There is little or no survival benefit to immediate initiation of androgen-deprivation therapy (ADT) versus deferred ADT initiation among prostate cancer patients with prostate-specific antigen (PSA)-only relapse, according to a large study based on data from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database.
The study of 2012 men, presented at the American Society of Clinical Oncology Annual Meeting, was featured in a “presscast” news conference for the media ahead of the meeting (Abstract #5003).
“Rising PSA levels trigger a lot of anxiety, and many men want to start treatment as soon as possible,” said the lead study author, Xabier Garcia-Albeniz, MD, a research associate at Harvard University School of Public Health. “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.”
Garcia-Albeniz said the role of ADT in these patients is not clear. The National Comprehensive Cancer Network guidelines note that this is a therapeutic dilemma, and the ASCO guidelines say the critical issue is to determine whether there is a benefit and how large it is when these patients are asymptomatic.
Deferred initiation was defined as initiation at clinical progression or at least two years after PSA relapse. Androgen-deprivation therapy was defined as orchiectomy or use of luteinzing-hormone-releasing hormone (LHRH) agonists, with or without anti-androgens.
The study was funded by the National Institutes of Health, the University of California at San Francisco, the CaPSURE Program (which is funded in part by an educational grant from Abbott Laboratories), ASISA (a health insurer in Spain), and the Spanish Society of Medical Oncology.
The 2,012 patients, with T3N0M0 disease, had a PSA relapse, defined as greater than 0.2 ng/mL after radical prostatectomy or three rising determinations one month apart after radiotherapy. Exclusion criteria included having ADT in the 12 months before inclusion in the study, metastatic disease as shown by CT scan or bone scan, and symptoms.
Patients were assigned to the “immediate” strategy if they initiated ADT within a three-month grace period of PSA relapse. Patients were assigned to the “deferred” strategy if they initiated ADT in two or more years after PSA relapse or when they presented with metastasis, symptoms or a short PSA-doubling time.
No treatment for PSA relapse other than ADT, such as rescue radiotherapy, was allowed. The median age of the 2,012 patients was 69; 33.8 percent of patients had a Gleason score above 7; 31.8 received radiotherapy as primary treatment; and the median time from primary treatment to PSA relapse was 27 months, with a range of 14 to 51 months.
After relapse, patients were followed a median of 53.2 months.
No Statistically Significant Difference in Outcomes
With deferred ADT as the reference, the all-cause mortality hazard ratio for immediate ADT 0.94, and the prostate-cancer specific mortality hazard ratio was 1.15, Garcia-Albeniz reported.
The five-year all-cause survival rate for deferred ADT was 87.2 percent, versus 85.1 percent for immediate ADT; the 10-year all-cause survival rates for both study arms were identical at 71.6 percent.
The five-year prostate cancer survival rate for deferred ADT was 96.0 percent, versus 93.3 percent for immediate ADT; the 10-year prostate cancer survival rates for deferred ADT was 90.2 percent, versus 89.4 percent for immediate ADT.
Garcia-Albeniz noted that since this was an observational study, there could be differences between the two groups, in baseline characteristics such as Gleason grade at start of therapy, or in longitudinal factors such as healthy behavior, diet, or blood pressure. “The true difference between the compared strategies might differ from this study's findings,” he said.
A truer picture, though, is expected from an ongoing randomized Phase III study in Australia, NCT- 00110162/TROG-0306, which Garcia-Albeniz said is using the same inclusion criteria as his study. “The gold standard is a randomized clinical trial, but this study, while observational, may not change practice but it may help leverage decisions,” he said.
Peter P. Yu, MD, ASCO President-Elect and co-moderator of the presscast, said that 60,000 men in the U.S. face this decision every year. “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,” he said.
ASCO President Clifford A. Hudis, MD, the other co-moderator, added that the study offers strong support for the randomization and should make patients and physicians comfortable with either treatment decision. And the hypothesis that this study would generate is that there is not much difference one way or another, and will provide reassurance for doctors or patients if they choose to hold back on therapy, for quality of life or other reasons.
Patients ‘Fixated on PSA’ Can Be Reassured
Asked for his opinion for this article, Julio M. Pow-Sang, MD, Chairman of Genitourinary Oncology at Moffitt Cancer Center, who was not involved with the study, said the report is reassuring and timely: “Many men are fixated on their PSA—they only want to see how the number goes—and now with this report there is an objective way to discuss delaying treatment with them and reassure them that waiting is fine. We can explain that there are ways to determine when it becomes important to start therapy, such as PSA kinetics or PSA doubling time.”
Pow-Sang said he counsels patients that treatment for prostate cancer is not “all-or-nothing” but rather a range or grade, and that lab tests and close follow-up can help determine whether to treat now or later.