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

KEY POINTS

Question
 Are bone metastatic burden and site associated with survival benefit from the addition of prostate radiotherapy (RT) to standard-of-care systemic therapy in newly diagnosed metastatic prostate cancer?

Findings This exploratory analysis of 1939 participants in a randomized clinical trial shows that survival benefit following prostate RT gradually diminished with increasing bone metastasis number, with survival benefit most pronounced in patients with up to 3 bone metastases. Prostate RT was associated with greater overall and failure-free survival in patients with only nonregional lymph node metastasis (M1a) or 3 or fewer bone metastases without visceral metastasis.

Meaning In patients with prostate cancer, bone metastatic burden and metastasis location may be useful in predicting survival benefit from prostate RT.  

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 have 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

Adnan Ali, MBBS1,2,3 Alex Hoyle, MBBS, MRCS, MD1,2,3,4 Áine M. Haran, MRCS1,2,3,4 Christopher D. Brawley, MSc5 Adrian Cook, MSc5 Claire Amos, PhD5 Joanna Calvert, MSc5 Hassan Douis, PhD6 Malcolm D. Mason, MD7 David Dearnaley, MA, MD8 Gerhardt Attard, MD, PhD9 Silke Gillessen, MD10,11,12 Mahesh K. B. Parmar, DPhil5 Christopher C. Parker, MD8 Matthew R. Sydes, MSc5 Nicholas D. James, MBBS, PhD8 Noel W. Clarke, MBBS, ChM1,2,3,4

  1. Genito-Urinary Cancer Research Group, Division of Cancer Sciences, The University of Manchester, Manchester, United Kingdom
  2. FASTMAN Centre of Excellence, Manchester Cancer Research Centre, Manchester, United Kingdom
  3. Department of Surgery, The Christie NHS Foundation Trust, Manchester, United Kingdom
  4. Department of Urology, The Salford NHS Foundation Trust, Manchester, United Kingdom
  5. MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London, United Kingdom
  6. Department of Radiology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
  7. Cardiff University, Cardiff, United Kingdom
  8. Royal Marsden Hospital and The Institute of Cancer Research, London, United Kingdom
  9. UCL Cancer Institute, London, United Kingdom
  10. Division of Cancer Sciences, The University of Manchester, Manchester, United Kingdom
  11. Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
  12. Università della Svizzera Italiana, Lugano, Switzerland
Source: Ali A, Hoyle A, Haran ÁM, 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. Published online February 18, 2021. doi:10.1001/jamaoncol.2020.7857


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