Angiogenic and hypoxia biomarkers may predict outcome and benefit of dose escalation in patients receiving external beam radiotherapy (EBRT) alone or combined with high-dose-rate brachytherapy boost (HDR-BTb) for localised prostate cancer. That is the finding of research led by the Institute of Cancer Research Clinical Trials and Statistics Unit (ICR-CTSU) in London.
The study, published in the journal Radiotherapy & Oncology, prospectively collected prostate biopsy samples from patients entered into a phase 3 randomised controlled trial of EBRT or EBRT + HDR-BTb. Analyses were performed to identify associations between immunohistochemical staining of hypoxia inducible factor 1 alpha (HIF1α), glucose transporter 1 (GLUT1), osteopontin (OPN), and microvessel density (MVD) with clinical outcome.
Immunohistochemistry was available for 204 patients.
The data showed that increased expression of OPN (hazard ratio [HR] 2.38; 95% CI 1.06-5.34; P<0.036) and GLUT1 (HR 2.36; 95% CI 1.39-4.01; P<0.001) were predictive of worse biochemical relapse free survival (BRFS).
Increased GLUT1 expression was also predictive of worse distant metastasis free survival (HR 2.22; 95% CI 1.02-4.84; P=0.045).
Increased MVD (HR 1.82, 95% CI 1.06-3.14; P=0.03) and OPN (HR 1.82; 95% CI 1.06-3.14; P=0.03) and reduced GLUT1 expression (HR 0.40; 95% CI 0.20-0.79; P=0.009) were predictive of improved BRFS in patients receiving EBRT + HDR-BTb.
The authors say the data suggest these angiogenic and hypoxia biomarkers may predict outcome and benefit of dose escalation in this patient population. However, they add that further validation is required in prospective studies, which should also examine hypoxia modification.
