Delaying the start of androgen-deprivation therapy may be a safe option for men with recurrent prostate cancer marked only by a rise in prostate-specific antigen, investigators report.
Among 2012 men with a prostate-specific antigen (PSA)-only relapse following radical prostatectomy or definitive radiation therapy, the estimated 5-year overall survival for men who deferred androgen-deprivation therapy (ADT) for at least 2 years was 87.2%, compared with 85.1% for men who started on ADT within 3 months of a rising PSA measure, a difference that was not significant, said Dr. Xabier Garcia-De-Albeniz, a research associate at the Harvard School of Public Health in Boston.
“Up to now, we have not had clear evidence, or some evidence, that delaying treatment until there are more objective signs of disease is a safe thing to do, so this study will now provide us information to have a dialogue between doctors and patients about whether they should start immediate hormone therapy or whether continued observation and waiting might be a better approach,” said Dr. Clifford Hudis at a media briefing highlighting studies to be presented at the American Society of Clinical Oncology (ASCO) 2014 annual meeting in Chicago from May 30 through June 3.
Dr. Hudis, president of ASCO and chief of the breast cancer service at Memorial Sloan-Kettering Cancer Center, New York, comoderated the briefing but was not involved in the study.
There are currently no widely accepted guidelines regarding the best time to start ADT in men with relapsed prostate cancer signaled only by a rise in PSA, with no evidence of recurrent or metastatic disease on imaging.
Dr. Garcia-De-Albeniz noted that ASCO guidelines state “the critical issue is to determine whether there is benefit and how large it is for starting ADT while patients are asymptomatic,” and that National Comprehensive Cancer Network (NCCN) guidelines refer to a “therapeutic dilemma regarding the role of ADT.”
To see whether men with PSA recurrence could be safely spared for a time from the adverse effects of ADT – hot flashes, sexual dysfunction, fracture risk, fatigue, loss of mental acuity, weight gain, depression, etc. – the investigators combed through records from the prospective Cancer of the Prostate Strategic Urologic Research Endeavor (CAPSURE) registry.
Of the more than 14,000 men whose records are included in the database, 2012 had a PSA relapse after therapy with curative intent.
The authors defined PSA relapse as more than 0.2 ng/mL increase in PSA, or three rising determinations 1 month apart. They determined immediate ADT therapy to be treatment within 3 months of PSA relapse, and deferred therapy as ADT started 2 years or more after PSA relapse was first diagnosed or when patients presented with either metastatic disease, symptoms, or a short PSA doubling time (the length of time was not specified).
ADT could be either orchiectomy or the use of a lutenizing hormone–release hormone agonist with or without antiandrogen agents.
As noted before, the investigators found that there was no significant survival advantage to the immediate ADT treatment strategy. After a median follow-up of 41 months, there were 176 deaths, 37 of which were attributable to prostate cancer. The estimated 5-year overall survival was 87.2% for the deferred ADT group, compared with 85.1% for the immediate treatment group. The respective 10-year estimated survival rates were identical, at 71.6%
Similarly, there was no difference in prostate cancer–specific survival, with 5-year rates of 96% and 93.3%, respectively, and 10-year rates of 90.2% and 89.4%.
Dr. Garcia-De-Albeniz acknowledged that because it was an observational rather than randomized study, it is not possible to rule out other, unrecorded characteristics that might have contributed to overall survival, such as differences in blood pressure control, lifestyle choices, and comorbidities.
He noted that there is an ongoing, randomized, phase III trial examining the question of timing of intervention with ADT in men with rising PSA.
The study was supported in part by the National Institutes of Health, ASISA, SEOM (Sociedad Española de Oncología Médica) and an independent educational grant from Abbott. Dr. Garcia-De-Albeniz reported having no financial disclosures.