Gleason Score — Prostate Cancer Architecture Grading

Developed by Dr Donald Gleason, the Gleason grading system evaluates the architectural patterns of prostate carcinoma rather than individual cellular atypia. Pathologists assess glandular structure under light microscopy, assigning a primary grade (from 1 to 5) to the most predominant architectural pattern and a secondary grade to the second most common pattern. In contemporary practice, patterns 1 and 2 are rarely reported, with diagnostic patterns ranging from 3 (well-differentiated) to 5 (poorly differentiated or undifferentiated).

The two pattern grades are summed to yield the total Gleason score, ranging from 6 to 10. To simplify interpretation and avoid patient confusion regarding a 'score of 6 out of 10' representing low-risk disease, the International Society of Urological Pathology (ISUP) introduced Grade Groups 1 to 5, mapping directly to Gleason scores 6 through 9–10.

The Gleason score is one of the most powerful prognostic indicators in prostate cancer management. Combined with prostate-specific antigen (PSA) blood levels and clinical staging, it categorises prostate cancer into distinct risk tiers (such as very low, low, intermediate, or high risk). This risk stratification directly dictates whether a patient can safely pursue active surveillance—avoiding treatment side effects like urinary incontinence or erectile dysfunction—or requires definitive intervention such as radical prostatectomy or radiation therapy combined with hormone suppression.

The Gleason score is determined by microscopic histopathological evaluation of formalin-fixed, haematoxylin and eosin (H&E) stained prostate core tissue samples. Immunohistochemical biomarkers such as p63, high molecular weight cytokeratins (HMWCK), and racemase (AMACR) may be utilised to confirm malignancy and glandular architecture. Molecular genomic assays, such as Decipher or Oncotype DX, are increasingly tested alongside Gleason scores to refine risk evaluation.

The Gleason score is used exclusively for evaluating adenocarcinoma of the prostate gland. It is not applied to other malignancies or non-adenocarcinoma prostate variants, such as small cell neuroendocrine prostate carcinoma. It is reported on tissue retrieved from transrectal or transperineal core needle prostate biopsies, transurethral resections of the prostate (TURP), and radical prostatectomy surgical specimens.

Gleason score directly guides therapy selection. A Gleason score of 6 (Grade Group 1) often qualifies patients for active surveillance, involving routine PSA tests, repeat biopsies, and MRIs without immediate therapy. Gleason score 7 (Grade Group 2 or 3) represents intermediate risk, typically managed with external beam radiotherapy, brachytherapy, or radical prostatectomy. Gleason scores 8 to 10 (Grade Groups 4 and 5) represent high-risk disease, frequently requiring multimodality treatment, including surgery or radiotherapy combined with androgen deprivation therapy.