Preliminary results of RTOG 96-01 in progressive prostate cancer


RTOG 96-01 is a randomized, multi-center Phase III trial designed to compare bicalutamide monotherapy + salvage radiation therapy  to a placebo + salvage radiation alone in men with pT2-3N0Mo prostate cancer who have an elevated PSA after surgery. The initial results of this trial were presented by Heney et al. at the annual meeting of the Society for Urologic Oncology in Bethesda last week. 

Eligible patients needed to be clearly identified as having no indication of metastatic disease but to have a sustained or a rising PSA following their initial surgery. The full trial protocol is available on the ClinicalTrials.gov web site. Patients were stratified by time of recurrence, whether they had received neoadjuvant androgen deprivation prior to their surgery, and their PSA level at time of enrollment. (Neoadjuvant androgen deprivation was not uncommon prior to surgery in the mid to late 1990s, but has since been abandoned as clinically ineffectual.) The primary endpoint for this study is overall survival (which has not yet been achieved).

What is very important to note is that patients were treated with bicalutamide for 2 years, but with a dose of 150 mg/day, which is a dose level that has been associated with significant risk for cardiovascular side effects. In the USA bicalutamide has only been approved for treatment of prostate cancer at a dose of 50 mg/day.

The preliminary results of this trial, as presented by Heney et al., are as follows:

  • 771 eligible patients were enrolled and randomized to either salvage external beam radiation therapy (EBRT) + a placebo or EBRT + bicalutamide.
  • Average (median) follow-up was 7.1 years.
  • The failure rates (established by clear evidence of distant metastasis) in the two arms of the trial were
    • 7.4 percent in the EBRT + bicalutamide arm
    • 12.6 percent in the EBRT + placebo arm
  • Rates of freedom from biochemical progression were
    • 57 percent in the EBRT + bicalutamide arm
    • 40 percent in the EBRT + placebo arm
  • Gynecomastia was more evident among patients in the EBRT + bicalutamide arm of the study.

It appears that these benefits were not affected by surgical margin status or by whether the patients’ Gleason scores were above or below 6. However, the benefits are reported to have been most pronounced in patients with Gleason scores of 8 to 10.

As stated above, the patients will continue to be followed to see if a true overall survival benefit can be demonstrated, but whether a 50 mg dose of bicalutamide can demonstrate the same impact remains unknown.

2 Responses

  1. If I am reading the results correctly, they mean that salvage radiation has only limited success rate (40% freedom from biochemical failure) after biochemical failure post-prostatectomy. Are there any studies presenting a different outcome?

  2. Reuven:

    There are other data but they are difficult to compare on an apples to apples basis. My impression would be that an overall 40% progression-free survival rate at 7 years after salvage EBRT would be of generally the correct order of magnitude for patients initially diagnosed and treated surgically back in the mid 1990s.

    Remember (a) that men with higher risk do better with a combination of EBRT and androgen deprivation using an LHRH agonist and an antiandrogen and that (b) men being diagnosed today might still have pT2-T3N0M0 disease aftyer surgery but a lower tumor load and therefore a lower risk for aggressive extracapsular disease. Radiation alone may only be appropriate for relatively low-risk patients with a longer PSA doubling time.

    The fact that it takes so long to do these studies and that they rarely compare apples to apples makes exact comparisons difficult in the extreme.

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