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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.


ABSTRACT:

Importance

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.

Trial registration

ClinicalTrials.gov Identifier: NCT00268476; ISRCTN.com Identifier: ISRCTN78818544.

SUBMITTER: Ali A 

PROVIDER: S-EPMC7893550 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

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.

Ali Adnan A   Hoyle Alex A   Haran Áine M ÁM   Brawley Christopher D CD   Cook Adrian A   Amos Claire C   Calvert Joanna J   Douis Hassan H   Mason Malcolm D MD   Dearnaley David D   Attard Gerhardt G   Gillessen Silke S   Parmar Mahesh K B MKB   Parker Christopher C CC   Sydes Matthew R MR   James Nicholas D ND   Clarke Noel W NW  

JAMA oncology 20210401 4


<h4>Importance</h4>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.<h4>Objective</h4>To evaluate the association of bone metastasis count and location with survival benefit from prostate RT.<h4>Design, setting, and participants</h4>This exploratory analysis of treatment outcomes based on me  ...[more]

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