Table 1.
Clinical studies of hypoxia assays and prognosis in localized prostate cancer
| Study | N | T-category | Assay | Prognostic value and details |
|---|---|---|---|---|
| Turaka et al23 | 57 | cT1–3 | pO2 probe | Prognostic: lower prostate/muscle pO2 ratio predicted early biochemical failure after brachytherapy |
| Milosevic et al21 | 247 | cT1–2 | pO2 probe | Prognostic: largest study showing that hypoxia predicted early biochemical relapse after radiotherapy and local recurrence |
| Vergis et al24 | 201 (RT); 289 (surgery) | cT1–3 | IHC-VEGF, HIF-1α, OPN | Prognostic: increased expression of VEGF, HIF-1α and, for patients treated with surgery, OPN identified patients at high risk of biochemical failure |
| Carnell et al18 | 43 | cT1–3 | IHC-PIMO | Not tested, but a positive correlation of PIMO +3 binding with Gleason score was demonstrated |
| Boddy et al17 | 149 | cT1–3 | IHC-VEGF, HIF-1α | Not prognostic: there was a significant correlation between HIF-1α and HIF-2α expression, and with AR and VEGF expression. VEGF was also significantly related to the androgen receptor, whereas PHD2 was inversely related to HIF-2α expression. No significant association was shown between HIF-1α or HIF-2α and time to PSA recurrence |
| Green et al20 | 50 | cT3 | IHC | Prognostic: high VEGF expression was associated with lower disease-specific survival |
| Thoms et al22 | 199 (T1–3); 37 (M1) | cT1–T3 | ELISA-OPN | Not prognostic: within localized prostate cancers plasma OPN was not predictive of more aggressive disease or response to radiotherapy or hormone therapy |
| Weber et al25 | 103 | cT1–3 | IHC | Prognostic: high nuclear expression of HIF-1α and low EGFR expression was associated with a good prognosis in patients treated with RT ± ADT |
| Garcia-Parra et al19 | 14 | pT2b–T3a | PET-FAZA + IHC | Not prognostic: negative 18F-FAZA accumulation and CAIX staining in primary prostate cancer despite documented large lesions (up to 4 cm). HIF-1 staining was positive and independent of Gleason score |
ADT, androgen-deprivation therapy; AR, androgen receptor; CAIX, carbonic anhydrase IX; cT, clinical T-category; EGFR, epidermal growth factor receptor; ELISA, enzyme-linked immunosorbent assay; 18F-FAZA, 18F-labelled fluoroazomycin arabinoside; HIF-1, hypoxia-induced factor 1; IHC, immunohistochemistry; OPN, osteopontin; PET, positron emission tomography; PHD, prolyl hydroxylase enzyme; PIMO, pimonidazole; pO2, partial oxygen concentration; PSA, prostate-specific antigen; pT, pathologic T-category; RT, radiotherapy; VEGF, vascular endothelial growth factor.
pO2, measured with pO2 electrode.