Study Suggests Delaying ADT Until Symptoms Appear Following Primary Prostate Cancer Treatment

Xabier Garcia-Albeniz, MD

A rising prostate-specific antigen (PSA) after surgery or radiation therapy for prostate cancer is not enough reason, on its own, to initiate androgen-deprivation therapy (ADT), a large observational study has found. Rather, survival appears to be the same in these patients whether ADT is given immediately or delayed until symptoms appear or a scan shows cancer, according to the findings announced in a May 12 presscast prior to the 50th Annual Meeting of the ASCO.

Deferred initiation could help delay ADT by 2 or more years for a population of about 60,000 men, according to the authors and ASCO, offering those patients a better quality of life by avoiding common and often debilitating side effects of this type of treatment—sexual dysfunction, osteoporosis and risk of bone fracture, hot flashes, decreased mental sharpness, fatigue, loss of muscle mass, increased cholesterol, weight gain, and depression. Some of those side effects may become more severe the longer a patient is taking ADT.

“Rising PSA levels trigger a lot of anxiety, and many men want to start treatment as soon as possible,” said lead study author Xabier Garcia-Albeniz, MD, a research associate at the Harvard University School of Public Health, in Boston. “These findings suggest that there may be no need to rush to ADT. If our results are confirmed in randomized trials, patients could feel more comfortable waiting until they develop symptoms or signs of cancer that are seen on a scan before initiating ADT.”

Neither ASCO nor the National Comprehensive Cancer Network (NCCN) offers treatment guidelines for the timing of ADT initiation in patients who experience a PSA rise after treatment—a condition known as PSA relapse—but remain asymptomatic and have clear scans, Garcia-Albeniz said. The NCCN has described the question as a “therapeutic dilemma,” the doctor said.

In the study, investigators collected data on 14,000 patients enrolled in a national prospective registry—CaPSURE: Cancer of the Prostate Strategic Urologic Research Endeavor, based at the University of California, San Francisco. Of those patients, 2012 who underwent radical prostatectomy or radiation therapy with cure as a goal subsequently experienced a PSA relapse, defined as PSA ≥0.2 ng/mL or 3 PSA levels taken 1 month apart that show a consistent increase. The researchers considered ADT initiation within 3 months of PSA relapse to be immediate treatment, and defined deferred ADT treatment as beginning 2 years after PSA relapse or upon the emergence of metastasis, symptoms, or a short PSA doubling time.

ADT was defined as orchiectomy or LHRH agonists with or without antiandrogens, Garcia-Albeniz said.

Among the men tracked in the study, PSA relapse occurred a median 27 months after primary treatment, the doctor reported. After PSA relapse, he said, patients were followed for a median 41 months.

Investigators found that estimated 5-year overall survival was roughly the same in the immediate and delayed ADT groups: 85.1% for immediate ADT and 87.2% for delayed ADT. Ten-year overall survival was the same in both groups: 71.6%.

Using deferred ADT as a reference, the hazard ratio for prostate cancer-related mortality in the immediate ADT group was 1.15 (95% CI: 0.33-3.97), Garcia-Albeniz reported.

"Hormone therapy is one of the oldest, most common, and most effective treatment approaches in prostate cancer, and these findings will influence the treatment of thousands of patients worldwide,” said Peter P. Yu, MD, FASCO, ASCO President-Elect. “This study is also a great example of how less aggressive treatment can sometimes offer patients optimal outcomes while sparing them from side effects that impair their quality of life."

Garcia-Albeniz cautioned that the study did not take into account factors including healthy behavior, diet, or blood pressure, which could have skewed results.

To avoid bias, he said, the results should be confirmed via a randomized clinical trial. In fact, he noted, a phase III randomized clinical trial testing immediate vs delayed ADT in men with PSA-only relapse (clinicaltrials.gov reference No. NCT00110162) was initiated in Australia in 2004, and is ongoing.

Until that trial is completed, he said, his team’s observational results are solid enough to be considered by doctors as they treat men in this population.

“This provides really strong support for [conducting a randomized controlled trial] and should put doctors and patients in a position of equipoise,” Garcia-Albeniz said. “This provides comfort if they choose to withhold [immediate] treatment.”

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