Post-Operative Radiotherapy (P-XRT) After Radical Prostatectomy (Px) Improves Progression-Free Survival (PFS) in pT3N0 Prostate Cancer (PC) (EORTC 22911)

Reviewer: John Wilson, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 5, 2004

Presenter: M Bolla
Presenter's Affiliation: Radiotherapy, Centre Hospitalier Regional de Grenoble-La Tronche, Grenoble, France
Type of Session: Scientific

Background

Radical Prostatectomy is a definitive treatment option for patients with low-risk, clinically staged T1-2N0M0 prostate cancer, where the cancer appears confined to the prostate
Pathological results after surgery sometimes show high risk features, such as capsule invasion, positive surgical margins, and seminal vesicle invasion
The is controversy whether immediate radiation treatment is effective in preventing cancer recurrence if these features are found, or if it is better to wait until the PSA rises
The EORTC (European Organization for Research and Treatment of Cancer) initiated a randomized trial to assess the value of postoperative radiotherapy for patients with these high risk pathological features

Materials and Methods

Eligibility criteria included age of 75 years or younger, with WHO (World Health Organization) performance status of 0-1, and preoperative clinical stage T0-3N0M0 prostate cancer
Patients also needed at least one of the following pathological risk factors: capsule invasion, positive surgical margins, or seminal vesicle invasion
Patients were stratified by institution as well as pathological status of their seminal vesicles, prostate capsule and surgical margins
Patients were randomized to (P-XRT) or (WAWA) watchful waiting until local failure occurred
Radiation treatment consisted of 60 Gy over 6 weeks within 4 months of prostatectomy
The primary objective of the trial was to detect a difference of 7.8% in the 5 year clinical or biological PFS (progression free survival)
Secondary objectives included local control, overall survival, acute toxicity, and late morbidity.

Results

1005 patients were entered onto the trial, with most of them (597) coming from Belgium
The median age was 65.4 years, and almost all (93.8%) had an excellent performance status of zero
The median preop and postop PSA was 12.3 and 0.2 ng/ml
Most patient were clinical stage T2 (65%) and pathologic WHO grade 2/3 (63%)
41 pts randomized to radiation did not receive it, and only 5 patients randomized to watchful waiting received radiation
Most of the patients had either capsule penetration alone or capsule penetration and positive margin
The biochemical PFS (progression free survival) was defined as the time to 2 PSA increases over nadir, first clinical failure, or death, and at 5 years it was better in the P-XRT group, 72% versus 52%, p<0.0001
Clinical PFS was also better in the P-XRT patients, 83.3 vs 74.8%, p=0.004
There was an increased risk of grade 1-2 immediate and late side effects, and grade 1 or greater late effects were also increased with P-XRT, being 68 vs 54% at 5 years
Grade 3 side effects were less than 5% in each group
There was some suggestion of greater late genitourinary toxicity with larger field sizes (larger than 9x9 cm)

Author's Conclusions

Post-operative radiotherapy results in improved biochemical and clinical PFS, which needs to be balanced with treatment side effects
Further follow-up is needed to assess impact on distant metastases and overall survival, since more than 90% of patients are still alive

Clinical/Scientific Implications
Dr Bolla presents here a large, well done, randomized study assessing the value of post-prostatectomy radiation based on high-risk pathological features. There is a clear benefit from radiation in terms of increasing biochemical and clinical progression free survival. However, since there is only a median follow up of 5 years, and more than 90% of patients were alive at the time of statistical analysis, longer follow-up is needed to see if the treatment produces an overall survival benefit as well. The distant metastasis rate may also show a difference with longer follow-up. There was a slightly higher rate of low grade acute and late side effects which needs to be balanced with the early promising results of this study. What was not discussed in this presentation was what treatment the patients in the control group received after they developed local failure, which hopefully will be elucidated when this study is published.