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Prostate-Specific Membrane Antigen Expression in Colorectal Cancer and Its Potential Implication in Disease
Eundong Park1, Xin Wang1, Michel Kmeid2
1Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA.
Journal of Gastrointestinal Cancer
|July 19, 2025
Summary
Prostate-specific membrane antigen (PSMA) expression in colorectal cancer (CRC) correlates with survival and treatment response. Lower PSMA levels indicate advanced disease and poorer outcomes, but PSMA may help monitor rectal cancer treatment effectiveness.
Area of Science:
- Oncology
- Molecular Imaging
- Cancer Biomarkers
Background:
- Prostate-specific membrane antigen (PSMA) is expressed in tumor-associated neovasculature across various cancers, including colorectal cancer (CRC).
- PSMA-targeted agents offer potential for diagnosis, therapy, and response assessment in non-prostatic malignancies.
- Monitoring disease progression and treatment response, particularly after neoadjuvant chemoradiation (CRT) in rectal cancer, is clinically significant.
Purpose of the Study:
- To investigate the association between PSMA expression and clinicohistologic features in untreated colorectal cancer (CRC).
- To evaluate the relationship between PSMA expression, tumor downstaging, and volume reduction following neoadjuvant chemoradiation (CRT) in rectal cancer.
- To compare PSMA expression in treated versus untreated rectal cancer.
Main Methods:
- Analysis of PSMA expression in relation to clinical and histologic features in 237 untreated CRC cases (54 rectal).
- Retrospective analysis of 45 rectal cancer cases post-neoadjuvant CRT to assess PSMA expression, downstaging, and tumor volume reduction.
- Comparison of PSMA expression between treated (n=45) and untreated (n=54) rectal cancer cohorts.
Main Results:
- In untreated CRC, PSMA expression inversely correlated with advanced pTNM stage, pT stage, pN stage, and tumor deposits.
- Higher PSMA expression was linked to shorter overall survival, independent of pTNM stage.
- In treated rectal cancer, advanced pTNM stage correlated with reduced PSMA expression, and treated tumors showed lower PSMA than untreated ones.
- PSMA levels correlated with tumor volume reduction and downstaging post-CRT, but this association diminished in stage-matched comparisons.
Conclusions:
- PSMA expression is lower in advanced colorectal and rectal cancers, with a trend persisting after neoadjuvant CRT.
- Elevated PSMA expression, even after adjusting for stage, predicts reduced overall survival in CRC.
- Post-CRT PSMA levels correlate with treatment-induced downstaging and tumor volume reduction in rectal cancer, warranting further investigation into PSMA-directed strategies for CRC management.
