Salvage radiotherapy boosts disease-free survival in prostate cancer patients

Treatment inside a two-year window and a prostate-specific antigen doubling time of less than six months may be the key factors in optimizing salvage radiotherapy results for recurrent prostate cancer, according to investigators from the Brady Urological Institute at Johns Hopkins School of Medicine.

Their preliminary results offer evidence that salvage radiotherapy can improve prostate cancer-specific survival after radical prostatectomy.

The study enrolled 635 men who had developed recurrent disease after radical retropubic prostatectomy. A single PSA measurement of 0.2 ng/mL or higher was the criterion for biochemical recurrence, said lead author Bruce Trock, Ph.D, and colleagues in the Journal of the American Medical Association. Conformal radiation to the prostate, seminal vesicle bed, and periprostatic tissues were delivered at a dose of 45 Gy in daily fractions of 1.8 to 2 Gy.

Final analysis was done on 398 of the 635 men. Of those 398, 160 had no salvage therapy, 160 had radiotherapy alone (66.5-Gy median dose), and 78 received salvage radiotherapy (67.2-Gy median dose) plus hormonal therapy. Median follow-up from a diagnosis of recurrence was six years (JAMA 2008;299:2760-2769).

The authors found that men who had salvage radiotherapy and hormonal therapy had a significantly shorter time to recurrence, shorter PSA doubling time, and a higher PSA level at the time of radiation therapy initiation. Men who were not treated with salvage therapy had a higher prevalence of positive lymph nodes.

Trock told Diagnostic Imaging that the improvement in survival was the same for salvage radiotherapy with or without added hormone therapy, although he cautioned that the number of patients who received both treatment regimens was relatively small (78 men). Questions about the timing and duration of hormonal therapy need to be answered.

While the study strongly indicated that men who benefit from salvage radiotherapy must meet both criteria - PSA doubling criteria time of six months and treatment within two years - follow-up time beyond six years may lead to a different outcome, said Trock, who is director of the division of epidemiology at the Brady Urological Institute.

Trock's group will continue to track this cohort and will add more patients to the study group.

"We also plan more research to try to identify biological mechanisms that discriminate those who benefit from radiotherapy from those who don't," he said.

These study results should encourage urologists to send patients for radiotherapy sooner rather than later, said Dr. W. Robert Lee, a professor in the department of radiation oncology at Duke University Medical Center.

"Urologists should understand that in patients with high-risk disease, the addition of radiotherapy, whether adjuvant or salvage, can affect the natural history of the disease by reducing subsequent recurrence, reducing metastatic disease, and improving overall survival," he said.