Survival Benefit for Early Initiation of Hormone Ablation Therapy in Patients who Fail Definitive XRT for Prostate Cancer (ACP)

Ryan Smith, MD
University of Pennsylvania Cancer Center
Last Modified: November 4, 2001

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Presenter: T.C. Tenenholz
Affiliation: Medical College of Virginia

Background
There is a dispute over the timing of starting hormones after biochemical failure. This study was initiated to determine when the benefits of hormonal ablation outweighs its potential morbidity.

Materials and Methods

  • Retrospective study of 931 patients who recieved XRT (635 with curative intent)
  • 394 patients were controlled by XRT, with 241 having biochemical failure (PSA > 1mg/dl). All biochemical failures had metastatic workup upon diagnosis of failure.
  • Hormonal initiation was done at the discretion of the clinician with no formal policy.
  • Primary endpoints were OS, DSS, Duration of hormonal control

Results

  • Hormones had statistically significant improvement in OS and DSS if PSA at time of initiation was <15 ng/ml or PSA doubling time (DT) was > 7 months (OS=70.8%, DSS=86.4% at 5 years).
  • No additional benefit was seen if hormones were initiated with PSA <10 ng/dl or DT >12 mo.
  • OS, DSS was much better in patients who were started on hormones with PSA < 15 ng/dl and DT >7 months
  • DT and PSA were best predictors of OS and DSS

Author's Conclusions

  • These data support the concept that patients will benefit more from hormonal ablation before the development of metastatic disease or a heavy tumor burden.
  • Patients with biochemical failure and a high PSA or short DT have a poor outcome, similar to metastatic disease
  • This has led to an institutional policy of initiating horomes when a patient's PSA level is >10 ng/ml or has a PSA doubling time of < 1 year

Clinical/Scientific Implications
The timing in the initiation of hormones after biochemical failure is a topic of debate in the radiation oncology literature. Many have advocated early initiation with claims that it extends the DFS and symptomatic free survival. These data presented seem to support this conclusion. This has led to guidelines of initiating hormonal ablation prior to the development of metastatic disease or heavy tumore burden as evidenced by large PSA. From this study, it seems as though the longer time until hormones are initiated, the worse patients do, both in terms of overall survival and disease free survival. However, how it affects the actual history of disease is not known. This needs to be investigated in a prospective study.