The Evolving Role of Prostate-Specific Membrane Antigen-Based Diagnostics and Therapeutics in Prostate Cancer

Am Soc Clin Oncol Educ Book. 2019 Jan:39:321-330. doi: 10.1200/EDBK_239187. Epub 2019 May 17.

Abstract

Prostate-specific membrane antigen (PSMA)-based imaging seeks to fill some critical gaps in prostate cancer staging and response assessment, and may select patients for treatment with radiolabeled PSMA conjugates. In biochemical recurrence, at prostate-specific antigen (PSA) levels as low as 0.2 ng/dL, 68Ga-PSMA imaging has demonstrated a 42% detection rate of occult metastatic disease, and detection has been greater than 95% when PSA levels are higher than 2 ng/dL. This may facilitate novel approaches, including salvage lymphadenectomy or metastasis-directed radiation therapy, in patients with oligometastatic disease. PSMA-based imaging has shown promise in evaluating treatment response in hormone-sensitive and castration-resistant disease; however, additional longitudinal assessment is needed given the heterogeneity in uptake changes after the initiation of androgen-deprivation therapy. Changes in uptake must be taken in context of RECIST measurements and other response parameters, given the potential for growth of PSMA-negative lesions and persistent uptake in treated bone lesions of uncertain significance. For selecting patients to receive PSMA-targeted radioconjugate therapy, standardized uptake value thresholds remain to be established. Nevertheless, preliminary data from 177Lu-PSMA theranostic trials have yielded PSA responses in up to 57% of patients, as well as pain relief and improved quality of life. Thrombocytopenia was the most common grade 3 or greater toxicity; however, grade 1 xerostomia occurred frequently and was cited as the most common reason for treatment discontinuation.

Publication types

  • Review

MeSH terms

  • Antigens, Surface / metabolism*
  • Biomarkers, Tumor*
  • Clinical Trials as Topic
  • Glutamate Carboxypeptidase II / metabolism*
  • Humans
  • Male
  • Molecular Imaging / methods
  • Molecular Targeted Therapy
  • Positron Emission Tomography Computed Tomography
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / etiology
  • Prostatic Neoplasms / therapy*
  • Radiopharmaceuticals
  • Treatment Outcome

Substances

  • Antigens, Surface
  • Biomarkers, Tumor
  • Radiopharmaceuticals
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II