No 15-year survival benefit associated with primary ADT in older men

In another paper just published on-line in JAMA Internal Medicine this week, the authors have provided additional data indicating — once again — the lack of any value of primary androgen deprivation therapy (ADT) in the management of early-stage, localized prostate cancer among older patients.

Lu-Yao et al. report on an analysis of data from a cohort of > 66,000 Medicare patients diagnosed between 1992 and 2009, all of whom received no form of definitive therapy (such as surgery or radiation therapy) in the first 180 days after their diagnosis. All these patients were 66 years of age or older, and the study was carried out based on predefined geographic regions of the USA covered by the Surveillance, Epidemiology, and End Results (SEER) program.

Here are the basic findings of this study:

  • The average (median) follow-up of patients in this study was 110 months or just over 9 years.
  • Compared to delayed use of ADT (to manage actual symptoms or prevent imminent symptoms of advanced prostate cancer)
    • Primary ADT had no evident, 15-year overall or prostate cancer–specific survival benefit when used as a first-line treatment following the diagnosis of localized prostate cancer.
  • Among men with moderately differentiated cancers,
    • The 15-year overall survival was 20.0 percent in areas with high use of primary ADT.
    • The 15-year overall survival  was 20.8 percent in areas with low use of primary ADT.
    • The 15-year prostate cancer-specific survival was 90.6 percent in the high- and the low-use areas.
  • Among patients with poorly differentiated cancers,
    • The 15-year overall survival was 8.6 percent in areas with high use of primary ADT.
    • The 15-year overall survival was 9.2 percent in areas with low use of primary ADT.
    • The 15-year prostate cancer-specific survival was 78.6 percent in high-use areas.
    • The 15-year prostate cancer-specific survival was 78.5 percent in low-use areas.

It is very apparent from these data that early use of primary ADT alone in this cohort of men > 66 years of age made no significant difference whatsoever to their overall or their long-term prostate cancer-specific survival.

Lu-Yao and her colleagues conclude that:

Primary ADT is not associated with improved long-term overall or disease-specific survival for men with localized prostate cancer. Primary ADT should be used only to palliate symptoms of disease or prevent imminent symptoms associated with disease progression.

The “New” Prostate Cancer InfoLink wishes to be extremely clear about the relevance of this study. It only applies to men of 66 years and older who are diagnosed with clinical stage T1 and T2 prostate cancer who are either not appropriate for some other form of primary therapy or who refuse to have such therapy. It does not necessarily apply to younger men or to a man of 66 years of age (or older) with intermediate- or high-risk prostate cancer who has a life expectancy of 10 or more years and who may be an appropriate candidate for definitive and potentially curative therapy (such as radical surgery or radical surgery + adjuvant radiation therapy or radiation therapy + ADT).

What primary ADT does do for older patients with clinical stage T1 and T2 disease is that it may manage their anxiety by dropping their PSA levels into the “undetectable” range, but in doing this it also — commonly — comes with a range of complex side effects, potentially including loss of erectile function and sexual desire, hot flashes, weight gain, gynecomastia, and, in some cases, effects on mental processes such as memory, attention, and the ability to concentrate and focus. Early use of ADT may also accelerate the potential onset of castration-resistant disease in some patients.

While The “New” Prostate Cancer InfoLink understands the attraction of managing anxiety, we believe it is extremely important for patients to understand that this benefit is offset by the potential downsides of treatment, and that there is no strong evidence for a survival benefit of any type.

Are there some men who may benefit from the early use of ADT? Yes, there are. These are likely to be men with a rapidly rising PSA level (i.e., a short PSA doubling time) who are not good candidates for any form of definitive therapy. However, many other older men who are not good candidates for definitive therapy are likely to do much better (in terms of quality of life) if they delay initial use of ADT for as long as they can reasonably manage — i.e., until there are evident symptoms associated with their prostate cancer or evidence of metastasis or progressive disease on a bone scan or some other type of scan.

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