Xing Wang, Yun-Peng Jing Wang, Yi-Sheng Xiao-Yong Zeng We performed this study to investigate pathological upgrading from biopsy to prostatectomy and clinicopathological factors associated with grade group (GG) upgrading in patients with International Society of Urological Pathology (ISUP) GG 1 and 2 prostate cancer (PCa) in a Chinese cohort. We included patients diagnosed with PCa with ISUP GG 1 and 2 at biopsy, who underwent RP at our institution. Pre-and postoperative clinical variables were examined. Univariate and multivariate logistic regression analyses were conducted to identify independent factors associated with GG upgrading. Patients in GG upgraded group had higher total prostate specific antigen (tPSA; median: 14.43 ng ml-1 vs 10.52 ng ml-1, P = 0.001) and PSA density (PSAD; median: 0.45 ng ml-2 vs 0.27 ng ml-2, P < 0.001) than those in GG nonupgraded group. Patients in upgraded group had a higher ratio for Prostate Imaging Reporting and Data System (PI-RADS) score > 3 (86.4% vs 67.9%, P < 0.001). Those with GG 1 in biopsy were more likely to experience GG upgrading after RP than those with GG 2 (71 vs 54, P = 0.016). Independent preoperative factors predicting GG upgrading were PI-RADS score > 3 (odds ratio [OR]: 2.471, 95% confidence interval [CI]: 1.132-5.393; P = 0.023), higher PSAD (P = 0.001), and GG in biopsy (OR: 0.241, 95% CI: 0.123-0.471; P < 0.001). The histopathological analyses of RP specimens revealed that perineural invasion (PNI; OR: 1.839, 95% CI: 1.027-3.490; P = 0.041) was identified as an independent factor associated with GG upgrading. Our results revealed that GG in the biopsy, PSAD, PI-RADS score > 3, and PNI were independent factors of GG upgrading. These factors should be considered for patients with ISUP grade <= 2 PCa.