Dr. Michael Zelefsky of Memorial Sloan Kettering Cancer Center talks with Prostatepedia about using androgen deprivation therapy alongside radiation therapy for prostate cancer (Download Prostatepedia’s August issue to read the interview.)
Is androgen deprivation therapy (ADT) used in combination with radiation therapy? Before, during, or after radiation therapy? Are there specific forms of ADT used?
Dr. Zelefsky: Many trials have been conducted over the last 20 and 30 years, which have demonstrated very clearly for more advanced high-risk tumors—especially patients with a Gleason 8 or higher or with a disease that has breached the capsule of the prostate—that utilizing hormones together with radiation has been associated with improved outcomes. A number of those studies demonstrated improved survival outcomes, as well. Using ADT with radiation therapy has become standard of care for patients with high-grade disease or aggressive-risk disease. In this country, ADT is very often given before the radiation starts for two or three months, continued during the radiation, and for a prolonged period of time after radiation.
Some studies, in particular one from Canada, suggested 18 months would be satisfactory for high-risk disease. A number of other studies used two or three years of hormonal therapy in conjunction with radiation treatment. It appears that these longer courses of hormonal therapy are associated with better results than shorter courses of six months or less for these high-risk patients.
It is unclear which is the optimal type of hormonal therapy. LHRH agonists such as Lupron (leuprolide) or Zoladex (goserelin), and more recently the LHRH antagonist Firmagon (degarelix), are used. Some studies have indicated that Firmagon (degarelix) may be associated with fewer cardiac-related side effects in the long run compared with other available hormonal therapy agents.
Fewer cardiac side effects in men who’ve had radiation therapy and taken the drug or just fewer cardiac side effects in any man who has taken the drug?
Dr. Zelefsky: In anybody taking the agent in general. There are other studies that have shown improved survival outcomes in patients with intermediate-risk disease.
Using hormonal therapy together with more standard radiation doses is associated with improved outcomes and, as I said, improved survival outcomes. When using external radiation therapy, a short course of hormonal therapy is now considered standard of care because of the two trials that demonstrate a benefit.
Of course, we counsel patients that there are side effects associated with hormonal therapy. ADT has an impact on a patient’s quality of life. But the potential benefit of improved outcome needs to be taken into consideration when using radiation. In the last several years, it has become standard to utilize hormones together with radiation—longer courses for high-risk disease, shorter courses of about six months for intermediate-risk disease.
Of course, a remaining question, which trials are now addressing, is whether hormonal therapy is needed when you use very intense radiation doses like seed implants combined with radiation. A radiation therapy oncology group study called the RTOG is currently looking at that very issue.
So they’re taking information we learned during the ASCENDE trial and adding ADT?
Dr. Zelefsky: Right. The ASCENDE trial asked whether the combined modality was better. But we have additional questions. Could you avoid hormonal therapy in such cases, or is it still necessary?