Prostate-Specific Membrane Antigen Expression in Colorectal Cancer and Its Potential Implication in Disease Monitoring in Rectal Cancer.

Purpose: Prostate-specific membrane antigen (PSMA) is expressed in tumor-associated vessels of diverse malignancies, such as colorectal cancer (CRC). PSMA-targeted approaches show promise for diagnosing, treating, and assessing therapy response in non-prostatic cancer. Disease monitoring following neoadjuvant chemoradiation (CRT) is especially important in rectal cancer.

Methods: Firstly, clinical and histologic features of untreated CRC (n = 237; 54 from rectum) were examined for their association with PSMA expression. Secondly, rectal cancer cases following neoadjuvant CRT (n = 45) were retrieved to assess the relationship between PSMA expression, downstaging, and tumor volume reduction and were compared with untreated rectal cancers (n = 54).

Results: In untreated CRC, PSMA expression was negatively associated with pTNM stage, pT stage, pN stage, tumor deposit presence and count, and post-op adjuvant therapy administration. Higher PSMA expression was correlated with shorter overall survival when pTNM stage was controlled. In the treated rectal cancer group, advanced pTNM stage was associated with a reduced PSMA expression. In addition, treated rectal cancers showed lower PSMA expression than untreated rectal cancers. While PSMA levels correlated with tumor volume reduction and downstaging following CRT, this association was lost in stage-matched analysis.

Conclusion: PSMA expression was lower in more advanced CRCs, and the trend persisted in treated rectal cancer. After adjusting for pTNM stage, higher PSMA expression was predictive of reduced overall survival. Post-CRT PSMA level was associated with downstaging and pathologic tumor volume reduction in rectal cancer. Further studies are needed to assess the clinical value of PSMA-directed approaches in CRC management.