Evaluation of the Proliferation Marker Ki-67 for Improved Risk Stratification of Prostate Cancer Patients Under Active Surveillance.

Background/Objectives: Active surveillance (AS) is a viable option for patients with low-risk/low-burden prostate cancer (PCa). Approximately 40-50% of patients will develop disease progression and conversion to active treatment. Therefore, better risk stratification may aid patients and urologists to improve decision making. Herein, the proliferation marker Ki-67 was examined for its prognostic potential in AS patients. Methods: Fifty-nine patients were included. Median follow-up time was 58 months (range, 10-162 months). Tumor-bearing biopsies were evaluated using immunohistochemistry (IHC) staining for Ki-67 and evaluated using digital imaging analysis to determine the percentage of Ki-67-positive PCa cells per biopsy. Results: Thirty-three of 59 patients (55.9%) developed progression. Thirty-one of 59 patients (52.5%) showed Ki-67-positive biopsies (median 0.8%; range, 0-11.9%). The median of Ki-67-positive cells was 1.5% (range, 0-11.9%) in patients with and 0% (range, 0-6.3%) in patients without progression. Comparing patients with Ki-67-positive and Ki-67-negative biopsies showed a worse progression free survival (PFS) in patients with Ki-67-positive biopsies after a period of 15 months, however, without reaching statistical significance (p = 0.071). A 5% threshold for Ki-67 positivity led to a significant difference in PFS. Further exploratory analysis revealed that patients with Ki-67-positive biopsies and aged ≥65 years or with >1 tumor-bearing biopsy show a significantly worse outcome (p = 0.038 and p = 0.037, respectively). Conclusions: Our results suggest that patients with Ki-67-positive biopsies remaining in AS for >1 year have an increased risk for PCa progression and conversion to treatment. Studies to further confirm Ki-67 as a marker for risk stratification, especially with a positivity cut-off of 5%, are warranted in larger cohorts of AS patients.