Radiotherapy benefits some men whose prostate cancer has spread to their bones

NIHR | January 2019 | Radiotherapy benefits some men whose prostate cancer has spread to their bones

An NIHR Signal highlights a trial part-funded by NIHR, published in October 2018, which compared the effects of standard care with or without radiotherapy to the prostate on overall survival for over 2000 men.  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.

The trial 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.

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STAMPEDE was a randomised controlled trial  that took place in more than 100 hospitals in Switzerland and the UK. Over 2,000 men with newly diagnosed prostate cancer with metastases, confirmed on a bone scan, were recruited to the study.

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 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.

Treating the primary once the cancer has metastasised has conventionally thought to be futile. This has been challenged by finding that in low metastatic burden prostate cancer, radiotherapy to the primary significantly improves survival and should become standard of care.

This study raises the issue whether this would apply to other cancers and interesting biological questions as to the mechanism. Is it an effect of debulking the primary?  Is it immunological?  Is it due to reducing secondary spread of aggressive clones?

It seems we have underestimated in prostate cancer, the impact of local control in the setting of metastatic disease

Professor Robert Huddart, Reader and Honorary Consultant, Royal Marsden NHS Foundation Trust 

(Source: NIHR)

NIHR Radiotherapy benefits some men whose prostate cancer has spread to their bones

 

 Parker, C.  et al | 2018| Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial|  The Lancet| 

 

Background
Based on previous findings, we hypothesised that radiotherapy to the prostate would improve overall survival in men with metastatic prostate cancer, and that the benefit would be greatest in patients with a low metastatic burden. We aimed to compare standard of care for metastatic prostate cancer, with and without radiotherapy.
Methods
We did a randomised controlled phase 3 trial at 117 hospitals in Switzerland and the UK. Eligible patients had newly diagnosed metastatic prostate cancer. We randomly allocated patients open-label in a 1:1 ratio to standard of care (control group) or standard of care and radiotherapy (radiotherapy group). Randomisation was stratified by hospital, age at randomisation, nodal involvement, WHO performance status, planned androgen deprivation therapy, planned docetaxel use (from December, 2015), and regular aspirin or non-steroidal anti-inflammatory drug use. Standard of care was lifelong androgen deprivation therapy, with up-front docetaxel permitted from December, 2015. Men allocated radiotherapy received either a daily (55 Gy in 20 fractions over 4 weeks) or weekly (36 Gy in six fractions over 6 weeks) schedule that was nominated before randomisation. The primary outcome was overall survival, measured as the number of deaths; this analysis had 90% power with a one-sided α of 2·5% for a hazard ratio (HR) of 0·75. Secondary outcomes were failure-free survival, progression-free survival, metastatic progression-free survival, prostate cancer-specific survival, and symptomatic local event-free survival. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. The primary outcome analysis was by intention to treat. Two prespecified subgroup analyses tested the effects of prostate radiotherapy by baseline metastatic burden and radiotherapy schedule.
Findings
Between Jan 22, 2013, and Sept 2, 2016, 2061 men underwent randomisation, 1029 were allocated the control and 1032 radiotherapy. Allocated groups were balanced, with a median age of 68 years (IQR 63–73) and median amount of prostate-specific antigen of 97 ng/mL (33–315). 367 (18%) patients received early docetaxel. 1082 (52%) participants nominated the daily radiotherapy schedule before randomisation and 979 (48%) the weekly schedule. 819 (40%) men had a low metastatic burden, 1120 (54%) had a high metastatic burden, and the metastatic burden was unknown for 122 (6%). Radiotherapy improved failure-free survival but not overall survival. Radiotherapy was well tolerated, with 48 (5%) adverse events (Radiation Therapy Oncology Group grade 3–4) reported during radiotherapy and 37 (4%) after radiotherapy. The proportion reporting at least one severe adverse event (Common Terminology Criteria for Adverse Events grade 3 or worse) was similar by treatment group in the safety population (398 [38%] with control and 380 [39%] with radiotherapy).
Interpretation
Radiotherapy to the prostate did not improve overall survival for unselected patients with newly diagnosed metastatic prostate cancer.

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