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Tumor Hypoxia Has Independent Predictor Impact Only in Patients With Node-Negative Cervix Cancer

From the Departments of Radiation Oncology, Medicine, Biostatistics, Clinical Informatics, and Experimental Therapeutics, Ontario Cancer Institute/Princess Margaret Hospital, University Health Network and University of Toronto, Toronto, Canada.

Address reprint requests to Anthony Fyles, MD, Department of Radiation Oncology, Rm 5-984, Princess Margaret Hospital, 610 University Ave, Toronto, Ontario, Canada M5G 2M9; email: anthony.fyles{at}rmp.uhn.on.ca

PURPOSE: This prospective clinical study was begun in 1994 to validate the independent prognostic impact of tumor hypoxia in patients with cervix cancer treated with definitive radiation therapy.

PATIENTS AND METHODS: Between May 1994 and January 1999, 106 eligible patients with epithelial cervix cancer had tumor oxygen pressure (PO₂) measured using the Eppendorf probe. Oxygenation data are presented as the hypoxic proportion, defined as the percentage of PO₂ readings less than 5 mm/Hg (abbreviated as HP₅) and the median PO₂.

RESULTS: The median HP₅ in individual patients was 48%, and the median PO₂ was HP₅. Progression-free survival (PFS) for patients with hypoxic tumors (HP₅ > 50%) was 37% at 3 years versus 67% in those patients with better oxygenated tumors (P = .004). In multivariate analysis, only tumor size (risk ratio [RR], 1.33; P = .0003) and evidence of pelvic nodal metastases on imaging studies (RR, 2.52; P = .0065) were predictive of PFS. However, an interaction between nodal status and oxygenation was observed (P = .006), and further analysis indicated that HP₅ was an independent predictor of outcome in patients with negative nodes on imaging (P = .007). There was a significant increase in the 3-year cumulative incidence of distant metastases in the hypoxic group (41% v 15% in those with HP₅ < 50%; P = .0023), but not in pelvic relapse (37% v 27%; P = .12).

CONCLUSION: Tumor hypoxia is an independent predictor of poor PFS only in patients with node-negative cervix cancer, in addition to tumor size. Its impact appears to be related to an increased risk of distant metastases rather than to an effect on pelvic control.

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