KEY POINTS
- The editorial builds on established international pain-response criteria and the recent Delphi consensus for stereotactic body radiotherapy studies in bone metastases. It argues that endpoint selection should reflect whether treatment aims to relieve symptoms, control tumour, preserve function or prevent complications.
- Established pain-response criteria combine pain intensity with opioid use and classify complete response, partial response, progression and indeterminate response. The exploratory Clinical Bone Response Assessment Criteria add stable disease and refine the indeterminate category, but require validation before replacing existing standards.
- Pain and analgesic changes should be attributed to the protocol-defined index site. Missing data, opioid escalation for unrelated pain, pain flare and true index-site progression should not be combined within a single indeterminate category.
- Pain response and local tumour control are distinct. Radiological progression may occur without worsening pain, while persistent pain may reflect fracture, instability, inflammation or unrelated disease despite local tumour control.
- Trial assessment should combine patient-reported index-site pain with function, neurological and ambulatory status, imaging, toxicity, skeletal-related events and health-related quality of life. Composite endpoints may be used, but every component should also be reported separately.
- Prevention trials for asymptomatic high-risk lesions require endpoints such as pain progression, pathological fracture, malignant spinal-cord compression, surgery, unplanned radiotherapy, hospitalization, mobility and quality of life rather than conventional pain-response rates.
- Imaging modality, timing and adjudication should be prespecified because sclerosis, fracture, persistent marrow abnormality and inflammation after stereotactic radiotherapy can mimic progression. Trials should also distinguish new from worsening fractures and use competing-risk methods when death prevents observation of local or skeletal events.
CLINICAL TAKEAWAY
Pain response should remain the primary patient-centred endpoint when symptom relief is the purpose of treatment, but it cannot define success in local-control or prevention trials. The proposed framework improves trial interpretation rather than prescribing treatment, and newer categories such as Clinical Bone Response Assessment Criteria should be reported alongside established endpoints until prospectively validated.