Introduction

Docetaxel-based chemotherapy is recommended as first-line standard of care for metastatic castration-resistant prostate cancer (mCRPC). However, most of the patients developed treatment resistance and experienced treatment-related toxicity. Therefore, we constructed tissue microarrays using prostate biopsy samples and carried out immunohistochemistry (IHC) analyses to evaluate the clinical utility of ERG and SOX9 as potential biomarkers of docetaxel response in mCRPC patients.

Methods

We reviewed 71 patients diagnosed with mCRPC and treated with docetaxel (75mg/m2 intravenously, every 3 weeks) between 2001 and 2013. We evaluated the prostate specific antigen (PSA) response rate, PSA progression-free survival (PSA-PFS), clinical/radiologic PFS (C/R-PFS) and the overall survival (OS) based on the recommendations of the Prostate Cancer Working Group 2. The intensities of ERG and SOX9 expression in tumor cells were scored using a four-tiered grading system. A sample with more than 5% of total stained area scoring 2+ or 3+ in intensity was considered to be positive. Kaplan-Meier survival curves were constructed to illustrate the PSA-PFS, C/R-PFS and OS. Multivariate Cox proportional hazard models were utilized to estimate associations between the PSA-PFS, C/R-PFS, OS and risk factors of interest.

Results

ERG and SOX9 were found in 13 (18.3%) and 62 (87.3%) patients, respectively. ERG-positive had lower PSA response rates than negative (15.4% vs 62.1%, p = 0.004), and SOX9 showed a same trend (46.8% vs 100.0%, p = 0.003). ERG positivity correlated with a lower PSA-PFS (3.2 mos vs 7.4 mos, p < 0.001), C/R-PFS (3.8 mos vs 9.0 mos, p < 0.001) and OS (10.8 mos vs 21.4 mos, p < 0.001). SOX9 positivity also showed a lower PSA-PFS, C/R-PFS and OS (p =0.006, p =0.012 and p =0.023, respectively). On multivariate analysis, ERG positivity was a significant risk factor for a lower PSA-PFS (p < 0.001, hazard ratio (HR): 6.00, 95% confidence interval (CI): 2.96-12.16), C/R-PFS (p < 0.001, HR: 5.50, 95% CI: 2.68-11.29) and OS (p = 0.001, HR: 3.31, 95% CI: 1.66-6.64). In addition, SOX9 was also a significant risk factor for a decreased PSA-PFS (p = 0.018, HR: 2.75, 95% CI: 1.19-6.32), C/R-PFS (p = 0.025, HR: 2.44, 95% CI: 1.12-5.30) and OS (p = 0.047, HR: 4.30, 95% CI: 1.02-18.16).

Conclusions

IHC-detected ERG and SOX9 expression is significantly associated with lower PSA-PFS, C/R-PFS and OS in patients with mCRPC treated with docetaxel. They could be used as potential biomarkers for prediction to docetaxel treatment in mCRPC patients.

Funding

None