Comorbidities and risk for prostate cancer-specific mortality


It is not exactly news that men who are diagnosed with localized prostate cancer, but who have a significant number of comorbid conditions, are actually at relatively low risk of prostate cancer-specific mortality. The question is whether we can get better at quantifying that risk for individual patients so that they can make better decisions about their treatment needs.

A research letter by Daskivich et al., just published in the Archives of Internal Medicine, has used a detailed questionnaire for men with localized prostate cancer to assess their likelihood of dying from other conditions. An invited commentary on the research letter is also available, and a detailed discussion of this research letter appears on MedPage Today.

Back in 2007, Litwin et al. first reported the development of the Total Illness Burden Index for Prostate Cancer (TIBI-CaP). This is an 84-question survey that a patient can supposedly complete in about 15 minutes in a doctor’s office. Litwin and his colleagues were initially able to show that men who had the highest TIBI-CaP scores were 13 times more likely to die of causes other than prostate cancer over a 3.5-year period than the men who had the lowest scores (after controlling for age, education, income, and race/ethnicity).

Now, with longer follow-up, Daskivich et al. appear to have been able to refine the predictive ability of the TIBI-PCa questionnaire.

  • The questionnaire was initially sent to 4,635 active participants in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database.
  • 2,900 men filled out the questionnaire and were followed for a median of 6.2 years.
  • Overall mortality in the study cohort was 14.5 percent.
  • Prostate cancer-specific mortality in the study cohort was 3 percent.
  • 41 percent of men whose TIBI-CaP scores were ≥ 12 died of causes other than prostate cancer
  • Only 6 percent of men whose TIBI-CaP scores were ≤ 2 died of causes other than prostate cancer.
  • Overall, the men with the highest TIBI-CaP scores were 10.3 times more likely to die of causes other than prostate cancer compared with men with the lowest scores.

The authors conclude that the presence and severity of comorbidities should be a key consideration in clinical decision-making regarding the treatment of localized prostate cancer because of the indolence of many early stage cases.

It is reasonable to note that this median follow-up of 6.2 years is still short. The authors themselves supposedly state that a survival advantage for definitive local therapy only becomes significant at 8 years after treatment. It would therefore be helpful if this study were to be continued until the median follow-up is at least 10 years or so to get greater clarification of the value of the TIBI-CaP survey.

In the invited commentary, Ablin et al. argue that PSA testing does not distinguish between potentially dangerous and less consequential prostate cancer. They suggest that the promise of early detection of prostate cancer through PSA screening has led to over-diagnosis and over-treatment for millions of men whose prostate cancers would never have metastasized.

The “New” Prostate Cancer InfoLink has no interest in re-hashing — for the 10,000th time — the prostate cancer screening discussion. We came to the conclusion some time ago that: (a) we need a better test than the PSA test to differentiate accurately between indolent and aggressive forms of prostate cancer; (b) every man is entitled to make his own decisions, in concert with his physician(s), about the merits of PSA testing in his personal case. What we are, however, very interested in is helping to get men the very best tools to allow them to make decisions about their need for treatment.

The TIBI-CaP survey appears to offer another opportunity to assist men to make good decisions. We would hope that tools like this and the CAPRA score (developed by researchers at the University of California at San Francisco) would be used by clinicians with all of their newly diagnosed patients with localized disease. Those patients need the best possible understanding of their real clinical risk of prostate cancer-specific mortality, which is commonly relatively small — particularly for men > 65 years of age with low- or very low-risk prostate cancer. In such patients, some form of expectant management (active surveillance) would often seem to be a more reasonable approach to long-term care than any form of immediate, active intervention. What we do not yet know is whether active surveillance can be a reasonable option for much younger men being diagnosed closer to 50 or 55 years of age.

It is also worth noting that a rise in PSA after local treatment does not always warrant further treatment. However, PSA kinetics can be used to assess risk in such circumstances. Data from Johns Hopkins some time ago has clearly suggested that a post-treatment PSA doubling time of < 3 months is associated with a high risk of prostate cancer-specific mortality, whereas a PSA doubling time of > 15 months carries a very low risk.

5 Responses

  1. My conclusion from the research letter is that EVERYBODY should have a PSA test (same as cholesterol blood tests); discuss with his doctor his prognosis based on the general health information, age, family history, etc.; and based on the two he should consider with his doctor the possible treatment.

    There is no such thing as “over-diagnosis.” There is only misinterpretation and over-treatment.

    The “New” Prostate Cancer InfoLink is entitled to its opinion, but that doesn’t make it right.

  2. The “New” Prostate Cancer InfoLink has never intended to either suggest or imply that we are “right” about these issues — for the simple reason that, given the available facts, “right” depends on your point of view.

    We would first note that the idea that “everyone” already gets cholesterol tests and their blood pressure taken on an annual basis (let alone any test for colon cancer on a regular basis after age 50) is simply not true at all. Many men just don’t go near a doictor at all unless they are sick — and they have a perfect right to behave that way … so long as they don’t then think they are entitled to medical miracles when they get diagnosed late with an advanced form of a disorder that would have been curable earlier.

    We would also point out that a diagnosis of prostate cancer today requires a biopsy. A biopsy is not a benign procedure. It comes with a significant risk for infection and other complications (see, for example, this link). The term “over-diagnosis” (as used by Ablin et al., not by The “New” Prostate Cancxer InfoLink) may well be an inappropriate descriptor, but then what is the correct term for the excessive and inappropriate over-use of prostate biopsy? There are certainly frequent cases of men of 80+ years of age who receive multiple biopsies on the basis of slightly elevated PSA levels but who are at very close to zero risk for any form of prostate cancer that has any clinical symptoms at all.

  3. PRE-MATURE FOLLOW-UP AGAIN

    Sitemaster, thanks for posting this interesting and important piece. This research should advance the field, but in one minor area I’m glad you criticized the authors’ comment about 8 years of follow-up being useful for seeing a survival advantage.

    Here’s the paragraph from your article above: “It is reasonable to note that this median follow-up of 6.2 years is still short. The authors themselves supposedly state that a survival advantage for definitive local therapy only becomes significant at 8 years after treatment. It would therefore be helpful if this study were to be continued until the median follow-up is at least 10 years of so to get greater clarification of the value of the TIBI-CaP survey.”

    I hope researchers will put emphasis on the “at least” part. I’m thinking of the data in the “Statistical Abstract of the United States, 2009 – Library Edition, Table 173,” on page 118 for “Cancer –Estimated New Cases, 2008, and Survival Rates: 1987-1989 to 1996-2004.” The entry for prostate cancer shows a “5-year relative survival rates (percent)” for “White” and “Black” for four periods, 1987-1989, 1990-1992, 1993-1995, and 1996-2004.

    Using just the figures for “White” men, the respective entries are 85.4%, 95.3%, 96.2%, and 99.4% (the latter for 1996-2004, the most meaningful for us at the current time).

    Using just the figures for “Black” men, the respective entries are 72.2%, 85.5%, 91.5%, and 95.9% (the latter for 1996-2004).

    Not only is survival extremely high at the 5-year point, especially for white men, but there are clear trends toward increased survival in each time snapshot. Moreover, that last snapshot spans 8 years, with half of it in the 1990s, well before many of the technologies favored today were on the scene.

    Even more encouraging, to me at least, is the finding that 95% of men with high-risk prostate cancer are alive at the TEN year point! (“Mayo Clinic Validation of the D’Amico Risk Group Classification for Predicting Survival Following Radical Prostatectomy. J Urol Vol. 179, page 1354, April 2008)

    Unfortunately for research, such survival success almost compels follow-up periods well in excess of 10 years. I’m thinking that around 15 years is a minimum unless the trial or study population is extremely large.

    I’m trying to understand what the authors could have been thinking with their statement about 8 years of follow-up being adequate. Is there something I’m missing here? Is it a matter of not realizing that survival is substantially longer with prostate cancer in this era, compared to other cancers? It would not matter much if this instance were just a one off, but this mistake seems common. Seriously, can you shed light on that? If we survivors with no enrolled medical education can see that, why can’t the researchers?

  4. TESTING EVERYONE, AND THEN …

    I like Reuven’s approach to PSA testing with one tweak (his August 10, 2010 at 10:59 am response): make sure active surveillance is adequately and positively covered in all discussions with men who should consider a biopsy but have evidence for low-risk based on PSAs and DREs. I notice that the comment by Dr. Albin gave a powerful push for active surveillance as an option.

  5. One of the best articles I’ve read in a while … from a layman.

    Nine years after my PSA @ 56, 6 months of Lupron, surgery (bad margins) followed by 40+ radiation session (10 months later), I’m 58 and still loving life.

    I’m a runner, laugh a lot, have a good job, love my wife and kids, drink and party too much. Bet they’re all high on the “good list” Cigars probably not. Next PSA test in a few days and that always makes me nervous.

    Would love to have access to the 85 questions and measurement of risk as road map for what to do / not to do.

    I’m always looking for an “edge” to beat this [expletive deleted] disease.

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