How RT dose escalation affects prostate Ca outcomes

A meta-analysis of 6,884 men with prostate cancer who underwent external beam radiation therapy reveals surprising findings about dose escalation.

In prostate cancer patients undergoing external beam radiation therapy, escalation of the biologically equivalent dose results in improved freedom from biochemical failure up to 10 years, but does not improve what’s really important to many patients, including overall survival, according to a recent study.

Researchers from several institutions conducted a meta-analysis of 6,884 men with non-metastatic prostate cancer from 12 randomized controlled clinical trials of external beam radiation therapy. The findings were published online in the American Journal of Clinical Oncology (March 24, 2016).

The authors found that increasing biologically equivalent dose correlated with a 10-year improvement in biochemical survival of 9.6% for low-risk and 7.2% for intermediate-risk patients. They also observed that PSA levels decreased as patients received higher doses of radiation, according to a press release from Thomas Jefferson University, Philadelphia, one of the participating institutions. However, the lower PSA scores did not correlate with improvements in overall survival, distant metastasis, or cancer-specific mortality at 5 or 10 years.

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Biologically equivalent dose escalation did not seem to increase acute toxicities, but was associated with increased late gastrointestinal toxicities in patients treated with 3-D conformal radiation therapy. Despite being treated at higher radiation therapy doses, intensity-modulated radiation therapy patients had notably fewer late toxicities.

Next: Takeaways from the study

Senior author Robert Den, MD, told Urology Times that one of the study’s takeaways is that radiation therapy for prostate cancer can be delivered safely, even at increasing doses. The review also suggests that for men with more aggressive or higher risk disease, the combination of radiation with hormone therapy might be more appropriate and that radiation alone with dose escalation is not necessarily sufficient to improve patient survival.

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“There was a lot of discussion in the field about whether patients need hormone therapy, even in the setting of dose escalation. I think that the answer is that the dose escalation, alone, while it provides PSA control, which is an important endpoint for men in terms of their anxiety, may not be sufficient in that our data suggests… it does not improve overall survival,” said Dr. Den, of Sidney Kimmel Medical College at Thomas Jefferson University.

The finding that PSA control did not translate to improved survival was surprising, according to Dr. Den. But the association with PSA and prostate cancer outcomes should be confirmed in larger studies because it could be that the review’s 6,800-plus patients was not a high enough number of subjects, he said.

“The other thing to remember is when you examine the impact of surgery or radiation, you’re looking at initial treatment. It may be that patients who didn’t receive as high a dose of radiation may have undergone subsequent other therapies more often, and those therapies were able to prolong survival such that men would succumb to something else-not the prostate cancer,” he said.

Next: "In which men is a lower dose sufficient?"

What this study doesn’t show, according to Dr. Den, is which men might benefit from radiation therapy dose escalation and which might not.

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“I think the question that we should be directing more research into in order to personalize therapy is understanding in which men do we need to use dose escalation and in which men is a lower dose sufficient?” he said.

The study underscores the importance of having multiple specialties discuss therapy options with prostate cancer patients, according to Dr. Den.

“I think all patients with prostate cancer should be seen by multiple specialties to discuss their treatment options, including urology, radiation oncology, and medical oncology, as appropriate. I think [urologists] should be saying to patients that perhaps not every patient needs to have treatment for as long a duration, and it may be worth discussing with the radiation oncologist whether treatment could be done in a shorter time frame or differently,” he said.