Ploidy status and risk for prostate cancer-specific mortality

We have known for many years (certainly at least 20) that the presence of abnormal numbers of chromosomes (aneuploidy) in prostate cancer tumor cells is a risk factor for more serious forms of prostate cancer.

A newly published paper by Stopsack et al. in the Proceedings of the National Academy of Sciences or PNAS now suggests that it may be possible quantify this risk, and to develop a test that is specific for risk of death from prostate cancer at time of diagnosis — based on the ploidy status of pathological tissue at biopsy. Such a test, if it were to come with a high degree of accuracy, might revolutionize the way we determine which patients need immediate treatment and which patients can be monitored over extended periods of time. A discussion of this paper is also available on the HealthDay web site.

Stopsack et al. first used biopsy tissues from a cohort of 333 men with prostate cancer to develop a “signature” pattern of chromosomal gains and losses (ploidy status) within prostate cancer cells.

They than looked at data from two different cohorts prostate cancer patients (404 patients in total) who were diagnosed and followed for an average (median) of 15 years, and for whom appropriately stored, original tumor biopsy specimens where still available.

By reanalyzing the biopsy tissues from these patients and using  the accumulated clinical data they found that they could divide these 404  patients into groups based on their ploidy status, and that, compared to the patients whose tumors had no suggestion of predictable aneuploidy:

  • The 23 percent of patients whose tumors had five or more predicted chromosome arm alterations at the time of diagnosis were 5.3 times more likely to die of prostate cancer during follow-up.
  • This finding held up even in otherwise identifiable high-risk patients, when the degree of tumor aneuploidy still predicted risk for prostate cancer-specific mortality independent of any other characteristics.

Now we should be very clear that there would be a lot more work to be done before we could know that such a test could be used to predict significant risk for prostate cancer-specific mortality at time of diagnosis. It may also be that such data, when combined with other readily available data (stage, grade group, PSA level, etc.) can be used to provide an even more accurate way to project risk for prostate cancer mortality.

We also need to be aware that prostate cancer is often a multimutational disorder and so a man initially diagnosed with (say) favorable intermediate-risk prostate cancer after an initial mutational event (i.e., with a Gleason score of 3 + 4 = 7) might have a normal ploidy status at diagnosis but aneuploid status after a second mutational event). THis would imply the need to repeat testing of ploidy status over time.

However, it has long been suspected that ploidy status might be one of the keys to the identification of higher-risk forms of prostate cancer at time of diagnosis, and so this new information seems to imply a step in the right direction.

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