Tumour markers in patients on deferred treatment: prostate specific antigen doubling times

Evidence is presented that cancer which is clinically confined to the prostate follows a predictable natural course. Biological aggressiveness of prostate cancer is directly related to tumour volume, and tumour volume is proportional to serum prostate specific antigen (PSA). Thus, the increase in PSA with time in patients on deferred treatment should reflect the growth rate (doubling time) of prostate cancer. In 43 untreated patients with prostatic carcinomas, serum PSA was serially determined over an average time span of 30 months. Log-PSA values were plotted versus time, tested for linearity and compared between different clinical stages and histological grades. The increase in serum PSA was exponential (log-linear) throughout the measured interval. This linearity allowed us to calculate a PSA doubling time. For clinically localized cancers, the median doubling time was 4 years. Doubling times were faster in patients with higher clinical stages and worse histological grades. Tumour doubling times were overestimated in patients with large volume benign prostatic hyperplasia, since hyperplasia also increases serum PSA, albeit 12 times less than cancer. We conclude that prostate cancer follows a constant (log-linear) growth pattern with a doubling time that is very slow. This extraordinarily long doubling time may explain the favourable outcome of patients with low grade tumours on deferred treatment. Furthermore, this slow doubling time has important implications for early detection of prostate cancer.