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Association of Bone Metastatic Burden With Survival Benefit From Prostate Radiotherapy in Patients With Metastatic Prostate Cancer
TAKE-HOME MESSAGE
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This exploratory analysis used data from the STAMPEDE trial to explore the association between bone metastatic burden and treatment outcomes following radiation therapy. Patients included in the STAMPEDE trial's M1 radiotherapy comparison report were eligible for inclusion in this analysis. The results indicated that the number of bone metastases present is predictive of survival benefit when adding prostate radiation for newly diagnosed metastatic prostate cancer. This benefit was most pronounced in the setting of three or fewer bone metastases. Additionally, patients with visceral or other metastases, aside from nonregional lymph node metastases, had no benefit in survival with the addition of radiation to the prostate.
- The authors conclude that bone metastases count and location are associated with overall survival and failure-free survival benefit from prostate radiotherapy in M1 disease.
abstract
This abstract is available on the publisher's site.
Access this abstract nowImportance
Prostate radiotherapy (RT) improves survival in men with low-burden metastatic prostate cancer. However, owing to the dichotomized nature of metastatic burden criteria, it is not clear how this benefit varies with bone metastasis counts and metastatic site.
Objective
To evaluate the association of bone metastasis count and location with survival benefit from prostate RT.
Design, Setting, and Participants
This exploratory analysis of treatment outcomes based on metastatic site and extent as determined by conventional imaging (computed tomography/magnetic resonance imaging and bone scan) evaluated patients with newly diagnosed metastatic prostate cancer randomized within the STAMPEDE trial's metastasis M1 RT comparison. The association of baseline bone metastasis counts with overall survival (OS) and failure-free survival (FFS) was assessed using a multivariable fractional polynomial interaction procedure. Further analysis was conducted in subgroups.
Interventions
Patients were randomized to receive either standard of care (androgen deprivation therapy with or without docetaxel) or standard of care and prostate RT.
Main Outcomes and Measures
The primary outcomes were OS and FFS.
Results
A total of 1939 of 2061 men were included (median [interquartile range] age, 68 [63-73] years); 1732 (89%) had bone metastases. Bone metastasis counts were associated with OS and FFS benefit from prostate RT. Survival benefit decreased continuously as the number of bone metastases increased, with benefit most pronounced up to 3 bone metastases. A plot of estimated treatment effect indicated that the upper 95% CI crossed the line of equivalence (hazard ratio [HR], 1) above 3 bone metastases without a detectable change point. Further analysis based on subgroups showed that the magnitude of benefit from the addition of prostate RT was greater in patients with low metastatic burden with only nonregional lymph nodes (M1a) or 3 or fewer bone metastases without visceral metastasis (HR for OS, 0.62; 95% CI, 0.46-0.83; HR for FFS, 0.57; 95% CI, 0.47-0.70) than among patients with 4 or more bone metastases or any visceral/other metastasis (HR for OS, 1.08; 95% CI, 0.91-1.28; interaction P = .003; HR for FFS, 0.87; 95% CI, 0.76-0.99; interaction P = .002).
Conclusions and Relevance
In this exploratory analysis of a randomized clinical trial, bone metastasis count and metastasis location based on conventional imaging were associated with OS and FFS benefit from prostate RT in M1 disease.
Additional Info
Disclosure statements are available on the authors' profiles:
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
JAMA Oncol 2021 Feb 18;[EPub Ahead of Print], A Ali, A Hoyle, ÁM Haran, CD Brawley, A Cook, C Amos, J Calvert, H Douis, MD Mason, D Dearnaley, G Attard, S Gillessen, MKB Parmar, CC Parker, MR Sydes, ND James, NW ClarkeFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Advanced Prostate Cancer Center of Excellence
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Advanced Prostate Cancer
This is an update on STAMPEDE arm H, and it evaluates in detail metastatic disease patterns and the number of metastases and the benefit from treating the prostate with radiation in those men with metastatic castrate-sensitive disease. Keep in mind that these patients are predominately just treated with androgen deprivation therapy (ADT), and novel hormones were not included in this patient population.
They found that there was a benefit to radiating the prostate if there were three or fewer bony metastases through radiating the prostate — and remember that these are patients with metastatic castrate-sensitive prostate cancer.
The important finding was for three or fewer bony metastases; there was clear benefit from radiating the prostate in terms of prolonging survival.
The bottom line is that treating the prostate in those with metastatic disease is appropriate therapy for those who have limited bony metastases, and this should be incorporated, potentially, into clinical practice. More studies are appropriate when including ADT and novel hormones such as abiraterone or enzalutamide.