PSA testing has made prostate cancer screening a reality for men in many parts of the world, but its benefit for men's health continues to be debated. In men exposed to PSA testing, there has been a well-documented change in the presentation of prostate cancer with a shift towards earlier pathological stage, not without justifiable concern about over-diagnosis by prostate biopsy. Increasingly, men now diagnosed with early stage cancer have previous PSA exposure and are selected for biopsy based on PSA change in relation to cutoff values. Some recent observations suggest that PSA may no longer be an effective marker for early stage tumours, with PSA elevation failing to discriminate tumour-specific characteristics from benign gland enlargement. Traditionally, variation in pathological stage of clinically localised prostate cancer at diagnosis has related to clinical stage, PSA and biopsy Gleason grade, but with distinctions based upon these three assessments declining and an increasing proportion of organ-confined tumours at presentation, new methods of cancer detection and prognostic assessment are now required. Molecular technologies hold great promise in this respect, and in the future biomarker signatures are likely to overshadow total PSA for guiding early diagnosis and prognostic assessment. While arguments about prostate screening will continue, owing not least to its feasibility, future debate is likely to focus increasingly on technological advances and molecular profiling of these notoriously heterogeneous tumours.
