Benefits of RT Immediately After Prostate Cancer Surgery

Giving radiotherapy immediately after prostate cancer surgery is beneficial (particularly in some subgroups), but it remains unclear whether immediate radiotherapy is preferable to salvage radiotherapy.

These findings come from the long-term follow-up (median, 10.6 years) of the European Organization for Research and Treatment of Cancer (EORTC) 22911 study, and were published online October 19 in the Lancet.

In this trial, 1005 men with high-risk prostate cancer who had undergone radical prostatectomy were randomized to receive immediate postoperative external irradiation or to receive subsequent treatment (radiation or other) only at biochemical or clinical relapse (wait-and-see policy).

The 10-year results show a significant improvement in biochemical progression-free survival in the immediate group, compared with the wait-and-see group (61.8% vs 39.4%; hazard ratio, 0.49; P < .0001). The immediate group also had significantly better locoregional control, so were less likely to need hormonal therapy, the researchers report.

However, in contrast to the results reported after 5 years of follow-up, after 10 years, the results were no longer significant for clinical progression-free survival, distant metastases, or overall survival. At 10 years, overall survival was 76.9% in the immediate group and 80.7% in the wait-and-see group, and cumulative rates of distant metastases were 10.1% and 11.0%, respectively.

Late adverse events were more frequent in the immediate group than in the wait-and-see group (70.8% vs 59.7%; P = .001).

The researchers, headed by Michel Bolla, MD, from the Centre Hospitalier Universitaire A Michallon in Grenoble, France, note that the improvement in biochemical progression-free survival and local control with a wait-and-see policy is "in agreement" with results from 2 other phase 3 clinical trials: the German Arbeisgemeinschaft Radiologische Onkologie (ARO) trial (J Clin Oncol. 2009;27:2924-2930); and the American Southwest Oncology Group (SWOG) 8794 trial (J Urol. 2009;181;956-962).

However, they also note that, unlike their 10-year results, long-term follow-up in the SWOG trial did find a significant difference in overall survival and distant metastases. Dr. Bolla and colleagues suggest that this might be because of the large difference in the wait-and-see groups between the SWOG trial and their EORTC trial (66.0% vs 80.7%). In their trial, salvage treatment was initiated in the wait-and-see group at a lower concentration of prostate-specific antigen than in the immediate group.

Benefit in Specific Patient Groups 
 
Dr. Bolla and colleagues suggest that postoperative radiation might not be the best approach for all patients. "Exploratory analyses suggest that postoperative radiotherapy might improve clinical progression-free survival in patients younger than 70 years and in those with positive surgical margins, but could have a detrimental effect in patients aged 70 years or older," they write.
This sentiment is echoed in an accompanying comment by Jason Efstathiou, MD, from the Department of Radiation Oncology at the Massachusetts General Hospital, Harvard Medical School, Boston.

The results from this EORTC update still support the use of postoperative irradiation in patients younger than 70 years and in those with positive margins, Dr. Efstathiou writes.

"When surgery has probably not cured a patient, prospective data still support postoperative radiation," Dr. Efstathiou concludes. The long-term morbidity and quality of life seem acceptable, and morbidity is probably lower than with systemic alternatives, especially because postoperative radiation reduces the need for future androgen-deprivation therapy, he adds.

However, questions remain, he notes.

In this EORTC trial, as well as in the SWOG trial, the salvage radiotherapy that was given in the wait-and-see group was often delivered too late, Dr. Efstathiou explains. "Hence, these 2 studies are probably better characterized as having compared adjuvant or early salvage with late or no salvage radiation," he writes.

It is hoped that ongoing randomized trials — including the Radiotherapy and Androgen Deprivation in Combination After Local Surgery-Hormone Duration (RADICALS-HD), Radiotherapy Adjuvant Versus Early Salvage (RAVES), and Groupe d'Etude des Tumeurs Uro-Génitales (GETUG-17) — will establish the optimum timing of postoperative radiation (immediate adjuvant vs early salvage), he notes.