Bone metastasis burden and metastasis location may be useful in predicting the survival benefit from prostate radiation therapy (RT) added to standard of care (SOC) for newly diagnosed metastatic prostate cancer (mPCa), according to a new study.

A secondary analysis of data from 1939 patients in the STAMPEDE trial demonstrated that overall survival (OS) and failure-free survival (FFS) achieved by adding prostate RT to SOC declined with increasing bone metastasis number, a team led by Noel W. Clarke, MBBS, ChM, of The Christie NHS Foundation Trust in Manchester, UK, reported in JAMA Oncology. The study also provides the first reported evidence that prostate RT added to SOC is associated with improved OS and FFS among those with only nonregional lymph node metastases.

For the study, investigators randomly assigned 963 men to receive prostate RT plus standard of care and 976 men to receive standard of care alone, respectively. They determined metastasis status using conventional computed tomography and bone scans. They defined failure-free survival as the time from randomization to the first of biochemical failure, progression locally, in lymph nodes, or in distant metastases, or death from PCa.

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The magnitude of benefit associated with the use of prostate RT along with SOC in terms of OS and FFS was greater among patients with only nonregional lymph node metastasis (M1a) or 3 or fewer bone metastases without visceral metastasis compared with patients who had 4 or more bone metastases or any visceral or other metastasis, Dr Clarke and his collaborators reported.

Among patients with only nonregional lymph node metastasis or 3 or fewer bone metastases without visceral metastases, prostate RT recipients had a significant 38% and 43% decreased risk for mortality and treatment failure, respectively, compared with men who received SOC alone, according to the investigators. By comparison, among men with 4 or more bone metastases or any visceral or other metastasis, prostate RT had no significant effect on mortality and was significantly associated with a 13% decreased risk for treatment failure.

“Bone metastatic burden based on conventional imaging is predictive of OS and FFS benefit when prostate RT is added to SOC in newly diagnosed mPCa,” Dr Clarke and his colleagues concluded. “This beneficial effect is most pronounced in patients with up to 3 bone metastases, below which addition of prostate RT to SOC improves survival in patients without visceral or other metastasis. The criteria for low metastatic burden based on conventional imaging, predictive of survival benefit from prostate RT in men with newly diagnosed mPCa, should now include men with M1a disease.”

In an accompanying editorial, Bridget F. Koontz, MD, of Duke University School of Medicine in Durham, North Carolina, and Thomas A. Hope, MD, of the University of California, San Francisco, observed, “While the utility of prostate RT can be debated for a man with castration-sensitive prostate cancer and 4 bone metastases, the overall take-home message is that local RT matters most in men with few metastases and good systemic control and that local RT should be applied more cautiously as the burden of disease increases.” 

Disclosure: This clinical trial was supported by Cancer Research UK, Medical Research Council, Astellas, Clovis Oncology, Janssen, Novartis, Pfizer, and Sanofi Aventis. Please see the original reference for a full list of authors’ disclosures.


Ali A, Hoyle A, Haran AM, et al. Association of bone metastatic burden with survival benefit from prostate radiotherapy in patients with newly diagnosed metastatic prostate cancer: A secondary analysis of a randomized clinical trial. Published online February 18, 2021. JAMA Oncol. doi:10.1001/jamaoncol.2020.7857

Koontz BF, Hope TA. More answers and more questions about radiotherapy for metastatic prostate cancer. Published online February 18, 2021. JAMA Oncol. doi:10.1001/jamaoncol.2020.7708