Ki-67 in screen-detected, low-grade, low-stage prostate cancer, relation to prostate-specific antigen doubling time, Gleason score and prostate-specific antigen relapse after radical prostatectomy

Objective. To evaluate the correlation of Ki-67 as a proliferation marker to prostate-specific antigen doubling time (PSADT), Gleason score and its possible role as a predictor of PSA relapse after radical prostatectomy in early prostate cancer (PC). Material and methods. Out of 660 patients detected with PC in the Swedish branch of the European Randomized Study of Prostate Cancer, 270 were managed with active surveillance. During follow-up (mean 63 months), 70 men were treated with radical retropubic prostatectomy (RRP). In 50 of these patients the preoperative PSADT was calculated and archive prostatectomy specimens were stained for Ki-67. The quantification of positive staining cells was performed by counting five to 15 randomly selected microscopic fields using an eyepiece graticule at 400×magnification and at least 1000 tumour cells were counted for each patient. One pathologist, blinded to the PSADT values, performed the pathological assessment. The correlation between Ki-67, PSADT and Gleason grade was explored. Cox proportional hazard model was used to evaluate the prognostic power for Ki-67 and other markers on the risk of PSA relapse after RRP. Results. Ki-67 was not correlated with PSADT (p=0.45) but was correlated with Gleason grade (p<0.0001). In the Cox proportional hazard model Ki-67 (p=0.03) [hazard ratio (HR) 2.49, 95% confidence interval (CI) 1.07–5.80] and total PSA (p=0.0068) (HR 1.86, 95% 1.19–2.92) were associated significantly with the risk of disease progression. Conclusion. In men with screen-detected, clinically low-grade, low-stage prostate cancer, Ki-67 may be a valuable prognostic marker of PSA relapse after radical prostatectomy.