Postoperative Radiation Therapy Extends Progression-free Survival in Men with High-risk Prostate Cancer


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Postoperative irradiation significantly improves biochemical progression-free survival and local control compared with a “wait-and-see” approach in men with high-risk prostate cancer, according to more than a decade of long-term follow-up in the European Organisation for Research and Treatment of Cancer [EORTC] 22911 trial. These findings, recently published online in The Lancet,1 confirm previously reported 5-year results of the trial. An exploratory analysis suggested that postoperative irradiation might improve clinical progression-free survival in men younger than age 70 years and in those with positive surgical margins, although a detrimental effect was suggested in men aged 70 years or older.

According to lead author Michel Bolla, MD, Centre Hospitalier Universitaire A Michallon, Grenoble, France, these results suggest that younger patients (ie, under age 70) and those with positive surgical margins derive significant benefit from postoperative radiation in terms of biochemical progression-free survival and local control and perhaps in clinical progression-free survival. In contrast, patients aged 70 and older appear not to have a benefit.

“Within the framework of a multimodal approach, the urologist should explain to the patient before radical prostatectomy that immediate irradiation could be applied if the patient has high-risk features, such as extracapsular extension, positive margins, and seminal vesicle involvement. Should the patient not agree, irradiation should probably be postponed until [prostate-specific antigen increase] becomes minimally detectable,” Dr. Bolla added.

Study Design

EORTC 22911 randomly assigned 1,005 men to either a wait-and-see policy (n = 503) or postoperative radiation (n = 502). There was no consistent policy in the wait-and-see group, since not all men received radiation therapy at disease progression. The study population included men who were aged 75 or younger and had undergone radical prostatectomy. The prostate specimens had at least one of the following features denoting high risk: extracapsular extension, positive surgical margins, or seminal vesicle involvement. About 98% had no nodal involvement, and nodal involvement was not considered in the inclusion criteria.

The study was done with contemporary radiation techniques at the time it was initiated. Radiation therapy was given within 16 weeks of surgery at a dose of 50 Gy to the prostate bed in 25 fractions over 5 weeks; a 10-Gy boost was given in 5 fractions over 1-week to a reduced volume. Patients assigned to the wait-and-see arm were treated at biochemical or clinical relapse with irradiation or another treatment.

At a median follow-up of 10.6 years, the rate of biochemical progression was 39.4% in men who received radiation following surgery vs 61.8% in men assigned to the wait-and-see approach (P < .0001). Locoregional relapse occurred in 8.4% of the postoperative irradiation group vs 17.3% of the wait-and-see group. However, the difference in clinical progression-free survival at 5 years of follow-up favoring postoperative irradiation was not maintained after 10 years, and both groups had similar rates of distant metastasis (about 11%) and overall survival (76.9% for postoperative irradiation vs 80.7% for the wait-and-see policy). The 10-year cumulative rate of prostate cancer–related mortality was 3.9% for postoperative irradiation vs 5.4% for the wait-and-see approach.

Unresolved Issues

In an accompanying editorial,2 Jason A. Efstathiou, MD, DPhil, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, noted that the long-term results of this study and other large trials still support the role of adjuvant irradiation in men with prostate cancer, especially those younger than 70 years, with high-risk features such as extracapsular extension, seminal vesicle involvement, and, most importantly, positive margins with acceptable long-term morbidity. However, he suggested there are unresolved issues in this setting that await results of other trials.

These remaining issues include questions about the optimal timing of irradiation (adjuvant vs early salvage), and whether there is a benefit of more aggressive therapy in the salvage setting, such as androgen deprivation therapy in combination with irradiation and/or extending the radiation field to include the pelvic nodes and prostate bed. These questions are being explored in the RADICALS-HD, RAVES, GETUG-17, EORTC 22043, RTOG 9601, and RTOG 0534 trials.

Dr. Efstathiou emphasized the need for a multidisciplinary approach when surgery alone has probably not been curative. “In this setting, prospective data still support postoperative radiation. The onus is on the uro-oncology team [surgical, radiation, and medical] to discuss postoperative radiation with the patient, address optimal timing of initiation when it is used, and to provide justification when it is not.” ■

Disclosure: Dr. Bolla and Dr. Efstathiou reported no potential conflicts of interest.

References

1. Bolla M, van Poppel H, Tombal B, et al: Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: Long-term results of a randomized controlled trial (EORTC 22911). Lancet 380(9858): 2018-2027, 2012.

2. Efstathiou JA: Postoperative radiation for prostate cancer. Lancet 380(9858): 1974-1976, 2012.



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