Postoperative radiotherapy after radical prostatectomy significantly improves biochemical progression-free survival and local control

A clinical trial conducted by the EORTC Radiation Oncology and Genito-Urinary Groups and reported in The Lancet suggests that postoperative radiotherapy (P-RT) following radical prostatectomy (RP) significantly improves biochemical progression-free survival (BPFS) and local control. Exploratory analyses also suggest that P-RT might improve clinical progression-free survival (PFS) in patients younger than 70 years of age and in patients with positive surgical margin. However, P-RT might have a possible detrimental effect in patients 70 years or older.

In prostate cancer, so long as the cancer is confined to the prostate, RP provides good long-term local control and survival. However, in cases where the cancer extends beyond the prostatic capsule, the risk of local failure increases, and unfortunately, extraprostatic disease and positive surgical margins are common after RP.

In EORTC trial 22911, patients aged 75 years or younger with positive surgical margin or pT3 prostate cancer were randomized to P-RT (503 patients) or wait-and-see (WS, 502 patients) until biochemical failure based on prostate specific antigen levels. Upon biochemical or clinical progression, patients in the WS arm were to receive RT or hormone therapy depending upon whether the relapse appeared localized or systemic.

At 10.6 years median follow-up, this study showed that P-RT significantly improves BPFS (HR=0.49, 95%CI: 0.41-0.59, p<0.0001) and locoregional control (HR=0.45, 95 %CI: 0.32-0.68, p<0.0001). The impact of P-RT on clinical PFS was not statistically significant (HR=0.81, 95%CI 0.65-1.01, p=0.0539) which does not confirm the data published in The Lancet in 2005 with 5-year median follow-up.

Dr. Collette, of the Statistics Department EORTC Headquarters in Brussels, Belgium, says “These results were very intriguing especially since they appeared somewhat discordant with those of the similar study conducted by Southwest Oncology Group (SWOG). We were keen to explore the data further to better understand what was going on. We saw that the control group of the SWOG study had a much worse survival than that of our study, which could explain why they show a benefit of post-operative irradiation in terms of survival, while we do not. We also investigated subgroups of patients to see if the treatment effects depended on some patient factors.”

For all endpoints, the treatment effect seemed to vary according to patient age and surgical margin status suggesting that P-RT might negatively impact on clinical PFS and overall survival in patients aged 70 years or older (HR=1.78, 95%CI 1.14-2.78, p=0.012 and HR=2.94, 95%CI 1.75-4.93, p<0.001, respectively). The risk of distant metastases (HR=0.99, 95%CI: 0.67-1.44, p=0.9375) and overall survival (HR=1.18, 95%CI: 0.91-1.53, p=0.2004) were not significantly different.

Professor Bolla, of the Department of Radiation Oncology at the Centre Hospitalier Universitaire A Michallon in Grenoble, France, and lead author of the study, says, “These data suggest that before surgery it is desirable that the surgeon explain to the patient, that should there be poor prognostic factor(s) mentioned on the pathological report, the advisability of a post-operative radiation therapy might be discussed within the frame of a multidisciplinary approach.”

John Bean

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