Different doses and combinations of external beam radiation therapy examined

This study compared different external beam radiation therapy (EBRT) approaches for localized prostate cancer. Authors reported high effectiveness with higher doses of radiation therapy, particularly when hormone therapy was added to treatment. However, these combinations were also associated with the highest rate of side effects.

Approximately 90% of men diagnosed with prostate cancer have disease confined to the prostate gland (localized prostate cancer). External beam radiation therapy (EBRT) is the most common treatment for localized prostate cancer. EBRT involves directing high-energy rays from outside the body at the tumor site to kill cancer cells. Androgen deprivation therapy (ADT) can be added to radiation therapy in short (less than 10 months) or long courses (more than 2 years) for a more intensive intervention. Whether low-dose, high-dose, or hypofractioned EBRT (H-EBRT), with or without ADT, is more effective relative to treatment-related side effects is still under investigation. H-EBRT involves giving larger doses of radiation per treatment, reducing the number of total treatments.

The results of 27 separate trials were pooled into a single analysis to examine the effectiveness of different EBRT approaches. The analysis included a combined total of 13,364 men with localized or locally advanced prostate cancer (tumor protruding into nearby tissue). Men received treatment with 1 of 7 EBRT approaches: either low-dose EBRT alone (group 1), high-dose EBRT alone (group 2), low-dose EBRT with a short ADT course (group 3), low-dose EBRT with a long ADT course (group 4), high-dose EBRT with a short ADT course (group 5), H-EBRT alone (group 6), or H-EBRT with a short ADT course (group 7). Treatment outcomes were followed for an average of 5 to 10 years.

The risk of overall mortality (death from any cause) was lower when ADT was added to low-dose EBRT (groups 3 and 4) compared to low-dose EBRT alone (group 1). It was 36% lower when ADT was given in a long course and 25% lower when ADT was given as a short course. 

Cancer-specific mortality was lowest among men receiving H-EBRT with ADT (group 7). It was 76% lower relative to H-EBRT alone (group 6), and 86% lower compared to group 1. Combining either a short or a long course of ADT with either high- or low-dose EBRT also reduced cancer-specific mortality compared to EBRT alone (by 40 to 57%). However, high-dose EBRT reduced cancer-specific mortality significantly more than low-dose EBRT.

Overall, higher doses of EBRT, with and without ADT, were associated with significantly lower cancer recurrence rates than lower doses of EBRT.

No significant differences in side effects between the 7 treatment groups were observed, However, high-dose EBRT was associated with significantly more gastrointestinal side effects compared to low-dose EBRT. Side effects were also somewhat higher in group 7.

Authors concluded that higher doses of EBRT, as well as H-EBRT, combined with ADT were most effective in reducing mortality rates and cancer recurrence rates. However, these combinations were also associated with the highest rate of side effects.