18 months of ADT as good as 3 years when combined with radiation


For many years the “standard” time on treatment with androgen deprivation therapy (ADT) in combination with radiation therapy for men diagnosed with high-risk prostate cancer was 3 years, based on data from Bolla and his colleagues in Europe. This length of time on ADT has often been questioned, and a new standard may just have been set.

At the annual Genitourinary Cancer Symposium, which starts tomorrow in Orlando, Nabid et al. will present data from a randomized, Canadian trial suggesting that 18 months of adjuvant ADT may be long enough to optimize the chance of curative therapy with radiation and ADT for such patients.

In this trial (the so-called PCS IV study), Nabid et al. randomized patients with high-risk, node-negative prostate cancer (clinical stage T3-4N0, PSA > 20 ng/ml or Gleason score > 7) to pelvic radiation therapy and either 36 months  (Arm 1) or 18 months (Arm 2) of ADT. The primary endpoint of the trial was overall survival.

Radiation was given to the prostate (70 Gy over 7 weeks) and to the whole pelvis (44 Gy over 4.5 weeks). Androgen deprivation was initiated with bicalutamide (50 mg for 1 month) and then goserelin acetate (10.8 mg every 3 months for either 18 or 36 months). The androgen deprivation was initiated prior to radiation therapy.

Here are the key findings of the study, as discussed at a press conference yesterday:

  • The trial enrolled 630 patients between October 2000 and January 2008.
    • 310 patients were randomized to Arm 1.
    • 320patients were randomized to Arm 2.
  • Patients’ characteristics were well balanced between the two arms.
    • Average (median) patient age was 71 years.
    • Median patient PSA level was 16 ng/ml.
    • Median Gleason score was 8.
    • Most patients had clinical stage T2N0 or T3N0 disease.
  • At a median follow-up of 77 months,
    • 71/310 patients (22.9 percent) in Arm 1 had died.
    • 76/320 patients (23.8 percent) in Arm 2 had died.
    • This difference was not statistically significant (p = 0.802).
    • 116 of the 147 patients who had died did so from causes other than prostate cancer.
  • The 5-year overall survival rates were
    • 92.1 percent for men in Arm 1
    • 86.8 percent for men in Arm 2
  • The 5-year prostate cancer-specific survival rates were
    • 97.6 percent for men in Arm 1
    • 96.4 percent for men in Arm 2
  • The 10-year overall survival rates were
    • 63.6 percent for men in Arm 1
    • 63.2 percent for men in Arm 2
  • The 10-year prostate cancer-specific survival rates were
    • 87.2 percent for men in Arm 1
    • 87.2 percent for men in Arm 2
  • There were no significant differences in the rates of biochemical, regional, or distant failure between Arm 1 and Arm 2.
  • Only patient age at the time of enrollment significantly impacted risk for death on multivariate analysis.

Nabir et al. conclude that their study “shows that long term [ADT] can be safely reduced from 36 to 18 months without compromising outcomes” of combination therapy using radiation and ADT in men with high-risk, localized prostate cancer.

Additional information about this study is available in a commentary on the MedPage Today web site. The moderator of the media briefing, Dr. Bruce Roth of Washington University in St. Louis, Missouri, clearly indicated that he believed that this study was practice changing, and was quoted as follows:

If anything, over the last couple of years, the information we have gotten about the long-term consequences of androgen deprivation is more striking than the positive aspects of prolonging therapy. I think probably the most important thing is the chance of getting testosterone back at end of therapy.

Certainly a shorter course of ADT will increase the potential for good recovery of serum testosterone levels once the course of ADT is completed.

3 Responses

  1. Dear Sitemaster:

    For me it’s unclear. What is the starting point for the mentioned 18 orer 36 months?

    You wrote:”Androgen deprivation was initiated with bicalutamide (50 mg for 1 month) and then goserelin acetate (10.8 mg every 3 months for either 18 or 36 months). The androgen deprivation was initiated prior to radiation therapy.”

    What means this for the total duration of the ADT, 1 month of adjuvant bicalutamide, 1 month of goserlin acetate concomitant with RT and then 18 months or 36 months of ADT? Means at the bottom line to months longer than 18 oder 36 months.

    In your link to MedPage Today I can read: “Randomized therapy began 4 months before definitive radiation therapy, continued during radiation therapy and for the specified duration of the treatment group.”

    Does this mean a total duration of 4 months of adjuvant ADT, concomitant ADT with RT for 1 months, and than 18 or 36 months ADT. That means 5 months longer ADT than in the reports mentioned?

    What is right?

  2. Gunterman:

    Based on the various reports available I am pretty sure that the trial required a total of 18 months or 36 months of ADT — from the start of bicalutamide therepy before radiation treatment to the end of ADT. However, it is possible that it might have required 1 month of bicalutamide prior to initiation of LHRH agonist therapy and then a total of 18 or 36 months of LHRH agonist therapy (i.e., 19 or 37 months of therapy in total).

  3. Thank you very much for your fast answer.

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