A Randomized Trial Comparing Antiandrogens with or without Radiotherapy in the Treatment of Locally Advanced Prostate Cancer: Survival and QOL Outcome

Reviewer: Nathan Jones DO
Abramson Cancer Center of the University of Pennsylvania
Last Modified: September 23, 2008

Presenter: Anders Widmark
Presenter's Affiliation: Umeå University, Sweden
Type of Session: Scientific


  • Hormonal therapy has become a standard addition to definitive radiation therapy for higher risk and locally advanced prostate cancer.
  • Luteinizing hormone-releasing hormone (LHRH) antagonist administration, a form of medical castration that results in immediate androgen suppression, has supplanted surgical castration as the most common form of androgen deprivation therapy in the United States and Europe.
  • Anti-androgen therapy has been demonstrated to have a similar efficacy, yet fewer side effects, when compared to medical castration.

Materials and Methods

  • Multi-group prospective randomized study comparing lifelong hormonal therapy with or without the addition of radiation therapy for locally advanced prostate cancer
  • Inclusion criteria
    • T3 and Grade 1-3 or T1b-2 and Grade 2-3
    • N0
      • Presumed N0 if PSA ≤ 10 ng/dL
      • or if PSA is between 10 and 70 ng/dL, negative surgical lymph node sampling required 
    • No evidence of bony metastasis on bone scan
    • Age ≤ 75 years with life expectancy ≥ 10 years
  • Hormonal therapy consisted of 3 months of neoadjuvant total androgen blockade followed by lifelong anti-androgen therapy with Eulexin
  • Radiation therapy was 70 Gy to the prostate with 50-70 Gy to the seminal vesicles depending on suspicion of involvement
  • 3D conformal radiation fields were used with a 1.5-2 cm margin to the PTV
  • Rectal dose was limited to 70 Gy to ½ of the rectal volume
  • Quality of life was assessed by both physician evaluation and patient questionnaires
  • Primary endpoint was prostate cancer-specific survival, with secondary endpoints of biochemical progression free survival, local progression free survival, and quality of life


  • Multinational accrual across Scandinavia from 1996-2002
  • Baseline patient characteristics were well balanced between the two groups
    • ~ 78% of all patients had T3 disease
    • ~ 60% of all patients had PSA > 20 ng/dL
  • 880 patients with median age 67 years
  • Overall prostate cancer-specific mortality was improved with the addition of radiation therapy: 18% vs 8.5%
  • 10-year overall survival was improved in the radiation group: 23.9 vs 11.9% (p=0.00003)
  • PSA recurrence at 10 years was 74.7% vs 25.9%, with fewer recurrences in the group receiving radiation
  • When grouped by stage T1b-T2 vs T3, the benefits were similar
  • Patients with PSA > 20 ng/dL tended to have more benefit from radiation, but this did not reach statistical significance
  • Patient questionnaires regarding quality of life were completed with ~87% answer frequency
  • Patients receiving radiation reported experiencing more sexual bother and a small magnitude of increase in urinary bother and leakage

Author's Conclusions

  • Radiation therapy reduces prostate cancer-specific mortality from 18% to 8.5% in patients with locally advanced prostate cancer undergoing lifelong anti-androgen therapy.
  • This builds on the results of the SPCG-4 study, which demonstrated a 5% overall survival benefit in prostate cancer patients receiving prostatectomy vs. deferred treatment, but which consisted of a cohort with less aggressive baseline disease.

Clinical/Scientific Implications

  • These data support the current standard treatment for high risk and locally advanced prostate cancer with combined local radiation therapy and androgen deprivation therapy.
  • These data provide strong support for the role of local disease control in improving cancer-specific and overall survival. This is also supported by previous data from Coen in JCO ’02 and Zelefsky in J Urology ’08, which show improved distant metastasis-free and cancer-specific survivals when local control is achieved.
  • This study does not address the issue of dose escalation to the prostate, as it was initiated prior to the widespread use of radiation doses > 72 Gy.
  • The issues of optimal duration and types of hormonal therapy are not addressed, as both study arms used an identical, "lifelong" regimen.