A recent review concluded Gleason 6 does not meet any of the six classic hallmarks of cancer . In a series of 9557 patients with organ-confined Gleason ≤6 (without contemporary re-review) that underwent radical prostatectomy, only three died from PCa . This finding was corroborated in the Physicians Health Study, in which no patient died of Gleason ≤6 following prostatectomy after >2600 person-years of follow-up . Of course, surgery alters the natural history, and longer follow-up is mandatory; nevertheless, the available data suggest true Gleason 6 has an exceedingly low, perhaps infinitesimally small, risk of leading to death from PCa.
Does this pathologic and clinical data warrant rethinking our nomenclature? Modifications to the Gleason system are not unprecedented. Gleason patterns 1–2, described in 1966, are now considered normal variants. Perhaps a time will come when Gleason 6 is considered a risk factor for harboring higher-grade cancers that require diagnosis and treatment.
However, there are several potential pitfalls with regard to relabeling Gleason 6: understaging, missed opportunity for cure, and medical liability . Currently, the diagnosis of localized PCa can lead to a wide range of treatment-related outcomes, from life-saving to life-altering. Management decisions would be easier if the prostate was on a man's elbow.
We believe the holy grail is the elusive pathologic, radiographic, or serologic tool to definitively determine the prostate does not contain higher-grade cancers. In that setting, it would be difficult to substantiate immediate treatment of Gleason 6 cancer. In contrast, definitive identification of higher-grade cancers would warrant treatment in a large proportion of men with a reasonable life expectancy.
Conflicts of interest
S. Eggener: Myriad Genetics: research support, consultant; Genomic Health: consultant. K. Richards has nothing to disclose.
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