Is Androgen Deprivation Therapy Necessary in Intermediate Risk Prostate Cancer Patients Treated in the Dose escalation Era?
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 4, 2011
Presenter: K.O. Castle Presenter Affiliation: MD Anderson Cancer Center, Houston, TX
Studies have shown androgen deprivation therapy (ADT) to increase over all survival (OS) in intermediate and high risk prostate cancer patients (D'amico, JAMA 2004). However, most of the prospective data supporting use of ADT comes from studies that looked at patients treated with lower doses of RT than are used currently.
Role of ADT is controversial in the era of dose escalation especially in light of retrospective data suggesting increased risk of cardiovascular disease in patients on ADT.
Goal of this study was to identify patients more likely to benefit from ADT in the dose escalation era and to compare patients with and without ADT in regards to biochemical disease free survival (bDFS).
Men with intermediate risk prostate cancer treated at MD Anderson Cancer Center between 1993-2008 with doses ranging between 75.6-78 Gy were retrospectively identified:
327 patients received radiation alone
218 patients received radiation and less than/equal to 6 months of hormones
For comparison group, 274 low-risk patients treated with definitive radiation were also identified.
Using bDFS as outcome, Gleason Score (GS), pre-treatment PSA and T stage were used for recursive partitioning analysis (RPA) to divide all intermediate risk patients into favorable, marginal and unfavorable groups.
Patients with intermediate risk disease who received radiation alone were compared to patients with radiation and ADT and low risk patients.
Kaplan Meir curves were generated to evaluate bDFS in intermediate (with RT and RT/ADT) and low risk groups.
For the intermediate risk group, RPA of dDFS at 5 years was used to define:
Favorable patients-T1b-T2b GS 6 or Tb-c GS 3+4 (n=188)
Marginal patients-T2a-b GS 3+4 (n=71)
Unfavorable patients-T2c or GS 4+3 (n=68)
Hazard Ratio (HR) of 1.0 for favorable group as baseline, HR of marginal patients was 2.1, and unfavorable patients was 4.5.
Patients who received radiation alone: Median follow up was 5.7 years. Five year bDFS was 94% in the favorable group, 91% in marginal group and 74% in unfavorable group.
Patients who received radiation and ADT: Median follow up was 4 years. Five year bDFS was 95% in favorable group, 100% in marginal group and 94% in unfavorable group.
In regards to patient characteristics, age PSA and RT dose was balanced. RT+ADT group had higher number of patients with Gleason 7 disease.
When comparing, RT vs RT+ADT groups in regards to 5 year bDFS, patients with unfavorable disease got the most benefit from ADT (bDFS 74% in RT group vs 94% in RT+ADT group, HR 0.234 p=0.005). In marginal group, difference in 5 year bDFS didn't reach significance (bDFS 95% in RT group vs 100% in RT+ADT group, p=0.07). In favorable group, 5 years bDFS was comparable in the RT vs RT+ADT groups (bDFS 94% in RT group vs 95% in RT+ADT group, p=0.85).
Patients in low risk group and favorable intermediate group with RT alone had similar bDFS at 5 years (98% for low risk with RT alone vs 94% for favorable intermediate group with RT alone).
No statistical difference in regards to cause specific survival with follow up of 58 months was noted.
There is no benefit of ADT in addition to high dose RT in favorable risk group patients.
Patient will unfavorable disease, GS 4+3 and higher T stage, benefit from addition of ADT to high dose RT.
Further results of randomized trial (RTOG 0815 and 0924) will help stratify patients in dose escalation era that will achieve most benefit from addition of ADT.
Clinical and Scientific Implications
Since randomized data is lacking in this area, this study raises a very important point: not all intermediate risk patients are the same and we should select patient keeping in mind their various risk factors and other co-morbidities in designing an appropriate and individualized treatment plan.
Further randomized data in this area will be very helpful in creating guidelines for role of ADT in intermediate risk prostate cancer patients.