Objective:To investigate the risk factors for Gleason score upgrading after radical prostatectomy in clinical low-risk prostate cancer patients aged≥65 years.Methods:A total of 485 clinical low-risk prostate cancer patients aged≥65 years at five centers of the national multi-center PC-follow database from January 2015 to March 2019 were retrospectively analyzed.Data including age at diagnosis, prostate-specific antigen(PSA), MRI prostate imaging, puncture Gleason score, operation method, puncture method, positive incision margin and capsule penetration were collected.Differences in Gleason scores before and after operation were compared, and the risk factors for Gleason score upgrading after radical resection were evaluated by univariate and multivariate Logistic regression analysis.Results:Of 485 patients with a puncture Gleason score of 3+ 3=6, 261(53.8%)cases had postoperative pathological upgrading, in whom 228(87.4%)cases had Gleason score upgrading of 7, 22(8.4%)had Gleason score upgrading of 8, and 11(4.2%)had Gleason score upgrading of 9 or more.The rate of Gleason score upgrading was elevated with increased preoperative PSA levels, positive pelvic MRI, and higher positive rates of puncture biopsy.The incidences of postoperative capsule penetration(27.2% vs.12.5%, P<0.001)and positive incision margin(25.2% vs.17.4%, P=0.036)had statistically significant differences between the pathologically upgraded group and the pathologically non-upgraded group.Multivariate analysis showed that preoperative PSA level, percentage of positive puncture biopsies, biopsy Gleason score and pelvic MRI were independent predictors of prostate cancer. Conclusions:For clinical low-risk prostate cancer patients aged≥65 years with high risk factors for Gleason score upgrading, repeated biopsies should be carried out when necessary and the treatment plan should be adjusted accordingly.