Hypoxia often occurs early in solid tumor development as a result of imbalances between oxygen supply and consumption and may lead to genetic and molecular signaling that influences the biology and clinical behavior of tumors and response to treatment. Milosevic and colleagues from Princess Margaret Hospital and Ontario Cancer Institute in Toronto recently showed that hypoxia is an independent predictor of biochemical recurrence of prostate cancer after radiotherapy alone or together with neoadjuvant and concurrent hormonal therapy.
Early Failure Preferentially Predicted
In this study, direct oxygen measurements were made prior to treatment in 247 patients with clinically localized prostate cancer who were followed for over 6 years. When added to a baseline clinical model consisting of Gleason score and prostate-specific antigen level, hypoxia was an independent predictor of early biochemical relapse-free survival. Its effect as a predictor was even more pronounced when analysis was limited to 142 patients with bulk tumor at the oxygen measurement site. As noted by the investigators, this finding contributes to other emerging evidence “indicating that early biologic and clinical behavior [of the tumor] is determined by the dominant focus of disease in the prostate gland and less so by secondary more indolent foci.”
On univariate analysis, the effect of hypoxia on biochemical relapse-free survival was greatest earlier in follow-up and diminished with increasing time. Patients with hypoxic tumors were more likely than those with well-oxygenated tumors to develop biochemical failure within the first 48 months of completing treatment but not at longer durations after the end of treatment. Hypoxia was the only factor predictive of local recurrence in 70 patients who had biopsies conducted during follow-up, with the effect again being greatest early after completing treatment.
These findings support the hypothesis that hypoxia influences clinical outcome after radiotherapy in intermediate-risk prostate cancer and provide a rationale for studying the combination of radiotherapy with new hypoxia-targeted treatment approaches. As stated by the investigators, “New treatment approaches for high-risk patients with hypoxic tumors might consist of further radiation dose-escalation, the use of hypoxic cell sensitizers or cytotoxins in combination with radiotherapy, or molecular therapeutic strategies that either alter the balance between oxygen supply and consumption or exploit the molecular consequences of hypoxia to enhance radiation response, tumor control, and patient survival.” ■
Milosevic M, et al: Clin Cancer Res 18:2108-2114, 2012.