ART or SRT in high-risk patients post-surgery?


As many of our regular readers will know, there is no clear answer to the question whether, among men at elevated risk of progressive disease after first-line surgery, it is better to have adjuvant radiation therapy (ART) within a few months of surgery or to wait until salvage radiation therapy (SRT) is clearly advisable.

Although other trials have sought to resolve this question in the past, there have been problems of differing types with almost all of those trials.

Pearse et al. have recently discussed the ongoing implementation of a new trial (the Radiotherapy-Adjuvant Versus Early Salvage or RAVES trial), which is designed to address this problem and is recruiting patients in Australia and New Zealand. This is a randomized, Phase III “non-inferiority” trial intended to see whether observation with early SRT is, in fact, “non-inferior” to immediate, standardized treatment with ART in men with pT3 disease and/or positive surgical margins after radical prostatectomy.

Eligible patients must have had a radical prostatectomy after a diagnosis of adenocarcinoma of the prostate; they must have a PSA level of ≤ 0.10 ng/ml post-surgery (i.e., an “undetectable” PSA level; and they must have at least one of the following, recognized risk factors:

  • One or more positive surgical margins
  • Extraprostatic extension
  • Seminal vesicle involvement

The trial is scheduled to enroll and randomize 470 patients who will receive either “standardized” ART (64 Gy in 32 fractions to the prostate bed) which must be initiated within ≤ 4 months after the radical prostatectomy or close observation with early SRT triggered by a PSA level of > 0.20 ng/ml.

The primary trial endpoint is biochemical failure, as indicated by a PSA level of ≥ 0.4 ng/ml and rising following radiation therapy. A wide variety of secondary endpoints has also been identified and these are all identified on the ClinicalTrials.gov web page for the RAVES trial.

The trial management team claim to have implemented a “rigorous” process of investigator credentialing and a quality assurance program designed to optimize a process of consistent delivery of radiation therapy to all patients.

As of October 31, 2013, the trial had already enrolled 258 patients, and so it seems highly likely to be fully enrolled by the end of 2014 or some time in 2015 at the very latest. The trial is expected to report results no later than some time in 2020.

It seems highly likely to The “New” Prostate Cancer InfoLink that close observation + SRT is, in fact, “non-inferior” to immediate ART for all but the highest-risk patients. The question that this study may still not be able to resolve is how to identify those highest-risk patients who might benefit from immediate ADT. One is tempted to suggest that they are the men with at least two and possibly all three of the recognized risk factors identified above, and that these are the patients who are most likely to benefit from a combination of 3-6 months of neoadjuvant androgen deprivation therapy as well as immediate ART. Maybe the RAVES trial will be able to move us closer to resolving some of these issues.

One Response

  1. If I were to bet ~ I would guess that there is minimal gain for the stage pT3a guys and significant gain for the pT3b guys. Stanford and Harvard already have good data on this with adjuvant hormonal ablation. I think that this study is attempting to see if going without ADT is also beneficial.

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