Nick Mulcahy

May 15, 2014

Clinicians who delay prescribing androgen-deprivation therapy (ADT) to men with a biochemical recurrence of prostate cancer might be doing the right thing — in more than one way.

It is obvious that delaying ADT prevents unpleasant and debilitating adverse effects, such as sexual dysfunction, bone loss, and muscle mass loss. But a new study indicates that a strategy of delay does not have a negative impact on survival, which has been an unknown.

The study evaluated registry data on 2012 men who had a biochemical relapse after having undergone radical prostatectomy or radiation therapy with curative intent. They were analyzed as having received immediate or delayed ADT.

Estimated 5-year overall survival was not significantly different in the immediate and delayed groups (87.2% vs 85.1%), and estimated 10-year overall survival was the same in the 2 groups (71.6% vs 71.6%), reported lead investigator Xabier Garcia-Albeniz, MD, from the Harvard University School of Public Health in Boston.

He spoke at a presscast held in advance of the 2014 Annual Meeting of the American Society of Clinical Oncology®, where results from the observational study will be presented.

Deaths from prostate cancer were also similar at 5 and 10 years.

"These findings suggest that there may be no need to rush to ADT," Dr. Garcia-Albeniz said in a press statement. The findings could affect about 60,000 men a year in the United States.

ADT was defined as orchiectomy or antiandrogen therapy and/or luteinizing hormone-releasing hormone agonist therapy.

Delayed ADT was defined as starting the hormone therapy 2 years or more after prostate-specific antigen (PSA) relapse or at the time of metastasis, symptoms, or a very short PSA doubling time. Immediate ADT was defined as starting hormone therapy within 3 months of PSA relapse.

A relapse or biochemical recurrence was defined as an increase in PSA of more than 0.2 ng/mL or 3 elevated PSA levels 1 month apart.

All the men had stage I or II disease and no lymph node involvement or metastases. Median follow-up was 41 months.

The results are very reassuring.

"The results are very reassuring — especially for patients and their families," said Julio Pow-Sang, MD, chair of the Department of Genitourinary Oncology at the H. Lee Moffitt Cancer Center in Tampa, Florida, who was not involved in the study.

"It's becoming apparent that starting ADT earlier is not going to make a difference with regard to progression of the cancer," he told Medscape Medical News in an interview.

Dr. Pow-Sang said that "most urologists" wait to start ADT after a biochemical recurrence to see what the PSA will do.

Agreed, said Elizabeth Plimack, MD, a medical oncologist at the Fox Chase Cancer Center in Philadelphia, who was also not involved with the study.

"We usually delay ADT in patients with long PSA doubling times and no evidence of metastases on imaging," she told Medscape Medical News.

The strategy can be carried out with some confidence, she explained. "Nobody ever died from an elevated PSA without evidence of disease spread on a scan."

Nevertheless, the results are "meaningful" because they fill an information void, she said.

Confirmation Coming? Phase 3 Trial Underway

"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," said Dr. Garcia-Albeniz.

The parameters in the current study are the same as those in an ongoing phase 3 trial being conducted in Australia, he added. That trial will eventually serve as the gold standard for clinicians, he said.

In their study, Dr. Garcia-Albeniz and colleagues evaluated national prospective registry data from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), which is based at the University of California, San Francisco.

In the cohort of more than 2000 men with PSA relapse after definitive treatment, median age was 69 years. In addition, 33.8% had a Gleason score above 7, 31.8% received radiotherapy as primary treatment, and median time from primary treatment to PSA relapse was 27 months.

For immediate ADT, the all-cause mortality hazard ratio (HR) was 0.94 (95% confidence interval [CI], 0.51 - 1.73), and the prostate-cancer specific mortality HR was 1.15 (95% CI, 0.33 - 3.97). Neither was statistically significant.

The study was supported by the National Institutes of Health, the Sociedad Española de Oncología Médica, and an independent educational grant from Abbott. Dr. Garcia-Albeniz, Dr. Pow-Sang, and Dr. Plimack have disclosed no relevant financial relationships.

2014 Annual Meeting of the American Society of Clinical Oncology. Abstract 5003. To be presented June 1, 2014.


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