PSA velocity no better than latest PSA value in screening men carrying BRCA1/2 genes

Data from the ongoing, prospective IMPACT study has shown that PSA velocity is not predictive of risk for a positive prostate cancer biopsy result in men who are carriers of the BRCA2 gene.

As we begin to learn more about how to manage risk for prostate cancer in men with a known genetic predisposition for diagnosis with this disorder, a critical factor is how physicians need to monitor such patients over time in order to identify real risk for clinically significant disease at the earliest possible stage and time.

Several years ago, Vickers and colleagues showed clearly that PSA velocity was not generally predictive for risk of a positive prostate cancer biopsy in man in general. (Although there are individual exceptions to every rule.) This group showed us that the patient’s most recent single PSA value was a better predictor of risk for a positive biopsy than the PSA velocity. Indeed, PSA velocity has now been removed from all major clinical guidelines as an indicator of the need for a prostate biopsy.

Now, in a carefully conducted, prospective clinical study, Mikropoulos et al. have shown that the same is true for men who are at higher risk for a diagnosis of prostate cancer because they are carriers of the BRCA2 gene. In fact, they were able to conclude that:

PSA is more strongly predictive of [prostate cancer] in BRCA carriers than non-carriers. We did not find evidence that PSA [velocity] aids decision-making for BRCA carriers over absolute PSA value alone.

(For those who are interested, the link above gives access to the full text of this paper by Mikropoulos et al., just published in the British Journal of Cancer.)

The study actually showed that, among a total of 1,634 study participants, all of whom came from families including hereditary carriers of the BRCA1/2 germline genes, and all of whom had at least three PSA readings of the course of the study:

  • 174/1,634 participants (10.6 percent) were given a prostate biopsy.
  • Prostate cancer was diagnosed in 45 men (i.e., 25.9 percent of the 174 men given a prostate biopsy or 2.8 percent of the 1,634 study participants)
  • In men with a PSA level of > 3.0 ng/ml, PSA velocity was not significantly associated with presence of cancer or high-grade disease.
  • PSA velocity did not add to PSA level alone for predicting time to an elevated PSA.
  • When comparing BRCA1/2 carriers to non-carriers,there was a significant interaction between
    • BRCA status and last PSA before biopsy (P = 0.031)
    • BRCA2 status and PSA velocity (P=0.024)
  • PSA velocity was not predictive of biopsy outcome in BRCA2 carriers.

This finding is important because men who are hereditary carriers of the BRCA2 gene are known to be between 2.5 and 8.6 times as likely to be diagnosed with prostate cancer compared to non-carriers. (There is still debate about whether there is any increase in risk for diagnosis with prostate cancer for men who are carriers of the BRCA1 gene, although it does seem increasingly likely that carriers of the BRCA1 gene are at higher risk for more aggressive forms of prostate cancer than non-carriers.)

Consequently, in addition to the conclusion stated earlier, the author4s also state that they

… did not find PSA [velocity] to be an independent prognostic factor in BRCA1 or BRCA2 mutation carriers and therefore for screening an absolute PSA cut-off value should preferably be used.



One Response

  1. In 2005-2007 I read an article from the Mayo Clinic regarding the increased risk for prostate cancer for men whose father had prostate cancer and a velocity greater than 0.7 ng/dl.(My dad was diagnosed at 69 with prostate cancer that had spread to bone.) I started tracing my PSA in 1994 and when the PSA velocity suddenly changed in 2006-2007 I went to my family doctor who said my PSA was normal for my age. I said OK but the velocity is a concern based on my family history. That lead to a biopsy which confirmed localized prostate cancer Gleason 6. I was treated with the CyberKnife in 2008 and my PSA has been below 0.4 ng/dl since 2010 with no lasting adverse side effects. From my experience PSA velocity is a factor to be considered with family history.

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