Hormone therapy with and without radiotherapy in high-risk, localized prostate cancer

In September this year, writing from the 50th annual meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO), Dr. Eyad Abu-Isa addressed breaking news of a Scandinavian trial comparing radiotherapy + hormone therapy to radiotherapy alone in the treatment of locally advanced prostate cancer. The complete results of this study in were just published in The Lancet .

In this paper, Widmark et al. describe their randomized clinical trial included 875 patients recruited at 47 different centers from three Scandinavian countries (Norway, Sweden, and Denmark) between 1996 and 2002. The majority of the patients (78 percent) were diagnosed with clinical stage T3N0M0 disease and had PSA levels of < 70 ng/ml.

Just over half the patients (439/875) received hormone therapy alone (3 months of combined hormone therapy with an LHRH agonist + flutamide, followed by continuous hormone therapy with flutamide). The other half (436/875) received the same hormonal management together with the addition of external beam radiotherapy.

The results of the trial can be summarized as follows:

  • After a median follow-up of 7.6 years, 79 of the men in the hormone-only group and 37 of the men in the hormone + radiotherapy group had died of prostate cancer.
  • The cumulative incidence of prostate cancer-specific mortality at 10 years was 23.9 percent in the hormone therapy group and 11.9 percent in the hormone therapy + radiotherapy group.
  • Also at 10 years, the cumulative incidence of overall mortality was 39.4 percent in the hormone therapy group and 29.6 percent on the hormone therapy + radiotherapy group.
  • And finally the cumulative incidence at 10 years for PSA recurrence was 74.5 percent in the hormone therapy group compared to only 25.9 percent in the hormone therapy + radiotherapy group.
  • With respect to adverse events, it does need to be noted that (at 5 years of follow-up) patients in the hormone therapy + radiotherapy group had a slightly greater frequency of occurrence of urinary, rectal, and sexual problems than those who received hormone therapy alone.

As we pointed out when these data were initially reported from ASTRO, this is a critically important trial because it is the first time that it has been shown that the combination of hormone therapy + radiation therapy extends the survival of high-risk prostate cancer patients compared to hormone therapy alone. Earlier studies (in the USA and Europe) had shown that hormone therapy + radiation therapy was superior to radiation therapy alone. Now we have clarified that the combination is also better than its other single component.

Does the survival benefit outweigh the side effects? The answer to that would seem to be yes, at least for any patient who can expect a significant survival potential. Quoted in USA Today , Dr. Howard Sandler, a member of the Scientific Advisory Board of The “New” Prostate Cancer InfoLink who was not involved in this study, stated, “The magnitude of the benefit is remarkable.”

On the other hand, the form of hormone therapy used in this trial is unusual, with only 3 months of hormone therapy followed by long-term antiandrogen monotherapy. A comparable US-based trial would have been more likely to use short-term combination therapy with an LHRH agonist and an antiandrogen followed by long-term LHRH agonist therapy alone. We don’t know if this might have modified the trial results. Nor do we know if the concept of 3 months of combination therapy followed by continuous monotherapy offers an improved survival benefit over a shorter hormonal regimen when combined with radiotherapy.

Another question that may arise in the very near future will be whether a hormonal regimen comprising 3 months of degarelix followed by 3 years of bicalutamide combined with external beam radiation might offer the same survival benefit with even fewer adverse events over time.

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