Hormone Therapy Delay Fails to Decrease Prostate Cancer Patients’ Quality of Life, Study Reports

Hormone Therapy Delay Fails to Decrease Prostate Cancer Patients’ Quality of Life, Study Reports

After treating a man for prostate cancer, doctors pay close attention to whether levels of the disease’s main biomarker begin rising — an indication that the cancer has returned.

Rising levels of PSA — or prostate specific antigen — prompt many doctors to prescribe androgen deprivation therapy as a follow-up treatment. Prostate cancer requires androgen hormones such as testosterone to grow, and androgen deprivation therapy suppresses hormone production.

Conventional wisdom would suggest that the sooner androgen deprivation therapy is started, the better. And an Australian study indicated that men do survive longer when treated early.

But men whose prostate cancer has relapsed or have an incurable form of the disease have the same overall quality of life whether treatment begins right away or is delayed two years, the researchers said. And men’s sexual function is worse when the therapy is started immediately, they added. This and other findings prompted the team to wonder if some men would rather opt for a better quality of life than a longer life.

After combing through the results of a Phase 3 clinical trial, the researchers concluded that patients’ quality of life is the same whether they receive androgen deprivation therapy as soon as PSA levels begin rising or wait two years.

Weighing against immediate application of the therapy was a finding that it may impair sexual activity and generate unpleasant treatment-related consequences.

The study covered both men with rising PSA levels but no other signs of relapse and men with a symptom-less but incurable form of prostate cancer. Published in the journal The Lancet Oncology, it appeared to support the notion that early treatment is preferable in this patient group — particularly since the initial analysis of the trial data linked immediate treatment to longer survival.

But both the study and a related commentary underscored the importance of doctors looking at individual patient and disease characteristics before deciding whether to recommend immediate or delayed treatment.

A team at the Peter MacCallum Cancer Center in Melbourne led the study. It was titled Health-related quality of life for immediate versus delayed androgen-deprivation therapy in patients with asymptomatic, non-curable prostate cancer (TROG 03.06 and VCOG PR 01-03 [TOAD]): a randomised, multicentre, non-blinded, phase 3 trial.”

The Phase 3 TOAD trial (NCT00110162) explored quality of life linked to treatment. Since none of the men in the study had symptoms of the disease, researchers argued that some might prefer better quality of life over longevity.

“When such a patient is asymptomatic, it is particularly important that the risk–benefit ratio of any treatment offered is taken into account when deciding when and how to treat,” they wrote.

The 293 men in the study were randomly assigned to receive androgen deprivation therapy as soon as  their PSA levels began rising, or two years later, provided that their condition did not worsen.

One hundred forty-two received immediate treatment and 151 delayed treatment. The initial trial analysis showed that 91.2 percent in the immediate therapy group were still alive after five years, compared with 86.4 percent in the delayed treatment group.

The second analysis showed no difference between the groups in health-related quality of life. Five years after androgen deprivation therapy, researchers found no statistical differences in patients’ overall quality of life, physical functioning, emotional functioning, fatigue, shortness of breath, insomnia, and a feeling that they were less masculine.

Men who received immediate treatment reported less sexual activity in the first two years of the study. They also experienced more hormone treatment-related symptoms, particularly hot flushes and nipple and breast enlargement or soreness.

While the difference in sexual activity among the groups was statistically significant, the magnitude of other treatment-related symptoms fell short of significance.

Dr. Fred Saad of Canada’s University of Montreal Hospital Center noted in a commentary that it was reassuring that differences in the groups’ quality of life were small. But he said that “as clinicians, we are still obliged to be attentive to those who are severely affected by androgen deprivation therapy.”

“Individual patients need to be counseled on the undeniable fact that some will experience more profound detriments in quality of life than others,” he said.

More research that allows physicians to understand factors that can predict harsh declines in quality of life or disease progression could help doctors recommend treatment decisions, the team concluded.