Prostate cancer screening based on prostate biopsy for men with levels of serum prostate-specific antigen (PSA) above an empirical level, or abnormal digital rectal examination (DRE), results in diagnosing many men with prostate cancer for whom the disease does not pose a threat to their life. Welch has recently calculated that there are 2.74 million US men aged 50–70 with a PSA > 2.5. If all American men in this age group had a PSA blood test, and a PSA > 2.5 is used as an indication for biopsy, this means that in the USA alone 775000 cases will be diagnosed. This is 543 000 more than the 232 000 cases diagnosed in 2005, and 25 times more than the 30 350 men expected to die of prostate cancer per year in the USA .
Several autopsy studies of men dying of other causes have documented the high prevalence of histological prostate cancer . A large proportion of this histological, or ‘latent’, prostate cancer is never destined to progress or affect the lifespan of the patient. Since the introduction of PSA screening, the lifetime risk of being diagnosed with prostate cancer has almost doubled from around 10%, in the pre-PSA era, to 17% . This means that many cases of localized prostate cancer are overtreated, in that some patients not destined to experience prostate cancer death or morbidity are subject to radical therapy .
Cancer aggressiveness can be predicted to some degree using existing clinical parameters. The ones mostly widely used are tumour grade, or Gleason score, PSA and tumour stage. Favourable risk prostate cancer is characterized as Gleason 6 or less, PSA 10 or less and T1c–T2a disease . As a result of stage migration due to PSA screening, the proportion of newly diagnosed patients who fall into the ‘favourable risk’ category has increased, and now constitutes 50–60% of patients. While patients with these characteristics have a much more favourable natural history and progression rate than those with higher Gleason grade or PSA, some of them still progress to advanced, incurable prostate cancer and death.
An update of a large group of patients in Connecticut who were treated with watchful waiting has recently reported 20-year follow-up . These data confirm the powerful predictive value of Gleason score. In that pre-PSA screening cohort, 23% of untreated Gleason 6 patients died of prostate cancer by 20 years. For Gleason 7 prostate cancer, about 65% died of prostate cancer. In addition, the author recently subjected the original slides to r-analysis using contemporary Gleason scoring . This demonstrated clearly that there has been a shift in grade interpretation over the last 20 years. Many Gleason 6 cancers diagnosed 20 years ago would be called Gleason 7 today. Thus, the Connecticut results are likely to represent a ‘worse case’ scenario for the expected mortality from ...