THE "NEW" PROSTATE CANCER INFOLINK

A presentation at the ongoing annual meeting of the European Association of Urology (EAU), in London, England, has reported (perhaps unsurprisingly) that PSA testing for risk of prostate cancer based on family history alone is not a very good idea.

The paper presented by Johnson et al. is based on data from > 82,000 men who were screened for risk of prostate cancer between 1999 and 2009 during the recruitment of men in the UK for enrollment in the ProtecT trial. (As most of our readers will be aware, the initial results of the ProtecT trial were first published last year in the New England Journal of Medicine.) The  commentary below on the presentation by Johnson et al. is based on a report on the UroToday web site.

Out of the > 82,000 patients who were screened by PSA testing, baseline data on any history of cancer among first-degree relatives (i.e., fathers and brothers only) were also collected for > 80,000 of them. Patients who had a PSA level of ≥ 3 ng/ml were referred for a TRUS-guided systematic biopsy, and those who had a positive biopsy results were invited to enroll in the ProtecT trial.

Johnson et al. used the available data to calculate the prostate cancer detection rate, risk ratio (RR), positive predictive value (PPV), and specificity of PSA testing in men with and without a family history of prostate cancer. And here is what they found:

• 4,319/73,553 men (5.9 percent) had a positive, first-degree family history of prostate cancer and 69,234 (94.1 percent) did not.
• Among the 4,319 men with a positive family history,
  • 571 (13.2 percent) had a PSA level of ≥ 3 ng/ml.
  • 234 (5.4 percent) were found to have prostate cancer tumors on biopsy.
  • PSA testing had
    • A PPV of 41 percent
    • A specificity of 91.8 percent
• Among the 69,234 men without a positive family history,
  • 7,275 (10.5 percent) had a PSA level of ≥ 3 ng/ml.
  • 3.7 percent were found to have prostate cancer tumors on biopsy.
  • PSA testing had
    • A PPV of 35 percent
    • A specificity of 92.9 percent

In other words, if only men with a positive family history for prostate cancer had been given PSA tests for risk of prostate cancer, the researchers would have missed > 90 percent of all the prostate cancers diagnosed in seeking participants for the ProtecT tral. But do remember that many of those cancers that were being diagnosed were low or very low risk.

In an additional portion of their study, Johnson et al. also reported on a subset of 1,230 prostate cancer cases and 1,528 men without prostate cancer (controls) who had agreed to complete an extended family history of prostate cancer (i.e., one that encompassed all family members of whatever degree — father and brothers but also uncles, grandfathers. etc.). In this subset analysis, the authors report the following:

• 224/1,230 prostate cancer cases (18.2 percent) reported a family history of prostate cancer (of any degree).
• Of these 224 cases
  • 170 (75.9 percent) reported a first-degree relative as having prostate cancer.
  • 80 (35.7 percent) reported a father with prostate cancer.
  • 90 (40.2 percent) reported a brother with prostate cancer.
• 146/1,528 controls (9.5 percent) reported a family history of prostate cancer (of any degree).
• Among the men with a positive family history of prostate cancer of any degree,
  • The increase in relative risk for prostate cancer compared to the controls was 1.47.
  • The greatest increase in relative risk (RR) compared to the controls was in
    • Men < 60 years of age (RR = 1.65)
    • Men with a brother who already had been diagnosed with prostate cancer (RR = 2.49)
  • A positive family history was associated with a higher risk of developing more aggressive cancer with a Gleason score ≥ 8 (RR = 2.19).

It is our understanding that there will be a lot more data to come from this screening study that may help us to better determine the relative value of population-based as opposed to selective screening for risk of prostate cancer. However, The “New” Prostate Cancer InfoLink is not at all surprised that family history is: (a) a factor in determining risk for prostate cancer, but (b) far from being the most or the only important factor.

We also note that this paper by Johnson et al. provides no insight into the type of prostate cancer diagnosed in family members. We feel relatively sure that having a first-degree relative who has or had either high-risk disease or metastatic disease is rather more important in terms of risk for clinically significant prostate cancer than having a first-degree relative who was diagnosed with low- or even intermediate-risk prostate cancer. We understand that the research team has genetic/genomic data from all the patients in the above-mentioned subset of 224 men who were diagnosed with prostate cancer. However, we may not be able to really resolve some of these issues without genetic/genomic data that spans several generations of patients and controls.

Filed under: Diagnosis, Risk | Tagged: Diagnosis, family, history, PSA, risk, testing |