We would like to thank the authors for producing this informative, data-rich work. However, their specific highlighting of a small part of those data referring to cancer of Gleason score 6 developing into a lethal disease might lead to ongoing unnecessary overtreatment of patients with localized cancer. Although, at face value, 7 deaths occurring among patients with a Gleason score ≤ 6 confirmed on radical prostatectomy may support their proposition, it is important to examine the problems in methodology before making or accepting such a conclusion.
First, the processing technique used on the prostatectomy specimen was not detailed. Were these whole-mount, 3-mm step-sections? Were all slices examined or were alternate slices donated for basic research, as is often practiced in tertiary research centers? Second, although not all biopsy and prostatectomy cases were reviewed by the same pathologist, it is not stated whether the 7 deaths from apparently pure Gleason score ≤ 6 disease were part of the 27 cases that were not centrally reviewed. This error can be significant because there is moderate interobserver pathology variability. Third, the local biopsy processing and particularly biopsy sectioning were not given, because sectioning at different levels affects whether an area with a Gleason score ≥ 7 is found on biopsy. Fourth, there is growing evidence that lesion volume is a predictor of treatment failure,[3-5] which is not considered in the report by Nakabayashi et al. Fifth, there are no details provided regarding the biopsy technique (density of sampling) used to derive the histological grading. Were they targeted or randomly acquired? Did an experienced operator perform them? Transrectal ultrasound-guided biopsies can undergrade disease in approximately 30% of cases due to random error.
Although low-grade tumors may rarely progress, to the best of our knowledge the current data do not strongly support this theory. Therefore, the ongoing treatment of men with accurately characterized Gleason score 6 disease just because it might very rarely metastasize can only lead to a lack of correction in the current pathway. There is an urgent need to address the overdiagnosis and overtreatment burdens inherent in the current cancer pathway through the greater and judicious use of active surveillance in men with well-characterized Gleason score 6 disease.