Age-related diagnosis with M1 disease and age-related prostate cancer-specific mortality rates

According to a media release from the University of Rochester, a new study suggests that “men age 75 and older are diagnosed with late-stage and more aggressive prostate cancer and thus die from the disease more often than younger men.”

Frankly, we are having a really hard time with this media release, and with this interpretation of the data reported by Scosyrev et al. in Cancer.

What Scosyrev and his colleagues actually appear to have been able to show is the following: that between 1998 and 2007, the frequency of metastatic (M1) prostate cancer at time of diagnosis is higher in older men than in younger men!

There is no surprise here at all. If you don’t get diagnosed with prostate cancer until well into your 70s, it is inevitable that you have a higher likelihood of being diagnosed with metastatic disease. This merely reflects the fact that one can live a very long time with progressive prostate cancer before your symptoms suggest that there may be a clinical problem. What’s new?

Scosyrev et al. looked at the data from 464,918 patients diagnosed between 1998 and 2007 and accessible within the Surveillance, Epidemiology, and End Results (SEER) database. They sorted the patients into 5-year age groups at the time of diagnosis and then analyzed the available data for the occurrence of M1 disease and subsequent prostate cancer-specific mortality. Their findings were as follows:

  • The frequencies of M1 disease at the time of diagnosis were
    • 3 percent for men aged < 75 years
    • 5 percent for men aged 75 to 79 years
    • 8 percent for men aged 80 to 84 years
    • 13 percent for men aged 85 to 89 years
    • 17 percent for men aged ≥ 90 years
  •  The 5-year cumulative incidence of death from prostate cancer for all patients diagnosed with any stage of prostate cancer (not just those with M1 disease) was
    •  3 to 4 percent for men aged < 75 years
    • 7 percent for men aged 75 to 79 years
    • 13 percent for men aged 80 to 84 years
    • 20 percent for men aged 85 to 89 years
    • 30 percent for men aged ≥ 90 years.
  • Patients aged ≥ 75 years at diagnosis comprised
    • 26 percent of all prostate cancer cases
    • 48 percent of all cases of stage M1 disease
    • 53 percent of all cases of prostate cancer-specific mortality

The authors then draw the following series of conclusions:

  • Men of 75+ years of age were more likely to present with very advanced disease than men < 75 years of age.
  • Men of 75+ years of age had a greater risk of death from prostate cancer despite higher death rates from competing causes.
  • Men of 75+ years of age contributed more than half of all prostate cancer-specific deaths.

The “New” Prostate Cancer InfoLink understands that there are valid conclusions from this study. However, this does not in any way imply that older men are in some way more likely to get and die from aggressive prostate cancer. A much more valid interpretation of these data is that we are still really bad at diagnosing clinically significant prostate cancer at a time when it might still be treated effectively with curative intent — and there are several reasons for this, as follows:

  • Most men don’t do anything much to protect their long-term health.
  • Most men over 60 in 1998 had never had a PSA test and were therefore still at high risk for an initial diagnosis with symptomatic, metastatic disease
  • Many men diagnosed with progressive and incurable disease may get this diagnosis in their 50s and 60s, but it may still take 20+ years for this to progress to metastasis and death.

The median age at death from prostate cancer in the period 2003 to 200y7 was 83 years. The data from the current study are entirely compatible with these epidemiologic data. In the majority of men it takes a long time for prostate cancer to progress from diagnosis to death. Among men diagnosed today with symptomatic M1 disease, it may take as much as 7 to 10 years or longer for most men to die from metastatic, castration-resistant prostate cancer.

What is not available in this study is any analysis of the numbers of men dying of prostate cancer after a diagnosis with M1 disease as a percentage of the total numbers of men dying at the same age from all causes. We would respectfully suggest that such data would have been helpful in putting the study data into an appropriate context.

As the senior author of this study notes in a quote in the media release, “Due to a lot of natural variation in the biology of prostate cancer, [this] study should stimulate the need to develop an algorithm to identify healthy, elderly men who might benefit from an earlier diagnosis.”

With that statement we are in complete agreement. These men had clinically significant prostate cancer that needed much earlier and accurate diagnosis. Instead, they had lived with undiagnosed prostate cancer for years. There is no good reason to be surprised that they were consequently diagnosed with metastatic disease and a high risk for prostate cancer-specific mortality.

6 Responses

  1. Why would this surprise anyone? The majority of prostate cancer deaths occur in older men. The natural history of untreated prostate cancer as described by the registries of the Scandinavian countries relates the high death rate of untreated prostate cancer. Why this has been ignored by the USPSTF is part of the current mystery …

  2. But the statement to which you agree “Due to a lot of natural variation in the biology of prostate cancer, [this] study should stimulate the need to develop an algorithm to identify healthy, elderly men who might benefit from an earlier diagnosis …” supports the continued availability of some form of “testing” and “examination” for all men who fall into the age levels where prostate cancer is found to be in development, and that ranges from somewhere in the 30s for a limited amount of men to the 80s for other men. I keep reading the “will likely die of some other ailment” for men over 70 or 75. Well, would I fall in a favored category of continued PSA and DRE since my parents died in their mid-90s? I, too, could very well live to that age, so were I 70 or 75, I would still have 25 or at least 20 years of possible longevity — unless testing and examination were denied me and I ended up dying of advanced, aggressive prostate cancer because of that denial.

  3. Charles Myers just this week discussed the issue of discounting older men in relation to the USPSTF decision, among other health care evidence. The idea that older men (people) are not worth treating is ubiquitous in diseases of maturity. And if not worth treating then certainly not worth testing. A man of 65-70 is a statistic even before his demise, though he may not know it.

  4. We are all potential data points for statistical analysis. However, decisions about disease prevention and management in individuals can not and should not be made on the basis of statistics alone. The USPSTF acknowledges this very specifically.

    Just because a man is 65 or 75 does not mean that his clinical risks do not need to be identified and managed appropriately. Conversely, a man of > 65 certainly should be made aware of the fact that there are no data (to date) supporting the surgical treatment of prostate cancer in extending the overall survival of men with low-risk prostate cancer from the two large clinical trials that have studied this question. A man of 75+ years of age with low risk disease should understand that there are no data suggesting that any form of treatment will extend his survival. Men of 40-50 years of age also need to be made aware of the fact that if they do not get at least one PSA test they run the risk of being diagnosed later in life with an incurable form of prostate cancer.

    Epidemiological information can help to guide good clinical practice. It can not provide absolute guidance as to good and bad clinical practice with respect to an individual patient. The draft USPSTF recommendation is not some form of absolute dictat. It is what is says it is — a recommendation (for primary care practitioners). That recommendation is that the application of mass, annual, population-based screening of uninformed men is not currently justified for healthy American males over the age of 40 years of age. The recommendation clearly leaves the decision whether to test an individual up to the patient and his physician.

  5. I am 59 at M1, scared … Gleason 9 … one shot of Lupron so far.

  6. Kevin:

    Please consider joining our social network, through which we can connect you to other patients and help you to address your (enirely understandable) fear and concerns.


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