Phase III results of adjuvant radiotherapy (RT) versus "wait and see" (WS) in patients with pT3 prostate cancer following radical prostatectomy (RP) (ARO 96-02/AUO AP 09/95)

Reviewer: Ryan Smith , MD
OncoLink
Last Modified: May 15, 2005

Presenter: T Weigel
Presenter's Affiliation: University Hospital Ulm, ARO
Type of Session: Scientific

Background

A common treatment for patients diagnosed with prostate cancer is a radical prostatectomy, often with excellent results
Disease outside of the prostate (pT3) is often found at surgery, either because this advanced disease was known prior to surgery or because of upstaging at surgery
The role of adjuvant treatment in this situation remains controversial
This study randomized patients with pT3 prostate cancer who had undergone a radiacal prostatectomy to either observation or adjuvant radiation

Materials and Methods

385 men with pT3 were randomized to either observation (n=192) or adjuvant radiation to the prostate bed to a dose of 60 Gy (n=193)
Patients were stratified for Gleason score, margin status, neoadjuvant hormonal treatment, and stage (pT3a+b vs. c)
Primary endpoint was two consecutive PSA rises
Median follow up was 3.3 years, with 4 year results

Results

33 patients randomized to observation received radiation and 32 patients randomized to radiation were observed
78 patients did not achieve an undetectable PSA and were irradiated because of this
Therefore, a total of 108 patients had radiation and 153 patients were observed
biochemical NED rates were 81% in the radiation arm vs. 60% for the observation arm
The rate of late grade 2 rectal toxicity (rectal bleeding) was 3% in the radiation arm
Overall survival rates were similar in both groups

Author's Conclusions

Adjuvant radiation for pT3 patients after radical prostatectomy significantly reduces biochemical relapses
The rate of toxicity from this adjuvant radiation was very low

Clinical/Scientific Implications
The biggest critiques of this study is that the data needs to mature in order to be accepted and that with the switching between the treatment groups that was done, the groups may not be balanced. This study echoes the results of the EORTC study presented at ASCO 2004. Specifically, that the progression free survival was improved by a rate of approximately 20%, with mild increases in both grade 1 and 2 toxicities, with rates of grade 3 toxicities being <5%. However, in both studies, there was not yet an effect on overall survival. In the AUA 2005 meeting, there will be an additional study presented by the SWOG group, again with an approximate 20% increase in relapse free survival. 10 year overall survival was 74% vs. 63%, yet not statistically significant. Therefore, there continues to be debate over the optimal treatment in pT3 patients following radical prostatectomy. It should definitely be considered, especially with seminal vesicle involvement or detectable PSA, but without an overall survival benefit, it is difficult to change the standard of care for all pT3 patients after radical prostatectomy from careful observation.