Although several large, well-controlled, randomized studies support the use of adjuvant radiation therapy (RT) in all men with T3 disease following radical prostatectomy, none of these studies show significant overall survival benefits. This raises the question of whether physicians should employ this therapy more selectively.
Scottsdale, AZ-Although several large, well-controlled, randomized studies support the use of adjuvant radiation therapy (RT) in all men with T3 disease following radical prostatectomy, none of these studies show significant overall survival benefits. This raises the question of whether physicians should employ this therapy more selectively.
"We have clear evidence that those patients who receive radiation early have improved 5- and 10-year freedom from recurrence and PSA failure. There's some suggestion, but not statistical proof, that their survival will be improved. The data are too strong to ignore."
More important, several large, multi-institutional, randomized, controlled studies have been published in recent years that have shown advantages for using adjuvant RT.
For example, in the 1,000-patient European Organisation for Research and Treatment of Cancer (EORTC) 22911 trial, adjuvant RT showed advantages over active surveillance in terms of PSA progression-free survival (74% vs. 53%, respectively), clinical progression-free survival, and, to a lesser extent, metastasis-free survival, all at a median follow-up of 5 years (Int J Radiat Oncol Biol Phys 2004; 60 [suppl 1]: A-93, S186).
In the Southwestern Oncology Group (SWOG) 8794 trial, PSA progression-free survival at 10 years was 71% in radiation-treated patients versus 44% for men followed with active surveillance (Urology 2004; 6:982-96).
Nevertheless, questions remain regarding the proper adjuvant RT dose. Most studies that have explored this issue have shown that higher doses mean better control rates, Dr. Beyer said.
"That is true in the postoperative setting, where the conventional doses that I was taught to use 20 years ago have been shown to be too low," he said.
However, physicians do not yet know whether doses above 70 Gy are better or even safe in this population.
For now, the strongest indications for adjuvant RT are in post-prostatectomy patients with normal PSA and either extracapsular extension, positive margins, or seminal vesicle involvement, each of which were inclusion criteria for the SWOG and EORTC studies, Dr. Beyer added.
"Gleason scores might make a difference, but that's not as clear," he said.
David I. Quinn, MBBS, PhD, chief of genitourinary medical oncology and medical director of the Norris Cancer Hospital and Clinics, University of Southern California's Keck School of Medicine, Los Angeles, disagreed. He noted that because evidence of increased survival for patients undergoing adjuvant RT remains elusive, the EORTC and SWOG studies show benefits through proxies, such as delay in PSA rise and, more important, though clinical progression.
The initial EORTC study was designed for overall survival, but it did not reach that endpoint, he told Urology Times.
The SWOG study also showed that early adjuvant RT had a significant effect on PSA relapse and recurrence-free relapse, but it did not have a significant effect on overall survival, despite a median follow-up of more than 10 years. This study did show, however, that adjuvant RT significantly delayed patients' need for hormone replacement therapy, which, Dr. Quinn said, is very important because HRT carries many morbid side effects.
"But, at best, it's a very wishy-washy endpoint," he said.