269P - Prostate cancer harboring low COMT expression correlates with a poor prognosis and response to enzalutamide

Background

The enzyme catechol-O-methyltransferase (COMT) inhibits the prognosis of prostate cancer (PCa). There has been no biomarker that aids in the selection of a therapeutic agent among new-generation androgen receptor-axis targeted (ARAT) therapy, such as abiraterone (ABI) or enzalutamide (ENZ). Therefore, we aimed to assess the possibility of using COMT expression as a biomarker for PCa progression and the criteria for selecting ABI or ENZ.

Methods

We retrospectively evaluated 60 patients with PCa treated with ABI or ENZ via needle biopsy or radical prostatectomy at Iwate Medical University. Immunostaining of COMT was performed using formalin-fixed, paraffin-embedded blocks obtained from the initial prostate biopsy for diagnosis or prostatectomy. Immunostaining evaluations were scored by immunostaining intensity (0–3) and staining area (0–3) and the score ≥4 was defined as “high expression” and the score <4 was defined as “low expression.” The associations between COMT expression levels and clinical outcomes, including the duration of ENZ or ABI response, were also assessed.

Results

Of the 60 cases, nine (15%) showed low expression. Overall survival (OS) was significantly shorter in patients with lower COMT expression (hazard ratio [HR] = 0.24, 95% confidence interval [CI] 0.07–0.83, P= 0.024). When ENZ was administered as the first ARAT, progression-free survival (PFS) was significantly different between patients with COMT expression scores <4 and ≥4 (median 5.9 and 23.3 months, respectively). However, when the patients were administered ABI as the first ARAT, the PFS of the patients who underwent ARAT therapy showed no significant difference between COMT expression scores <4 and ≥4.

Conclusions

Patients with lower COMT expression have a significantly poorer prognosis for PCa. In addition, the post-ENZ administration PFS, as the first ARAT, correlated with COMT expression levels. This study is the first report on an association between COMT expression levels and the duration of ARAT.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.