Association between previous negative biopsies and lower rates of progression during active surveillance for prostate cancer

Purpose To test any-cause discontinuation and ISUP GG upgrading rates during Active Surveillance (AS) in patients that underwent previous negative biopsies (PNBs) before prostate cancer (PCa) diagnosis vs. biopsy naive patients. Methods Retrospective analysis of 961 AS patients (2008-2020). Three definitions of PNBs were used: (1) PNBs status (biopsy naive vs. PNBs); (2) number of PNBs (0 vs. 1 vs. >= 2); (3) histology at last PNB (no vs. negative vs. HGPIN/ASAP). Kaplan-Meier plots and multivariable Cox models tested any-cause and ISUP GG upgrading discontinuation rates. Results Overall, 760 (79.1%) vs. 201 (20.9%) patients were biopsy naive vs. PNBs. Specifically, 760 (79.1%) vs. 138 (14.4%) vs. 63 (6.5%) patients had 0 vs. 1 vs. >= 2 PNBs. Last, 760 (79.1%) vs. 134 (13.9%) vs. 67 (7%) patients had no vs. negative PNB vs. HGPIN/ASAP. PNBs were not associated with any-cause discontinuation rates. Conversely, PNBs were associated with lower rates of ISUP GG upgrading: (1) PNBs vs. biopsy naive (HR:0.6, p = 0.04); (2) 1 vs. 0 PNBs (HR:0.6, p = 0.1) and 2 vs. 0 PNBs, (HR:0.5, p = 0.1); (3) negative PNB vs. biopsy naive (HR:0.7, p = 0.3) and HGPIN/ASAP vs. biopsy naive (HR:0.4, p = 0.04). However, last PNB <= 18 months (HR:0.4, p = 0.02), but not last PNB > 18 months (HR:0.8, p = 0.5) were associated with lower rates of ISUP GG upgrading. Conclusion PNBs status is associated with lower rates of ISUP GG upgrading during AS for PCa. The number of PNBs and time from last PNB to PCa diagnosis (<= 18 months) appear also to be critical for patient selection.