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

Background

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

Results

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.