Radiation Therapy for High Risk Prostate Cancer: Do Patients 70 Years or Older Benefit from Combined Androgen Deprivation Therapy?

Reviewer: Arpi Thukral, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: September 25, 2008

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Presenter: J. S. Silverman, MD
Presenter's Affiliation: Fox Chase Cancer Center, Philadelphia, PA
Type of Session: Scientific

Background

  • It has been well established from previous research that long-term (2 to 3 years) of androgen deprivation therapy (ADT) significantly improves survival in men with high-risk prostate cancer. ADT is now widely being used in combination with local therapies such as radiation therapy. 
  • However, recent research has also demonstrated that ADT can lead to and increased risk of cardiovascular disease in some men by increasing the risk of metabolic syndrome in these patients.
  • The concern for cardiovascular disease in elderly patients undergoing long-term ADT may lead physicians to not offer hormone treatment to their patients on the basis of age.
  • The objective of this retrospective analysis was to determine whether age should be used to alter recommendations for ADT. 
    • Specifically, do the benefits of ADT in high risk prostate cancers over the age of 70 outweigh the risks of cardiovascular and metabolic adverse effects from androgen deprivation therapy?

Materials and Methods

  • This study is a retrospective analysis of 530 men with high risk prostate cancer who received radiation therapy at Fox Chase Cancer Center between 1988 and 2004. It was performed to evaluate differences between patients who were <70 years age vs. those >70 years old.
  • Patients had either T3/T4 tumors, a Gleason Score of 8-10, and/or PSA >20 ng/mL to be included in the study. 
  • All patients were treated with 3D conformal radiation therapy to a mean dose of 75.8 Gy. Whole pelvis was treated in 84% of patients. The median duration of ADT was 13 months (range: 1 - 92 months).  
  • The authors sought to determine relationships between radiation, ADT, age, biochemical failure (BF), distant metastasis (DM), and overall survival (OS). 
  • Overall survival analysis was performed using Kaplan-Meier estimates. 
  • Biochemical failure was defined as PSA nadir +2 ng/mL. 
  • The Fine-Gray method was used to calculate cumulative incidences for BF and DM.  
  • Patient self-reporting was used for assessment of cardiac morbidity. CAD, MI, CABG, and stenting were included as criteria for definition of cardiovascular disease.  
 

Results

  • Patient characteristics were well balanced between the 2 groups of those <70 vs. >70 years old with regards to initial PSA, Gleason score, clinical T-stage, and ADT duration. 
  • Mean age = 69 years (range: 45-89 yrs).   
  • Median PSA was 21 ng/ml (range: 2-146 ng/ml).  
  • Median follow up from completion of RT was 85 months (26-206 months).  
  • In terms of rates of cardiovascular (CV) disease, the older patient group had a significantly higher rate of CV disease: 34% vs. 24%, p=0.01.  
  • When comparing those patients who received ADT to those who did not, there was a clear advantage see for freedom from biochemical failure, OS, and DM with p<0.01 for the ADT group at 5 years. 
  • BF was significantly lower at 5 years for <70 year old patients receiving ADT compared to those who did not: 21% vs. 47%, p<0.0001.  In > 70 year old patients, this advantage was also seen for those receiving ADT: 15% vs. 32%, p=0.02.
  • OS was also significantly different in patients <70 who received ADT vs. those who did not: 96% vs. 91%, p=0.03.  However, this same OS difference was not seen for the older group (>70): 89% vs. 86%; p=0.17
  • Patients who received longer term ADT (>12 months vs. <12 months) had higher rates of 5-year OS in all men, regardless of age: 87% vs. 98%, p=0.02.  

Author's Conclusions

  • In high-risk prostate cancer patients >70 years old, ADT in combination with radiation therapy does improve BF rates.
  • However, this did not translate to an OS advantage for this older patient population. This may be explained in part by greater pre-existing cardiovascular conditions in men over age 70.  
  • In addition, longer duration of ADT (>12 months) was associated with an increase in OS for both age groups. 
  • Age alone should not be considered a contraindication to hormone treatment in high-risk patients.
  • These data do not provide enough information to help define or select patients for which recommendations for ADT should be altered on the basis of age.  

Clinical/Scientific Implications

  • Although previous work has demonstrated that ADT provides a significant OS benefit in high-risk prostate patients, older patients are often not offered ADT due to its competing cardiovascular risks. There is a currently a paucity of studies examining this topic. 
  • The authors of this study make a valiant attempt to determine if one can select patients based on age in which the cardiovascular risks of ADT may outweigh its potential benefits.   They have shown that ADT does improve BF rates in older patients, but this did not translate into an OS difference.  
  • However, this study does not provide enough data to select patients who should or should not receive treatment of a shorter duration based on age alone. 
  • As pointed out by the authors themselves, a major weakness of this study is selection bias because it is a retrospective analysis, and therefore patients were not randomized to androgen deprivation therapy.
  • It would also be valuable to examine the causes of death in the older patient population to see if an increase in CV related deaths accounted for the fact that no difference in OS was seen in these patients.
  • As physicians, we need to continue to tailor decisions on ADT for older patients based on considerations involving individual patients themselves. Additionally, it is important to remember that many patients themselves do not want to undergo ADT, because it negatively impacts their QOL. For this reason, we need to continue work in the area of patient selection for ADT.  
  • Although this study had the limitations of a retrospective analysis, this data adds to the current literature on patient selection for ADT.  
  • Future studies need to be done with larger cohorts to answer the questions outline above. In addition, prospective work should also examine associations with factors like weight, BMI, and other CV risk factors.