiotherapy for newly diagnosed oligometastatic prostate cancer. Lancet. 2018;392:2327-28.
Boevé LMS, Hulshof MCCM, Vis AN et al. Effect on survival of androgen deprivation therapy alone compared to androgen deprivation therapy combined with concurrent radiation therapy to the prostate in patients with primary bone metastatic prostate cancer in a prospective randomised clinical trial: data from the HORRAD Trial. Eur Urol. 2018; Sep 25. doi: 10.1016/j.eururo.2018.09.008. [Epub ahead of print].
Cancer Research UK. Prostate cancer statistics. London: Cancer Research UK; accessed January 2019.
NICE. Prostate cancer: diagnosis and management. CG175. London: National Institute for Health and Care Excellence. 2014.
Parker CC, James ND, Brawley CD et al. Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial. PLoS Medicine. 2022;19:6.
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