Alejandro Berlin1, Julio F Castro-Mesta2, Laura Rodriguez-Romo2, David Hernandez-Barajas2, Juan F González-Guerrero2, Iván A Rodríguez-Fernández2, Galileo González-Conchas2, Adrian Verdines-Perez2, Francisco E Vera-Badillo3. 1. Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada. 2. Centro Universitario Contra el Cáncer, Hospital Universitario, Universidad Autónoma de Nuevo León, Monterrey, México. 3. Centro Universitario Contra el Cáncer, Hospital Universitario, Universidad Autónoma de Nuevo León, Monterrey, México; Department of Medical Oncology, Faculty of Medicine, Queen's University, Kingston, Ontario, Canada. Electronic address: fverabadillo@ctg.queensu.ca.
Abstract
BACKGROUND: Ki-67 for quantifying tumor proliferation is widely used. In localized prostate cancer (PCa), despite a suggested predictive role of Ki-67 for outcomes after therapies, it has not been incorporated into clinical practice. Herein, we conduct a systematic review and meta-analysis of the literature reporting the association of Ki-67 and disease outcomes in PCa treated radically. METHODS: Medline and EMBASE databases were searched without date or language restrictions, using "KI67" and "prostate cancer" MeSH terms. Studies reporting Ki-67 association with clinical outcomes (disease-free survival [DFS], biochemical failure-free survival, rate of distant metastases [DM], disease-specific survival [DSS], or overall survival [OS], or all of these) in patients with PCa managed actively were included, and relevant data extracted by 2 independent reviewers. Odds ratios (OR) were weighted and pooled in a meta-analysis using Mantel-Haenszel random-effect modeling. RESULTS: Twenty-one studies comprising 5,419 patients met eligibility for analysis, and 67.6% of patients had low Ki-67. Mean Ki-67 was 6.14%. High Ki-67 was strongly associated with worse clinical outcomes. DFS was better in those patients with low Ki-67 at 5 and 10 years (OR = 0.32, 95% CI: 0.23-0.44, P<0.00001; OR = 0.31, 95% CI: 0.20-0.48, P<0.00001). Similarly, low Ki-67 was related to improved DSS at 5 and 10 years (OR = 0.15, 95% CI: 0.10-0.21, P<0.00001; OR = 0.16, 95% CI: 0.06-0.40, P<0.00001). Association between low Ki-67 scores with improved OS (OR = 0.47; 95% CI: 0.37-0.61; P<0.00001) and high Ki-67 scores with DM at 5 years (OR = 4.07; 95% CI: 2.52-6.58; P<0.00001) was consistently observed. CONCLUSIONS: High Ki-67 expression in localized PCa is a factor of poor prognosis for DSS, biochemical failure-free survival, DFS, DM, and OS after curative-intent treatments. Incorporation into clinical routine of this widely available and standardized biomarker should be strongly considered.
BACKGROUND: Ki-67 for quantifying tumor proliferation is widely used. In localized prostate cancer (PCa), despite a suggested predictive role of Ki-67 for outcomes after therapies, it has not been incorporated into clinical practice. Herein, we conduct a systematic review and meta-analysis of the literature reporting the association of Ki-67 and disease outcomes in PCa treated radically. METHODS: Medline and EMBASE databases were searched without date or language restrictions, using "KI67" and "prostate cancer" MeSH terms. Studies reporting Ki-67 association with clinical outcomes (disease-free survival [DFS], biochemical failure-free survival, rate of distant metastases [DM], disease-specific survival [DSS], or overall survival [OS], or all of these) in patients with PCa managed actively were included, and relevant data extracted by 2 independent reviewers. Odds ratios (OR) were weighted and pooled in a meta-analysis using Mantel-Haenszel random-effect modeling. RESULTS: Twenty-one studies comprising 5,419 patients met eligibility for analysis, and 67.6% of patients had low Ki-67. Mean Ki-67 was 6.14%. High Ki-67 was strongly associated with worse clinical outcomes. DFS was better in those patients with low Ki-67 at 5 and 10 years (OR = 0.32, 95% CI: 0.23-0.44, P<0.00001; OR = 0.31, 95% CI: 0.20-0.48, P<0.00001). Similarly, low Ki-67 was related to improved DSS at 5 and 10 years (OR = 0.15, 95% CI: 0.10-0.21, P<0.00001; OR = 0.16, 95% CI: 0.06-0.40, P<0.00001). Association between low Ki-67 scores with improved OS (OR = 0.47; 95% CI: 0.37-0.61; P<0.00001) and high Ki-67 scores with DM at 5 years (OR = 4.07; 95% CI: 2.52-6.58; P<0.00001) was consistently observed. CONCLUSIONS: High Ki-67 expression in localized PCa is a factor of poor prognosis for DSS, biochemical failure-free survival, DFS, DM, and OS after curative-intent treatments. Incorporation into clinical routine of this widely available and standardized biomarker should be strongly considered.
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