Hormone therapy works best when combined with radiation for locally advanced prostate cancer

By Charlie Schmidt

When prostate cancer spreads from the prostate gland into nearby lymph nodes or bladder tissue, it is called locally advanced prostate cancer. The standard treatment for it is a combination of radiation therapy and hormone therapy. Radiation kills prostate cancer cells. Hormone therapy, formally known as androgen deprivation therapy (ADT), deprives prostate cancer cells of testosterone, which they need in order to grow and spread.

But both types of therapy have their own sets of side effects. So is such a one-two punch really needed? It is. That’s the conclusion drawn from the largest clinical trial of the combination to date.

Using radiation therapy plus ADT against locally advanced prostate cancer came into favor after studies began showing that men treated with both radiation and ADT lived longer than men treated with radiation alone. In one such study, French researchers divided 415 men with locally advanced prostate cancer into two groups: one group was treated with radiation only, while the other group was treated with radiation and three years of ADT. Ten years later, 60% of the men on the combination treatment were still alive, compared with 40% of those who had been treated with radiation only.

What that and other studies did not investigate was how combination therapy stacks up against ADT alone. An international research team has addressed this question, and the results strongly favor combination therapy.

“Adding radiation to ADT more than halved the risk of dying from locally advanced prostate cancer,” said Malcolm Mason, a professor at Cardiff University in Wales and lead author of the study.

Mason and his colleagues enrolled 1,205 men between the ages of 50 and 80 who were diagnosed with locally advanced prostate cancer between 1995 and 2005. Half of the men were treated with lifelong ADT; the other half were treated with ADT plus a seven-week course of radiation.

After 10 years, 43% of the men treated with ADT alone had died, compared to 34% of the men treated with ADT plus radiation. That translates into a 30% lower risk of death from any cause in the combined treatment group. Deaths specifically from prostate cancer were nearly 50% lower among men who got ADT plus radiation. Mason cites that as the study’s take-away conclusion. The results were published in the Journal of Clinical Oncology.

Side effects were roughly comparable in the two treatment groups, with about one in three men reporting a low sex drive and difficulty getting or keeping an erection. Other side effects included bowel problems, hot flashes, and a frequent urge to urinate, which were all slightly more common in the combined treatment arm.

“This paper is significant because it shows that ADT by itself is not enough for men with locally advanced prostate cancer,” said Dr. Marc Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and Editor in Chief of HarvardProstateKnowledge.org. “They also need radiation therapy.”

But Garnick points out that a critical question remains: as part of combination therapy, how long should ADT last? In a separate study, the French researchers showed that three years of ADT was more effective than six months. But ADT can be difficult to tolerate, and some men in the trial’s three-year treatment arm weren’t able to complete it.

“We try to give at least two years of ADT to men with high-risk disease, but it depends on what they can tolerate,” Garnick said. “And as the optimal duration isn’t known, this will require further study.”