Bone Metastatic Burden and Survival Outcomes With Prostate Radiotherapy for Newly Diagnosed Metastatic Disease

Analysis From the STAMPEDE Trial

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In an analysis from the STAMPEDE trial reported in JAMA Oncology, Ali et al found that a lower number of bone metastases was associated with improved overall and failure-free survival in patients receiving prostate radiotherapy for newly diagnosed M1 metastatic prostate cancer.

Study Details

The exploratory analysis involved data from 1,939 men (of 2,061) in the STAMPEDE trial who were randomly assigned to prostate radiotherapy plus standard of care (androgen-deprivation therapy with or without docetaxel; n = 963) vs standard of care alone (n = 976). Treatment outcomes were assessed based on metastatic site and extent as determined by conventional imaging with computed tomography/magnetic resonance imaging and bone scans.

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Key Findings

Among all patients included in the analysis, 1,587 (82%) had bone metastases with or without additional nonregional lymph node metastasis, 181 (9%) had only nonregional lymph node metastasis (M1a), and 171 (9%) had visceral/other metastasis. Median follow-up was 37 months (interquartile range = 24–48 months). Overall, lower bone metastasis counts were associated with overall and failure-free survival benefit from prostate radiotherapy vs standard of care alone.

For overall survival, benefit from radiotherapy decreased continuously as number of bone metastases increased, with benefit being the greatest at up to three metastases; thereafter, benefit decreased continuously, with plotting of estimated treatment effect showing that the point estimate crossed the line of equivalence at eight bone metastases. Absolute improvements in 3-year overall survival vs standard of care were 8.5%, 6.2%, and 5.8% with one, two, and three metastases, respectively.

For failure-free survival, radiotherapy was associated with absolute improvements vs standard of care of 21.5%, 10.1%, 14.2%, and 8.84% in 3-year rates with one, two, three, and four bone metastases. The line of equivalence was crossed at approximately nine metastases.

Subgroup analyses showed that the magnitude of benefit associated with radiotherapy was greater in patients with low metastatic burden with only nonregional lymph nodes (M1a) or three or fewer bone metastases without visceral metastasis (hazard ratio [HR] for overall survival = 0.62, 95% confidence interval [CI] = 0.46–0.83; HR for failure-free survival = 0.57, 95% CI = 0.47–0.70) vs patients with four or more bone metastases or any visceral/other metastasis (HR for overall survival = 1.08, 95% CI = 0.91–1.28; P = .003 for interaction; HR for failure-free survival = 0.87, 95% CI = 0.76–0.99; P = .002 for interaction).

The investigators concluded, “In this exploratory analysis of a randomized clinical trial, bone metastasis count and metastasis location based on conventional imaging were associated with overall survival and failure-free survival benefit from prostate radiotherapy in M1 disease.”

They noted, “We have used a systematic approach herein to consolidate the notion that bone metastasis number based on conventional bone scan is predictive of survival benefit from adding prostate radiotherapy to standard of care in newly diagnosed metastatic prostate cancer. This benefit is most pronounced up to three bone metastases; at or below this, there is good evidence that the addition of prostate radiotherapy to standard of care systemic therapy improves overall survival and failure-free survival in these men. We also present evidence that men with M1a disease have improved failure-free survival.”

Noel W. Clarke, MBBS, ChM, of the Department of Surgery, The Christie NHS Foundation Trust, Manchester, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was funded by Cancer Research UK, Medical Research Council, Astellas, Clovis Oncology, Janssen, Novartis, Pfizer, and Sanofi Aventis. For full disclosures of the study authors, visit

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