Post-operative radiotherapy in surgically treated bone metastases (PORTRAIT) – a multi-centre, randomised controlled trial

Research summary

Research question: Does post-operative radiotherapy following surgery for pathological fractures improve pain and quality of life? Background: Approximately 70% of people with advanced breast and prostate cancer develop bone metastases, causing ‘pathological’ fractures requiring surgery to stabilise or replace the affected bone. Following surgery, patients usually receive radiotherapy (RT). Despite widespread use, no high-quality evidence exists that post-operative RT improves pain, quality of life nor reduces the risk of re-operation. RT has side-effects, requires additional hospital visits and scans, can delay other effective treatments which may cause patients anxiety and use scarce NHS resource. It is therefore essential to understand if any benefits justify additional harms and cost. Methods: A multi-centre, two arm, parallel group, non-inferiority randomised controlled trial with an internal pilot, and embedded economic evaluation. Intervention and Comparator: Intervention: No immediate post-operative radiotherapy (within 10 weeks of surgery): Routine clinical monitoring will be undertaken and if patients develop progressive local symptoms radiotherapy may be offered after this period. Comparator: Immediate post-operative radiotherapy (within 10 weeks of surgery): Delivered using the preferred regimen of the treating Clinical Oncologist 4-10 weeks following surgery. Objectives: Primary objective: To undertake a multi-centre, two-arm, parallel group, RCT to determine whether no immediate radiotherapy (within the first 10 weeks after surgery) is non-inferior to immediate radiotherapy (within the first 10 weeks) following surgery for bone metastases in terms of pain interference measured by the Brief Pain Inventory (BPI) at four months post-randomisation. Secondary objectives: - To undertake a 12-month internal pilot to determine the feasibility of the study, in particular recruitment rate and completeness of follow-up - To undertake an analysis of secondary outcomes to assess the impact of radiotherapy on pain interference and severity, quality of life, functional status, survival and rate of re-operation at 4-, 8-, 12-, and up to 18-months post randomisation. - To determine the cost-effectiveness of the two treatment options from the NHS perspective to inform the most efficient provision of future NHS care. - To undertake a Study within a Trial (SWAT) to evaluate the effectiveness of different types of incentives (cash vs voucher) on participant retention at the primary end point. Setting: A minimum of 20 UK study sites from an established network of metastatic bone surgical centres [1]. These sites are geographically broadly distributed and include sites within the top decile for deprivation. Site selection will ensure a diverse range of demographic and socio-economic groups participate. Target population: Adults undergoing surgery for impending or completed pathological fractures due to (non-spinal) bone metastases. The target sample size is 350 patients. Randomisation: Participants will be randomised 1:1 to the intervention or control group using block randomisation with varying block sizes stratified by type of fracture (impending vs completed) and cancer diagnosis (myeloma vs solid-organ cancers). An independent statistician will generate the allocation schedule, and this will be implemented via a secure, web-based randomisation system. How long is the study expected to run for? June 2025 to May 2029. Anticipated impact and dissemination: Evidence from this trial will allow NICE to update their guidance regarding the role and indications for post-operative radiotherapy for bone metastases. Dissemination will be through the media, conferences, peer reviewed journals, and clinical guidelines. References: 1 Archer JE, Chauhan GS, Osman K, et al. The British Orthopaedic Oncology Management audit protocol. J Surg Protoc Res Methodol 2021;2021. doi:10.1093/JSPRM/SNAB005. 2 Brief Pain Inventory (BPI) English Sample | MD Anderson Cancer Center. 1991. https://www.mdanderson.org/documents/Departments-and-Divisions/Symptom-Research/BPI-SF_English-24h_Original_SAMPLE.pdf (accessed 04 August 2025). 3 Cleeland CS. The Brief Pain Inventory User Guide. https://www.mdanderson.org/documents/Departments-and-Divisions/Symptom-Research/BPI_UserGuide.pdf (accessed 04 August 2025). 4 Brief Pain Inventory (BPI) | MD Anderson Cancer Center. https://www.mdanderson.org/research/departments-labs-institutes/departments-divisions/symptom-research/symptom-assessment-tools/brief-pain-inventory.html (accessed 04 August 2025). 5 Chow E, Zeng L, Salvo N, et al. Update on the systematic review of palliative radiotherapy trials for bone metastases. Clin Oncol (R Coll Radiol) 2012; 24:112–24. doi:10.1016/J.CLON.2011.11.004. 6 New UK EQ-5D-5L Valuation Study | BLOG – EQ-5D. https://euroqol.org/about-us/blogs/ (accessed 04 August 2025). 7 Ploetze KL, Dalton JF, Calfee RP, et al. Patient-Reported Outcomes Measurement Information System physical function correlates with Toronto Extremity Salvage Score in an orthopaedic oncology population. J Orthop Transl 2019;19:143–50. doi:10.1016/J.JOT.2019.02.004. 8 Raschka T, Weiss S, Reiter A, et al. Outcomes and prognostic factors after surgery for bone metastases in the extremities and pelvis: A retrospective analysis of 140 patients. J Bone Oncol 2022;34:100427. doi:10.1016/J.JBO.2022.100427.

Principal Investigator

Ather Siddiqi

Contact us

Email: gail.lang@ndorms.ox.ac.uk

IRAS number

333375