When can ADT be safely avoided with salvage radiation therapy?

Two randomized clinical trials (GETUG-AFU-16 and RTOG 9601) proved that adding at least some ADT to salvage radiation (SRT) improved outcomes. “Some ADT” was 6 months of goserelin acetate in the GETUG-AFU-16 trial, and 2 years of bicalutamide in the RTOG 9601 trial. Retrospective studies have suggested improved outcomes as well (see this link and this one). On the whole, adjuvant ADT improves SRT outcomes. But is there a subgroup of patients, especially those treated early enough, in whom adjuvant ADT can be safely avoided?

This was the subject of a retrospective analysis by Gandaglia et al. They examined the records of 525 post-prostatectomy patients treated with SRT at six international institutions between 1996 and 2009. Inclusion criteria were:

  • Undetectable PSA (<0.1 ng/ml) after prostatectomy
  • Biochemical recurrence — two consecutive PSA rises above 0.1 ng/ml
  • PSA mostly ranged from 0.2 to 0.9 ng/ml (median 0.4) at the time of SRT
  • No detected lymph node metastases

There were 178 patients who received adjuvant ADT (median 15 months) and 347 who had SRT without ADT. Compared to those who received no ADT, those that did:

  • Were similar in age, initial (pre-op) PSA, and Gleason score
  • Were more likely to be stage T3b/4
  • Were less likely to have positive margins
  • Received higher SRT dose (70 Gy vs 66 Gy)

There was a median follow-up of 8 years for those who had no ADT, and 12 years for those who had adjuvant ADT. The authors compared the actual 10-year metastasis rate to the predicted 10-year metastasis rate based on PSA at SRT, Gleason score, stage, positive margins, SRT dose, and whether lymph nodes were treated.

They found that:

  • Only those with a 10-year probability of distant metastases greater than 1 in 3 benefited from the addition of ADT.
  • The benefit grew exponentially with increasing risk.
  • Adjuvant ADT only benefited those with higher PSA (≥ 0.4 ng/ml), Gleason scores of 8 to 10, stage T3b/4.
  • Higher SRT dose and whole pelvic SRT improved outcomes independently of whether adjuvant ADT was used.

It should be noted that high-dose SRT and whole pelvic treatment were used in a minority of cases, and there is a significant risk of selection bias in this study.

The authors conclude that a higher radiation dose alone may be sufficient to treat many patients with a recurrence detected early enough, but for those with aggressive tumor characteristics, adjuvant ADT will improve outcomes measurably. While this was not proved with a randomized trial, it does suggest that adjuvant ADT will not be necessary in all cases of SRT. Patients who are undecided may wish to have a Decipher genomic classifier done on their prostate tissue to determine their 10-year risk of metastases.

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

One Response

  1. After surgery March, 2012, Gleason 7, 4/3, tumor on one side of prostate, no lymph nodes, no margins, PSA = 0.3. Year later, PSA = 0.6. Salvage radiation June 2013. No ADT because, I theorized, if PSA went down, we wouldn’t know why. PSA checked every 6 months since radiation. Has been going down steadily each 6-month visit to doctor. Today, PSA = 0.039. Today, 66 years old.

    I’m guessing a few buggers jumped the fence which means wouldn’t have got them anyway. ut I’ve enjoyed a libido, and a sex life, for the last 5 years and, if ever forced to go to hormones, have postponed castration resistance. For now, have 5 months of sex and pleasure, and 1 month anxiety before next PSA test.

    Probably the best I could reasonably hope for. Everyone’s got to read, study, calculate the odds … and roll the dice. Good luck to all.

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