Available evidence does not support the early use of androgen-deprivation therapy in men whose prostate cancer recurs after treatment, according to clinical practice guidelines issued by the American Society of Clinical Oncology.
In addressing the controversial issue, the ASCO guidelines recommend that hormone therapy be deferred in such patients until they experience symptoms of their disease.
The expert panel that drafted the document—an update of ASCO's 2004 guidelines for the initial management of androgen-sensitive prostate cancer that is metastatic, recurrent, or progressive—failed to find an overall survival advantage for early use of hormone therapy, compared with later use (J. Clin. Oncol. 2007 April 2 [Epub DOI:10.1200/ JCO. 2006.10.1949]).
After performing a meta-analysis of seven studies that involved more than 5,000 patients, the panel concluded that early hormone therapy was associated with a 17% decrease in mortality from prostate cancer, but a 15% increase in mortality from other causes.
“Hormones are not benign. We have been thinking that they are bothersome because they cause hot flashes, fatigue, low sex drive, and thin bones. But the more we study this, the more aware we become that there are serious side effects associated with the hormones,” lead author Dr. Andrew Loblaw said in an interview.
One of the most serious of these side effects is hip fracture due to osteoporosis. Many patients are unaware that a hip fracture increases mortality risk by 33% within the first month and 67% within the first year.
Doctors should discuss with their patients the risks and benefits of early hormone therapy, compared with deferred therapy. If a patient prefers to defer therapy, he should have regular visits with his physician every 3–6 months to monitor the disease, said Dr. Loblaw, of the Toronto-Sunnybrook Regional Cancer Centre, Toronto.
The panel suggested either bilateral orchiectomy or injections with luteinizing hormone-releasing hormone (LHRH) analogues as initial androgen-deprivation treatments. It also suggested that combined androgen blockade—nonsteroidal anti-androgen therapy with an orchiectomy or LHRH analogues—be considered for the treatment of locally advanced or metastatic prostate cancer.
It also stated that a newer nonsteroidal antiandrogen agent, bicalutamide, is preferable to older agents such as flutamide. “New data suggest bicalutamide combined with injection might improve survival by up to 20% and has fewer side effects, such as nausea and night blindness, than the older agents. Physicians should be aware of this,” Dr. Loblaw said.
Still, he said, the struggle continues to distinguish the minority of men who will die from their prostate cancer from the majority of men who will die with it. “We know that prostate cancer kills 40,000 Americans and 4,000 Canadians every year, so we have to be able to separate out the bad actors.” Dr. Loblaw and Canadian coinvestigators recently began accrual to the Early vs. Late Androgen Ablation Therapy (ELAAT) trial in the hope of doing just that.
ELAAT will enroll 11,000 patients who have recurrent prostate cancer after radiation therapy and will randomize them either to immediate hormone treatment or to hormone treatment once their prostate-specific-antigen level reaches 25 ng/mL.
“If men have symptoms after the cancer comes back, they should have hormone treatments. But the PSA when that occurs is around 100 [ng/mL]. So, we are only going to wait until the PSA rises to 25 [ng/mL]. It might be OK to wait, because hormone treatment has so many dangerous side effects,” he said.
'The more we study this, the more aware we become that there are serious side effects associated with the hormones.' DR. LOBLAW