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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

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    Authors
    Ali, Adnan
    Hoyle, Alex P
    Haran, Aine M
    Brawley, C. D.
    Cook, A.
    Amos, C.
    Calvert, J.
    Douis, H.
    Mason, M. D.
    Dearnaley, D
    Attard, G.
    Gillessen, Silke
    Parmar, M. K. B.
    Parker, C. C.
    Sydes, M. R.
    James, N. D.
    Clarke, Noel W
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    Affiliation
    Genito-Urinary Cancer Research Group, Division of Cancer Sciences, The University of Manchester, Mancheste
    Issue Date
    2021
    
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    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.
    Citation
    Ali A, Hoyle A, Haran AM, Brawley CD, Cook A, Amos C, 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. JAMA Oncol. 2021.
    Journal
    JAMA Oncology
    URI
    http://hdl.handle.net/10541/623816
    DOI
    10.1001/jamaoncol.2020.7857
    PubMed ID
    33599706
    Additional Links
    https://dx.doi.org/10.1001/jamaoncol.2020.7857
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1001/jamaoncol.2020.7857
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