Risk levels and family history of prostate cancer: data from the Swiss cohort of the ERSPC

Data just published in BJU International have recently suggested that men with a known, positive family history of prostate cancer are certainly at increased risk of low-grade prostate cancer compared to men with no known family history — but not at increased risk of aggressive prostate cancer.

The new paper by Randazzo et al. is based on a detailed re-analysis of data from all of the participants in the screening arm of the Swiss cohort of the European Randomized Study of Screening for Prostate Cancer (ERSPC), who all received systematic PSA tests every 4 years. Any man in this arm of the study who was reported to have one or more first-degree relatives (i.e., a father or brother) who had been diagnosed with prostate cancer was classified as having a positive family history of prostate cancer. Patients in this cohort were given biopsies for risk of prostate cancer if their PSA level reached a threshold level of 3 ng/ml.

The key data from the re-analysis reported by Randazzo et al. are as follows:

  • The study cohort included 4,932 men with an average (median) age of 60.9 years.
  • 334/4,932 men (6.8 percent) reported a positive family history of prostate cancer.
  • The average (median) follow-up duration was 11.6 years.
  • Cumulative prostate cancer incidence was
    • 60/334 (18 percent) among the men with a positive family history
    • 550/4,598 (12 percent), among the men with a negative family history
    • This represents an odds ratio (OR) =1.6 (P = 0.001).
  • Most prostate cancers diagnosed were low grade, regardless of family history.
  • There were no significant differences in PSA level at diagnosis, biopsy Gleason score, or pathological Gleason score among patients treated by radical prostatectomy between the two groups.
  • On multivariable analysis, the following were independent predictors of overall risk for prostate cancer diagnosis:
    • Age  — hazard ratio (HR) = 1.04 (P < 0.001)
    • Baseline PSA level  — HR = 1.13 (P < 0.001)
    • Family history — HR = 1.6 (P < 0.001)
  • Baseline PSA level (HR = 1.14, P < 0.001) was the only independent predictor of prostate cancer with a Gleason score ≥ 7 on prostate biopsy.
  • The proportion of interval prostate cancer diagnosed in between the screening rounds was not significantly different.

In addition to the conclusion that family history was not associated with any increase in risk for diagnosis with aggressive prostate cancer, the authors also conclude that, regardless of family history, the PSA-based screening protocol used in the Swiss arm of the ERSPC setting detected the majority of aggressive prostate cancers and missed only a minority of interval cancers with a 4-year screening algorithm.

The “New” Prostate Cancer InfoLink has long suspected that the general increase in risk for a diagnosis with prostate cancer among men with a family history of the disease was more likely to be an increase in risk for diagnosis with low-risk disease than an increase in risk for clinically more aggressive and significant forms of prostate cancer. This makes perfect sense from a statistical and an epidemiological point of view. As far as The “New” Prostate Cancer InfoLink is aware, this is the first time that such information has been reported and published.

On the other hand, what we still don’t really have good knowledge about is whether having a first-degree relative who had a more aggressive form of prostate cancer that progressed to metastatic disease (or led to the death of that relative) places a man at similarly increased risk of diagnosis with unfavorable intermediate-risk or high-risk disease.

One Response

  1. Their main finding regarding family risk is reassuring.

    However, the detail about the 4-year screening interval would be welcome. For men with short doubling times, 4 years in the screening interval offers a very long period for the cancer to become well established and perhaps undergo even more aggressive mutation. These short doubling time cancers would logically seem to be a priority objective for screening, as they obviously have an enhanced potential for lethality or at least highly burdensome treatment (with side effects) to fight the disease.

    All but one of the countries participating in the ERSPC used a 4-year screening interval; the exception was Sweden, which used a 2-year interval. The best interval for screening is being studied, though in the ERSPC results are still quite premature, even at 13 years of follow-up, which equated, per the 13 year report, to median follow-ups since diagnosis of just 6.4 years in the intervention (screening intent) group and 4.3 years in the control group. Longer follow-up can be expected to increase the benefit of screening, and I suspect that will also increasingly favor the Swedish 2-year screening interval versus the 4-year interval in other country cohorts.

    While a 4-year interval is likely good enough for men with highly favorable initial screening PSA levels, it looks too loose for men who might have aggressive cancer, such as men like me. Such aggressive cancers with short doubling times obviously develop fast and, if unchecked, can lead to very high PSAs — indicating a challenging case — quickly.

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