More Radiation May Not Improve Survival in Localized Prostate Cancer

Escalating the dose of radiation may not lead to increased survival for patients with localized and locally advanced prostate cancer (PCa), a new study finds.

“In the field of radiation oncology, we often assume that the highest dose that the body can tolerate will be most effective at killing cancer,” lead researcher Robert Den, MD, associate professor of radiation oncology, cancer biology, and urology at Thomas Jefferson University in Philadelphia, stated in a press release. “Our results argue that this may not be the case, at least not with lower-risk prostate cancer patients.”

Dr Den and colleagues analyzed data from 12 randomized controlled trials of external beam radiation therapy (EBRT) published after 1990. The studies included a total of 6,884 men (aged 67-75) with non-metastatic prostate cancer (PCa). Of these, 5,506 men were treated in trials of conventionally fractionated EBRT (CFRT) dose escalation and 1,828 men in trials of CFRT versus hypofractionated EBRT (HFRT). EBRT reached a dose of 180-200 Gy, assuming an α/β of 1.5.

The researchers looked at biochemical failure, as reflected by a rising PSA (using the Phoenix or ASTRO definitions) as well as overall survival, distant metastasis, and cancer-specific mortality.  

Mixed effects regression models using weighting revealed that increasing the biologically equivalent dose of EBRT correlated with greater freedom from biochemical failure. Absolute rates at 10 years were 9.6% and 7.2% for patients with low-risk and intermediate-risk PCa, respectively, according to results published online ahead of print in the American Journal of Clinical Oncology. But there were no meaningful improvements in survival, metastasis, or cancer-specific mortality.

Reliance on the PSA test as a marker for patient outcomes may not as useful as many believe, at least for EBRT, Dr Den and colleagues concluded. They suggested future studies include other biomarkers and use imaging to help distinguish cancerous from benign tissue.

With regard to toxicities, radiation dose escalation correlated with a 1.5% increase in late gastrointestinal toxicities in patients treated with 3-dimensional conformal radiotherapy. Men treated with intensity-modulated radiotherapy had significantly fewer late toxicities. 

​In a discussion of study limitations, the investigators acknowledged that they could not perform a pooled analysis. They also lacked information on patient cancer characteristics, comorbidities, salvage therapies, androgen deprivation usage, and race, which may influence results.

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