Important updates to older radiotherapy studies from the ASTRO meeting

The following commentary provides updated data on two older but important studies of androgen deprivation therapy + radiation therapy in the treatment of locally advanced and progressive forms of prostate cancer.

EBRT with 2 years of ADT better than 4 months in patients treated for locally advanced prostate cancer

It will come as no surprise that long-term androgen deprivation therapy (ADT) improved outcomes among men treated for locally advanced prostate cancer with external beam radiation therapy (EBRT). While this study is largely irrelevant now because a more recent study, DART 01/05 (discussed here), proved much the same thing with dose escalation, data from a study reported at the recent ASTRO meeting also included pelvic lymph node treatment and has a median of 20 years of follow up.

The final results of RTOG 0902 were reported at ASTRO by Lawton et al. and in a news release. In this multi-institutional study, 1,992 patients were treated between 1992 and 1995. They were all high risk (T2c-T4) with no detectable distant metastases and PSA levels of < 150 ng/ml. All patients were treated according to the following protocol:

  • 44 to 46 Gy to the pelvic lymph nodes
  • 65 to 70 Gy to the prostate
  • The short-term ADT group (STADT) received 4 months of flutamide and goserelin, starting 2 months before EBRT.
  • The long-term ADT group (LTADT) received 24 additional months of goserelin.

At 15 years after treatment:

  • Disease-free survival was 16 percent for the LTADT group vs. 10 percent for the STADT group, and was statistically significant.
  • PSA increase was 45 percent for the LTADT group vs. 61 percent for the STADT group, and was statistically significant.
  • Local progression was 13 percent for the LTADT group vs. 23 percent for the STADT group, and was statistically significant.
  • Distant metastasis rate was 17 percent for the LTADT group vs. 26 percent for the STADT group, and was statistically significant.
  • Disease-specific survival was 10 percent higher for the LTADT group vs. the STADT group, and was statistically significant.
  • Overall survival was 30 percent for the LTADT group vs. 27 percent for the STADT group, and was not statistically significant.
  • No difference in urinary toxicity and minimal difference in bowel toxicity between the two groups.

While all the survival numbers are very low in both groups, it should be recalled that the radiation dose received back then was well below the dose now considered curative. Also, most of such men would now be diagnosed at a much earlier stage of disease progression. There was a clear benefit to long-term compared to short-term androgen suppression, and DART 01/05 proved that the benefit was still true with dose escalation in high-risk patients.

Anti-androgen therapy enhances outcomes of salvage radiation

Two years of anti-androgen therapy improved survival in patients treated with salvage radiation. This report represents an update with over 12 years of median follow-up. The results with 7 years of follow-up were previously reported here.

The results of the randomized clinical trial RTOG 96-01 were also presented by Shipley et al. at the recent ASTRO meeting and reported in a press release. Between 1998 and 2003, 761 patients were treated at multiple sites across the US and Canada. All patients had biochemical recurrence and either stage pT2 with a positive margin or stage pT3, without lymph node involvement or metastases. All patients received 64.6 Gy of EBRT in 1.8 Gy increments (36 fractions), and either 24 months of bicalutamide (150 mg) or a placebo. After 12.6 years median follow up, the anti-androgen had the following effects:

  • Reduced tumor progression and the incidence of local re-growth
  • Reduced rate of metastases — from 23 percent to 14 percent
  • Reduced death from prostate cancer — from 7.5 percent to 2.3 percent
  • Improved overall survival at 10 years — from 78 percent to 82 percent (p = 0.04)
  • Gastrointestinal and/or genitourinary toxicities were low and similar in both arms.
  • Gynecomastia was common with bicalutamide.

While the salvage radiation dose delivered in this study falls short of the 70 Gy now considered adequate, it does provide evidence of a survival benefit linked to added hormone therapy. Another randomized clinical trial, GETUG AFU-16, proved that even a short course of ADT significantly improved progression-free survival when used with salvage radiation, but longer follow-up will be necessary to prove a benefit in prostate cancer survival. RTOG 96-01 proves that prostate cancer-specific survival is indeed improved by the combination of hormone therapy with salvage radiation, although the benefit may be limited to those with lower PSA and negative margins.

Editorial comment: This commentary was written by Allen Edel for The “New” Prostate Cancer InfoLink.

2 Responses

  1. Another great write Allen. I wonder how the statistics varied when men with life expectancies of less than 15 years at the time of treatment are removed from the data. I believe it may make overall survival significant.

  2. Thanks, Tony. For the benefit of our readers, let me explain that it’s often hard to ascertain from death records whether prostate cancer was the actual cause of death, so we look at both cause-specific survival and overall survival, and it does help too to consider actuarial life expectancy based on age and comorbidities. In this case, I think RTOG was pretty scrupulous in ascribing cause of death. As you can see, the “cause-specific survival” was significantly improved by the longer course of ADT.

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