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JU INSIGHT: Prostate-Specific Membrane Antigen Is a Biomarker for Residual Disease following Neoadjuvant Intense Androgen Deprivation Therapy in Prostate Cancer

By: John R. Bright, BS; Rosina T. Lis, MD; Anson T. Ku, PhD; Nicholas T. Terrigino, BS; Nichelle C. Whitlock, PhD, MPH; Shana Y. Trostel, BS; Nicole V. Carrabba, BS; Stephanie A. Harmon, PhD; Baris Turkbey, MD; Scott Wilkinson, PhD; Adam G. Sowalsky, PhD | Posted on: 01 Jul 2022

Bright JR, Lis RT, Ku AT et al: Prostate-specific membrane antigen is a biomarker for residual disease following neoadjuvant intense androgen deprivation therapy in prostate cancer. 208: 90.

Study Need and Importance

Patients with intermediate- to high-risk prostate cancer may be offered neoadjuvant hormonal therapies prior to radical prostatectomy. In a recent clinical trial where neoadjuvant hormonal therapy was intensified by the addition of the androgen receptor pathway inhibitor enzalutamide, treatment response was measured by the volume of tumor remaining in the prostate. Patients with less than 0.05 cm3 residual disease are expected to have prolonged durations of biochemical recurrence-free survival. However, meticulous examination of prostatectomy tissue after surgery may be required for accurate quantification of remaining cancer cells, which can be confounded by treatment effects that may further limit the utility of routine hematoxylin and eosin staining and standard prostate cancer immunohistochemical markers.

“In a recent clinical trial where neoadjuvant hormonal therapy was intensified by the addition of the androgen receptor pathway inhibitor enzalutamide, treatment response was measured by the volume of tumor remaining in the prostate.”

What We Found

Following 6 months of neoadjuvant androgen deprivation therapy plus enzalutamide, in 35 patients, we observed that immunohistochemistry (IHC) with antibodies against prostate-specific membrane antigen (PSMA) demonstrated 96% sensitivity for residual tumor cells (see figure). In addition, anti-PSMA IHC was 82% specific for tumor. By contrast, in a control untreated cohort (37) anti-PSMA IHC was only 28% specific for tumor (see Figure). Positive staining in both cohorts was positively correlated (r=0.67) with gene expression measured by whole transcriptome sequencing.

“While matched biopsies may have been preferable for within-person comparisons, we were limited by the fact that most biopsies would not have harbored enough glands for robust analyses.”
Figure. Representative immunostaining of anti-PSMA IHC of benign and tumor prostate glands in treated and untreated cases. Bar: 50 μm.

Limitations

Our data come from a single-center, single-arm, phase 2 clinical trial with an independent control cohort. While matched biopsies may have been preferable for within-person comparisons, we were limited by the fact that most biopsies would not have harbored enough glands for robust analyses.

Interpretation for Patient Care

Anti-PSMA should be considered as a standard immunohistochemical marker when evaluating prostate tumors following neoadjuvant hormone therapies. This is especially appropriate for cases with difficult-to-detect residual tumors and for determining whether a patient may benefit from adjuvant systemic therapies after surgery.