Addition of Radiation Therapy to Androgen-Deprivation Therapy Also Benefits Elderly Patients with Locally Advanced Prostate Cancer

SUMMARY: Prostate cancer is the most common cancer in American men with the exclusion of skin cancer and 1 in 7 men will be diagnosed with prostate cancer during their lifetime. It is estimated that in the United States, about 220,800 new cases of prostate cancer will be diagnosed in 2015 and over 27,000 men will die of the disease. The development and progression of prostate cancer is driven by Androgens. Androgen Deprivation Therapy (ADT) has therefore been the cornerstone of treatment of advanced prostate cancer and is the first treatment intervention for hormone sensitive prostate cancer. Prostate cancer in general is a disease of the elderly and is a leading cause of cancer mortality in men, second only to lung cancer. Elderly patients however are often under-represented in clinical trials. This is in spite of data published in previous studies showing that an average 75 yr old male in the United States has an additional life expectancy of 11 years. Further in clinical practice, elderly patients are less likely to receive either Surgery or Radiation Therapy (RT) and this is also true in men with high risk prostate cancer. This mind set has been further reinforced by recent recommendations against PSA screening and role of close surveillance for patients with low risk prostate cancer.

It is generally perceived that clinically localized prostate cancer is an indolent tumor. Patients with clinically localized prostate cancer can present with either locally advanced prostate cancer or prostate cancer detected by PSA screening. Patients with locally advanced disease have clinical stage T3 disease with tumor extending beyond the confines of the prostate gland. The 10 yr mortality in this patient group is as high as 25%. Patients with PSA screening-detected prostate cancer may have earlier stage disease with a much better prognosis. However, in this subgroup, those with poorly differentiated or undifferentiated clinical stage T1c tumors, with a Gleason score of 8-10, have a significantly higher mortality rate. It is now well established that the addition of Radiation Therapy (RT) to Androgen Deprivation Therapy (ADT) improves Overall Survival compared to ADT alone, in patients with locally advanced prostate cancer. However, these studies did not include patients over 75 years of age or those with PSA screen detected high risk prostate cancer.

With this age-biased background, the authors conducted a non-randomized observational study to assess, whether the survival advantage of ADT plus RT over ADT alone, reported in clinical trials, could be replicated in real world clinical practice, to two subgroups of patients poorly represented in the clinical trials such as, men older than 75 years, with locally advanced prostate cancer and men age 65 years or older, with PSA screen detected high risk prostate cancer. Utilizing the SEER-Medicare data set, the authors reviewed the effectiveness of ADT plus RT compared to ADT alone in three groups of patients diagnosed with localized prostate cancer between 1995 and 2007 and observed through 2009. These three groups included 1) The Randomized Clinical Trial (RCT) cohort, which included men age 65 to 75 years, a profile consistent with participants in the randomized trials 2) The elderly cohort, which included men over 75 years of age, with locally advanced prostate cancer 3) PSA screen-detected cohort, which included men 65 years or older with PSA screen-detected high risk prostate cancer. The cause-specific and all-cause mortality was determined in these patient groups.

It was noted that in the RCT cohort, ADT plus RT was associated with reduced cause-specific and all-cause mortality compared to ADT alone and these finding were not significantly different from published randomized trials data. Interestingly, similar Overall Survival benefit was noted in the elderly and PSA screen-detected cohorts, with ADT plus RT. The authors in this thought provoking study concluded that older men with locally advanced or PSA screen-detected high-risk prostate cancer should also be offered ADT plus Radiation Therapy, as this therapeutic modality can improve Overall Survival. Effectiveness of Androgen-Deprivation Therapy and Radiotherapy for Older Men with Locally Advanced Prostate Cancer. Bekelman JE, Mitra N, Handorf EA, et al. J Clin Oncol 2015;33:716-722