Why Prostate Cancer Sometimes Returns

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ORLANDO—New findings may explain why some men treated with radiotherapy for localized prostate cancer experience biochemical relapse.

“After several years of research, we were able to show that low levels of oxygen within the prostate are highly related to a patient's outcome,” said senior investigator Benjamin Movsas, MD, Chairman of the Department of Radiation Oncology at Henry Ford Hospital in Detroit.

Researchers were the first to measure the partial pressure of oxygen (Po2) in human prostate cancer and they were able to show that patients whose prostate cancer demonstrated lower oxygen levels had a higher chance of the cancer recurring after radiation therapy, he added.

“By identifying patients with low oxygen levels in prostate tumors, we would like to build on this research and begin to explore novel treatment options for this small subset of patients. It's possible we'll find that these patients will do best with a combination of radiation therapy and other novel approaches, such as angiogenesis therapy.”

Tumor hypoxia is a well-known risk factor for radiation resistance in solid tumors. Between 2000 and 2002, researchers at Fox Chase Cancer Center in Philadelphia published several research papers detailing the link between tumor hypoxia, radioresistance, and the risk of increased PSA levels.

However, the mean follow-up at the time of those studies was only 19 months. The current study, which was presented at the American Society of Clinical Oncology Annual Meeting, reinforces those preliminary findings, now with a mature median follow-up of eight years.

Researchers used a custom-built probe to monitor the Po2 in prostate cancer tumors (P) relative to the Po2 in noncancerous muscle tissue (M), resulting in a P/M Po2 ratio. The probe was used on 57 patients with low-or intermediate-risk disease just before they received brachytherapy for prostate cancer. The researchers then tracked the patients over time, looking for a correlation between P/M Po2 at the time of therapy and cancer recurrence.

Eight of the 57 patients experienced a post-treatment increase in PSA levels, defined as an increase of 2 ng/mL above the lowest PSA reading. Overall, average Po2 in the muscle of the patients who subsequently had biochemical relapse was 12.5 times higher than of the Po2 in the tumor (30 vs. 2.4 mm Hg).

Using a statistical model that accounted for such risk factors as tumor grade, initial PSA level, and stage, the researchers determined that hypoxia was a significant independent predictor of subsequent biochemical failure. Even after accounting for initial PSA value, Gleason score, tumor stage, age, and other prostate cancer risk factors, tumor hypoxia alone could predict the likelihood of tumor recurrence.

The new findings are clinically significant because they confirm previous studies and involve long-term follow-up, said co-investigator Aruna Turaka, MD, a radiation oncology fellow at Fox Chase Cancer Center. Using tumor hypoxia as an independent predictor of prostate cancer recurrence could significantly change the way some patients are managed in terms of radiation or other therapies, as recent studies suggest low oxygen in prostate cancer also predicts for failure after surgery.

“We already knew that there are hypoxic regions within cancers,” Dr. Turaka said. “The future goal is to interpolate [how that hypoxia relates] to the expression of molecular markers, such as hypoxia-inducible factor-1α, and attack those tumors with hypoxic-specific strategies.”

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