Clinical and molecular rationale to retain the cancer descriptor for Gleason score 6 disease

Treatment choices for men with indolent prostate cancer include active surveillance or definitive local therapy. Overtreatment of these patients is an important current problem. Treatment decisions are often made jointly by the clinician and the patient, partly based on the tumour's Gleason score. To reduce the burden of overtreatment, the clinical significance of Gleason score 3 + 3 = 6 prostate cancer has been questioned and some have advocated that Gleason pattern 3 should be stripped of its cancer status. However, removing the cancer descriptor would have far-reaching clinical consequences that might result in poor patient outcomes, as the evidence of a lack of malignancy is inconclusive in several areas. For example, molecular data suggest that the genomic instability underlying tumour progression precedes histologically visible changes and the absolute risk of metastasis or mortality from Gleason score 6 prostate cancer is not zero. Extreme caution is required when weighing a decision to reclassify Gleason pattern 3 disease as a non-cancer.