Radiation Improves Outcome After Post-Prostatectomy PSA Recurrence

By Charles Bankhead
BALTIMORE, 18 june 2008-- When men have a biochemical recurrence after a prostatectomy for localized disease, survival improves significantly with salvage radiation, investigators here found.
A retrospective analysis showed a three-fold survival improvement with salvage radiation, Bruce J. Trock, Ph.D., of Johns Hopkins, and colleagues reported in the June 18 issue of the Journal of the American Medical Association.
Adding hormonal therapy to salvage irradiation led to no further improvement in survival.
"These data suggest that men for whom salvage radiotherapy is most beneficial are those with a PSA doubling time of less than six months, who also undergo treatment within two years of an increase in PSA level," the authors said.
"If validated in other settings, these results could motivate a clinical trial comparing adjuvant with salvage radiotherapy, with prostate cancer-specific survival and overall survival as the primary endpoints."
The findings hint at a strategy to address a major clinical conundrum of prostate cancer -- how to manage asymptomatic biochemical recurrence.
From 15% to 40% of men have recurrence within five years of radical prostatectomy. In most cases, the recurrence manifests only in an elevated PSA level. Two-thirds of those recurrences lead to overt metastases if left untreated, leading to the patient's death in most instances.
"For such men it is unknown whether salvage radiotherapy confers a survival benefit compared with observation," the authors said. "Furthermore, it is unknown whether the likelihood of benefit differs for immediate versus delayed salvage radiotherapy, or among subgroups of men defined by pathological attributes."
Further adding to the quandary, two large randomized trials in men with pathologically advanced prostate cancer demonstrated significant improvement in biochemical relapse-free survival and clinical recurrence-free survival with adjuvant radiotherapy. However, neither study showed an improvement in metastasis-free or overall survival.
"These results have sparked debate as to whether all patients with pT3 disease who undergo prostatectomy should receive immediate adjuvant treatment, or whether close surveillance with salvage treatment provided early upon PSA relapse can provide a similar benefit and avoid overtreating men who do not progress," the authors said.
In an effort to eliminate some of the uncertainty, Dr. Trock and colleagues reviewed records on 635 men who had PSA recurrence after radical prostatectomy for localized prostate cancer. There were 397 men who received no salvage therapy, 160 who received salvage radiotherapy alone, and 78 who received salvage irradiation and hormonal therapy.
Median follow-up from recurrence was six years and median follow-up from prostatectomy was nine years. The primary endpoint was prostate cancer-specific survival, defined as the interval from recurrence to death from the disease.
A total of 116 men died of prostate cancer. Of those 89 received no salvage therapy, 18 received salvage radiotherapy, and nine received radiotherapy and hormonal therapy.
Salvage radiotherapy alone was associated with hazard ratio of 0.32 for the primary endpoint compared with men who had no salvage therapy (95% CI, 0.17 to 0.54, P<0.001). Adding hormonal therapy to irradiation led to a hazard ratio of 0.34, which was significantly better than no therapy (P=0.003) but no better than radiotherapy alone.
The improvement in prostate cancer-specific survival was limited to men who had a PSA doubling time of less than six months. Additionally, initiating salvage radiotherapy more than two years after recurrence conferred no advantage over observation. Men whose PSA level never became undetectable after salvage radiotherapy also derived no survival benefit.
Co-author Stephen J. Freedland, M.D., reported serving on the speaker's bureau and advisory boards for AstraZeneca and on an advisory board for GTX Inc. The remaining authors reported no disclosures.
Primary source: Journal of the American Medical AssociationSource reference:Trock BJ, et al "Prostate cancer-specific survival following salvage radiotherapy vs observation in men with biochemical recurrence after radical prostatectomy" JAMA 2008; 299: 2760-2769.