Hypoxia in prostate tumors aids prognosis
MedWire News: Study findings show that hypoxia is associated with early biochemical relapse for prostate cancer after radiotherapy and is predictive for local recurrence in the prostate gland.
"This study provides new evidence that hypoxia in clinically localized prostate cancer influences the outcome of patients after high-dose external beam radiotherapy, with or without neoadjuvant and concurrent hormonal therapy," say Michael Milosevic (Ontario Cancer Institute, Toronto, Canada) and co-researchers.
They add: "[The findings] highlight an important need for better, more widely available ways of directly measuring hypoxia at diagnosis and repeatedly over time in patients with prostate cancer, perhaps using minimally invasive functional magnetic resonance imagining or positron emission tomography imaging techniques."
The pattern of recurrence observed in the study is compatible with the presence of hypoxia-driven occult metastatic disease, as reported in other studies and tumor sites, explain the researchers.
For the study, they measured tumor hypoxia in 247 patients with clinically localized prostate cancer before radiotherapy (with or without hormonal therapy).
Over a median follow-up period of 6.6 years, the researchers found that the median pO2 was 6.8 mmHg and median hypoxic percentage less than 10 mmHg (HP10) was 63%.
Biochemical recurrence was observed in 79 patients, with a biochemical relapse-free rate (bRFR) of 91% at 3 years and 78% at 5 years. Multivariate analysis identified Gleason score (8 vs 6 or 7; hazard ratio=2.66) and prostate specific antigen (PSA) as the only significant, independent clinical predictors of recurrence.
Further analysis showed that the effect of HP10 on bRFR was greatest early in follow up and diminished with increasing time, suggesting that patients with hypoxic tumors were significantly more likely than those with well-oxygenated tumors to develop biochemical failure within the first 48 months of completing treatment, but not at later times.
Hypoxia remained a significant predictor of early biochemical relapse after correcting for Gleason score and PSA. Furthermore, the relationship between hypoxia and early bRFR was more pronounced when the analysis was restricted to 142 patients with bulk tumors at the site of oxygen measurements.
Transrectal ultrasound or magnetic resonance image-guided prostate biopsies conducted among 70 patients an average of 34 months after completion of treatment showed that tumors were identified in 69% of biopsies, including 86% of those with biochemical failure. As seen with bRFR, the effect of hypoxia on local relapse-free rate was greatest in early follow up and diminished with increasing time.
Writing in Clinical Cancer Research, the team says the findings raise "several intriguing questions about the underlying mechanisms of treatment failure and disease progression that will be addressed with longer follow-up, and in future companion studies using biopsies obtained at the same time and from the same sites as the oxygen measurements."
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By Ingrid Grasmo