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Prostate cancer with low PSA

Study
Results
Comment

One of the problems with screening tests for cancer is that there is an assumption that if you have a negative test, you don’t have cancer. Many people just don’t realise that you can have cancer with a negative screening test. For prostate cancer serum PSA levels of 4 μg/L or more are considered to show the possible presence of cancer. An analysis of men in a large randomised study shows that cancer is also found in men with lower levels [1].

Study

The study (Bandolier 114) enrolled men aged 55 years or older with a normal digital rectal examination, and American Urological Association score of 20 or lower (less than severe symptoms of benign prostatic hyperplasia), and a PSA of 3.0 μg/L or lower. Men were given a three-month supply of placebo tablets, and if PSA was confirmed as being 3 μg/L or lower and adherence was within 80% of nominal, they were randomised to finasteride 5 mg/day or placebo.

Men had annual measurements of PSA and digital rectal examinations, and any value above 4 μg/L or abnormal digital rectal examination during the trial prompted a recommendation for prostate biopsy.

This study only included men on placebo who never had a PSA above 4 μg/L or abnormal rectal examination, who never had a biopsy or prostate operation during the study, but who did have a prostate biopsy at the end of the seven-year trial. The presence of prostate cancer on histology, and grading, were related to the PSA value measured at the time.

Results

The minimum age was 62 years (range 62-91 years) at end of study, and about a fifth of men were aged over 75 years. Most (94%) were white, and 16% had a family history of prostate cancer, with an affected father, brother, or son. In 2,950 men with PSA values of 4 μg/L or less, 449 (15%) had prostate cancer. The rate was higher (20%) in men with family history than those without (14%).

Men with any prostate cancer were found at all levels of PSA (Figure 1), with increasing prevalence at increasing PSA. Most cancers were low grade, with 77% with Gleason score of 5 or 6, but with 15% with scores of 7 to 9, a grade usually associated with disease progression.



Figure 1: Distribution of serum PSA levels in men with any biopsy detected prostate cancer, and with high-grade (Gleason ≥7) cancer





High-grade cancers (defined as a Gleason score of 7 or above) were also found with any level of PSA (Figure 1), rising from about 1% at ≤1 μg/L to 7% at 3-4 μg/L. High-grade cancer was found more commonly among cancers with increasing PSA value. Figure 2 shows that most of the cancers found had Geason scores above 5.



Figure 2: Distribution of Gleason scores among 449 biopsy-detected prostate cancers in men with PSA ≤4 µg/L





Comment

Although the risk of finding a cancer on biopsy is directly related to PSA levels below 4 μg/L, there is no PSA value below which a man has no risk of prostate cancer. Moreover, this statement applies not just to any grade of prostate cancer, but even to high grade cancers where disease progression in the absence of treatment is to be expected.

What makes this result so telling is that it was large, was part of a randomised trial in which these men received placebo for seven years, and during which men with elevated PSA above 4 μg/L, abnormal digital rectal examination, or prostate surgery were excluded from this study. At one level, then, the implication is that this is a best-case scenario.

Its importance is that it is a harsh reminder of the failures as opposed to the benefits of screening. Older men with normal PSA values of 4 μg/L or below should still be on the lookout for warning signs, as 1 in 8 will have prostate cancer worth treating despite that normal result.

Reference:

  1. IM Thompson et al. Prevalence of prostate cancer among men with a prostate-specific antigen level of ≤4 ng per millilitre. New England Journal of Medicine 2004 350: 2239-2246.

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