Duration of androgen deprivation therapy in high-risk prostate cancer: A randomized trial
Reporter: Jacob Shabason, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 10, 2013
Presenter: Abdenour Nabid, MD Presenter's Affiliation: Centre Hospitalier Universitaire de Québec, Québec, QC, Canada Abstract #: LBA4510
Radiotherapy and long-term androgen deprivation therapy (ADT) is a standard treatment for patients with high-risk prostate cancer.
Prior trials have shown improvements in overall survival in high-risk patients treated with 36 months of ADT compared to both no ADT (EORTC 22863) and 6 moths of ADT (EORTC 22961).
However, the optimal duration of ADT is not yet completely defined.
ADT had significant toxicity including sexual, musculoskeletal, metabolic and cardiovascular toxicity.
The authors performed a phase III, randomized trial comparing the outcomes of 36 vs.18 months of ADT with radiotherapy in patients with high- risk prostate cancer.
Materials and Methods
The trial included high-risk (T3-4, PSA >20 ng/ml or Gleason score >7), node negative and non-metastatic prostate cancer patients.
All patients received pelvic radiation (whole pelvis 44 Gy/4 ½ weeks, prostate 70 Gy/7 weeks) and were randomized to 36 (arm 1) vs.18 months (arm 2) of ADT (neo- adjuvant, concomitant, adjuvant).
ADT consisted of bicalutamide 50 mg for one month and goserelin 10.8 mg every three months for 36 vs. 18 months.
The primary endpoints were overall survival (OS), disease specific survival (DSS) and quality of life (QOL).
OS and DSS rates were compared between arms with Kaplan-Meier log rank test and Cox regression.
Secondary endpoints included disease free survival (DFS), biochemical failure (BCF) and site of first relapse.
Materials and Methods
From October 2000 to January 2008, 310 patients were randomized to 36 months of ADT and 320 to 18 months of ADT.
Patients' characteristics were well balanced between the two arms (median age 71 years, median PSA 16 ng/ml, median Gleason score 8 and most patients had T2-T3 disease).
At a median follow-up of 78 months, 80/310 patients (25.8%) in arm 1 and 85/320 (26.6%) in arm 2 had died (p=0.829).
113 patients died of causes other than prostate cancer.
Overall and cancer-specific survival hazard ratios were 1.15 (0.85-1.56), p=0.366 and 1.07 (0.62-1.84), p=0.819, respectively.
Five year OS was 91.1% (87.9-94.3) vs. 86.1% (82.3-90.0), p=0.06 and 5 year DSS was 96.6% (94.5-98.7) vs. 95.3% (92.8-97.7), p=0.427.
Ten year OS was 61.9% (54.1-69.7) vs. 58.6% (49.8-67.4), p=0.275 and 10 year DSS was 84.1% (77.6-90.6) vs. 83.7% (76.3-91.1), p=0.819.
There were also no significant differences in rates of biochemical, regional or distant failures between the two arms.
With a median follow up of 78 months this randomized study indicates that long-term ADT can be safely reduced from 36 to 18 months without compromising any outcomes in patients with high-risk prostate cancer.
This decrease will presumably decrease toxicity related to ADT and improve QOL, however the analysis on quality of life is still pending analysis.
A standard treatment approach of patients with high-risk prostate cancer is radiotherapy with 2-3 years of neoadjuvant, concomitant and adjuvant ADT.
Due to the fact that ADT has significant morbidity, there is much interest in attempting to decrease the duration of this therapy.
This trial indicates that the duration of ADT can safely be decreased from 36 to 18 months with similar outcomes.
This shortened therapy would presumably be better tolerated, however toxicity data from the trial is still pending.
In addition, this trial was started before the benefit of dose-escalated radiotherapy (of greater then 78 Gy) was established in prostate cancer and all patients were treated to 70 Gy.
With dose escalated radiotherapy the duration of ADT could potentially be safely shortened to less then 18 months and further research could be designed to address this question.
Jun 22, 2011 - Men who are smokers at the time of prostate cancer diagnosis have an increased risk of total mortality, cardiovascular disease mortality, prostate cancer mortality, and recurrence, according to a study published in the June 22/29 issue of the Journal of the American Medical Association.