The management of high- and intermediate-risk prostate cancer in elderly males


Overall life expectancy of men in the US continues to rise. As a consequence, the way we treated localized prostate cancer in men of ≥ 70 years of age in 1990 will probably not be relevant or appropriate to the way we need to treat such men in 2020 (or perhaps even today). Let’s begin with some facts.

  • In the year 2000, about 12 percent of American males were > 65 years of age (see Crawford et al.).
  • In the year 2030, about 20 percent of American males will be > 65 years of age (see Crawford et al.).
  • The average life expectancy of a 70-year-old American male in 2000 was another 13 years (see Minino and Smith).
  • 64 percent of new prostate cancer cases in the US are being diagnosed in men > 65 years of age (see Heinzer and Steuber).
  • 23 percent of new prostate cancer cases in the US are being diagnosed in men > 75 years of age (see Heinzer and Steuber).

In other words, by 2020 there will be a lot more men of 70 years of age or more who are getting diagnosed with localized prostate cancer and have a reasonable life expectancy of 15+ years.

It is in this context that we need to appreciate the data from the recent study by Bechis et al. entitled “Impact of age at diagnosis on prostate cancer treatment and survival.” We mentioned this article briefly in an earlier post, but we have now had the opportunity to review the text of the entire article.

Bechis et al. have compiled data on the treatment and outcomes of men aged 70 years or more who were diagnosed with localized prostate cancer based on the information in the CaPSURE database. They then compared the treatment and outcomes of these men to other patients in the same database whose sole differentiating characteristic was that they were less than 70 years of age. To be eligible for inclusion in the analysis, the patients all had to have localized disease, each patient’s type of primary treatment had to be known, and there had to be at least 6 months of follow-up data available. Patient risk at the time of initial diagnosis was based on the CAPRA score, which meant that high-risk patients were those with a CAPRA score of 6 to 10. It is important to understand that  the CaPSURE initiative was started in 1995 and so data in the current analysis is based on patients diagnosed and treated as early as 1995 through July 2008 — a 13-year timespan.

What have Bechis and his colleagues been able to demonstrate? Key findings from this study are summarized below:

  • The total number of patients eligible for this analysis was 11,790.
  • The number of patients aged between 66 and 75 years of age at diagnosis was 4,667 or 39.6 percent.
  • The number of patients aged >75 years at diagnosis was 1,707 or 14.5 percent.
  • The likelihood of diagnosis with high-risk disease (a CAPRA score of 6 to 10) increased significantly with increasing age
    • In men aged between 65 and 69 years it was 12.3 percent.
    • In men aged between 70 and 74 years it was 14.2 percent.
    • In men aged between 75 and 79 percent it was 21.4 percent.
    • In men aged 80 or more years it was 33.4 percent.
  • Older men with high-risk disease were far more likely to receive androgen deprivation (ADT) as their primary therapy than younger men at the same risk level
    • In high-risk men aged between 66 and 75 years the probability of primary ADT was 26 percent.
    • In high-risk men aged 76 years and older the probability of primary ADT was 60 percent.
  • Among 629 men ≥ 70 years of age with high-risk disease, 275 (44 percent) died during follow-up at a median of 5.7 years and 57/692 (8.2 percent) died of prostate cancer.
  • Among 392 men ≥ 75 years of age with high-risk disease, 183 (47 percent) died during follow-up at a median of 5.3 years and 36/392 (9.2 percent) died of prostate cancer.
  • Receipt of local therapy among older men with high-risk, localized disease was strongly associated with decreased mortality.
  • There were no survival differences between men receiving primary ADT and men receiving watchful waiting or active surveillance in any analysis.

Now it would be easy to conclude from this study that older men diagnosed with high-risk, localized prostate cancer should all be getting immediate localized treatment — but that would be a poor conclusion. Remember that this study is based on patients being diagnosed and initially treated as long ago as 1995. Many of those patients may have had high-risk disease because of the comparative newness of PSA testing. Also, at that time, there were really only four management options: surgery, external beam radiation, ADT, or watchful waiting. It is likely that under such a scenario the probability of management of older patients with watchful waiting or ADT was high.

A more appropriate conclusion that we can reach from these data is the importance of evaluating all patients based on physiological age, comorbidities, and life expectancy rather than on chronological age. As life expectancy continues to increase, this will only become more important. Intermediate- and high-risk patients of 70 and older need to be managed in ways that will optimize their overall survival and their quality of life, just like men of 50 or 55. Some of these patients will most certainly be candidates for immediate localized forms of therapy; others may not — because of their life expectancy and their comorbid conditions. But we need to avoid putting patients in treatment boxes based on chronological age alone. Any older patient with high-risk disease and a life expectancy of 10 or more years is a potentially good candidate for immediate localized therapy as opposed to primary ADT, but precise clinical decisions need careful discussion between that patient and his doctor(s).

2 Responses

  1. Thanks again for featuring this study and for your emphasis on the worth of primary definitive treatment for appropriate older men.

    There is reason to question one of the observations in the study: “There were no survival differences between men receiving primary ADT and men receiving watchful waiting or active surveillance in any analysis.” As a preliminary thought, I’m wondering whether survival was “prostate cancer specific survival,” “overall survival”, or both. Here are some other thoughts.

    First, based on the timeframe of the study, it’s highly likely that most of the men receiving hormonal therapy received monotherapy, most likely with an LHRH agonist or castration, rather than combined therapy with two drugs or triple therapy. Evidence is accumulating that two- and three-drug hormonal therapy is superior for many men.

    Second, based on patterns of medical practice that are still common today, it’s likely that for most of the men their hormonal therapy was not well managed with the aid of testosterone and DHT monitoring, both being practices that can significantly improve the effectiveness of ADT.

    Third, it’s likely that a substantial proportion of the men in the study who were diagnosed in the late 1990s had well advanced, metastatic disease at the outset; hormonal therapy is not as effective at that stage.

    Fourth, when you run the numbers to estimate the number of men who got hormonal therapy, the result is fairly small, indicating that statistical significance is probably questionable, especially if apples-to-apples risk group comparisons are made.

    Finally, it’s very important to keep in mind that, especially back when most of the men in the study would have been treated, hormonal therapy was typically reserved for men with the most challenging cases — cases deemed beyond the reach of other therapies. In sharp contrast, men on active surveillance are low- or very-low in risk; you would expect such men to have a marked superiority in survival to men with challenging cases as indicated by hormonal therapy. Men on watchful waiting may have been very low in risk or may have had other challenging health conditions that made watchful waiting reasonable.

    With all these considerations involved, I’m not sure what we can make of that finding of no difference between those men on hormonal therapy and those on watchful waiting or active surveillance.

  2. Dear Jim:

    I think you are over-analyzing these data. They are what they are, and the statement about “no survival differences” addresses prostate cancer-specific and overall survival. You should also please note (as stated above) that all the men in this study were initially diagnosed with localized disease.

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