Prognostic correlation of cell cycle progression score and Ki-67 as a predictor of aggressiveness, biochemical failure, and mortality in men with high-risk prostate cancer treated with external beam radiation therapy

Iván Henríquez López; David Parada; Pablo Gallardo; Marina Gascón; Arnau Besora; Karla Peña; Francesc Riu; Miquel Arquez Pianetta; Oscar Abuchaibe; Laura Torres Royò; Meritxell Arenas

doi:10.1016/j.rpor.2017.02.003

Prognostic correlation of cell cycle progression score and Ki-67 as a predictor of aggressiveness, biochemical failure, and mortality in men with high-risk prostate cancer treated with external beam radiation therapy

Rep Pract Oncol Radiother. 2017 May-Jun;22(3):251-257. doi: 10.1016/j.rpor.2017.02.003. Epub 2017 Apr 26.

Affiliations

¹ Radiation Oncology Department, University Hospital of Sant Joan, Institute d'Investigació Sanitaria Pere Virgili (IISPV), Reus, Tarragona, Spain.
² Pathology Department, University Hospital of Sant Joan, Institute d'Investigació Sanitaria Pere Virgili (IISPV), Reus, Tarragona, Spain.
³ Faculty of Medicine, University Hospital of Sant Joan, Reus, Tarragona, Spain.
⁴ Bioinformatics, Institute d'Investigació Sanitaria Pere Virgili (IISPV), Reus, Tarragona, Spain.
⁵ Department of Radiation Oncology, Virgilio Galvis Ramirez Cancer Centre, Bucaramanga, Colombia.

Abstract

Objectives: Ki-67 is a proliferation marker in prostate cancer. A prognostic RNA signature was developed to characterize prostate cancer aggressiveness. The aim was to evaluate prognostic correlation of CCP and Ki-67 with biochemical failure (BF), and survival in high-risk prostate cancer patients (pts) treated with radiation therapy (RT).

Methods: CCP score and Ki-67 were derived retrospectively from pre-treatment paraffin-embedded prostate cancer tissue of 33 men diagnosed from 2002 to 2006. CCP score was calculated as an average expression of 31 CCP genes. Ki-67 was determined by IHC. Single pathologist evaluated all tissues. Factors associated to failure and survival were analyzed.

Results: Median CCP score was 0.9 (-0-1 - 2.6). CCP 0: 1 pt; CCP 1: 19 pts; CCP 2: 13 pts. Median Ki-67 was 8.9. Ki-67 cutpoint was 15.08%. BF and DSM were observed in 21% and 9%. Ki-67 ≥ 15% predicted BF (p = 0.043). With a median follow-up of 8.4 years, 10-year BF, OS, DM and DSM for CCP 1 vs. CCP 2 was 76-71% (p = 0.83), 83-73% (p = 0.86), 89-85% (p = 0.84), and 94-78% (p = 0.66). On univariate, high Ki-67 was correlated with BF (p = 0.013), OS (p = 0.023), DM (p = 0.007), and DSM (p = 0.01). On Cox MVA, high Ki-67 had a BF trend (p = 0.063). High CCP score was not correlated with DSM.

Conclusions: High Ki-67 significantly predicted outcome and provided prognostic information. CCP score may improve accuracy stratification. We did not provide prognostic correlation of CCP and DSM. It should be validated in a larger cohort of pts.

Keywords: ADT, androgen deprivation therapy; Biomarkers; CCP genes; CCP, cell cycle progression; CSS, cause-specific survival; CTCv3.0, common terminology criteria for adverse events; CTV, clinical target volume; DFS, disease-free survival; DMFS, distant metastasis free survival; FFbF, freedom from biochemical failure; GI, gastrointestinal; GU, genitourinary; Gy, gray; HE, hematoxylin and eosin; IHC, immunohistochemical; Ki-67; OS, overall survival; PCa, prostate cancer; PSA, prostate specific antigen; Prostate cancer; RT, radiation therapy; pts, patients.