Prostate-Specific Membrane Antigen Ligand Positron-Emission Tomography in Men with Nonmetastatic Castration-Resistant Prostate Cancer - Beyond the Abstract

Treatment options for non-metastatic castration resistant prostate cancer (nmCRPC) expanded considerably with the completion of SPARTAN, PROSPER and ARAMIS trials. Novel androgen receptor inhibitors have shown improved outcomes for nmCRPC patients at risk for the development of metastases.1-3 In all of these studies, the absence of metastases was assessed by virtue of conventional cross-sectional imaging and bone scan. However, the sensitivity of conventional imaging is limited, especially in patients with low PSA values.4 Yet, with the advent of prostate-specific membrane antigen positron-emission tomography (PSMA-PET) there is a new, considerably more accurate imaging modality with higher detection rates and superior specificity.4, 5 This may lead to upstaging through the detection of distant metastases in patients that are non-metastatic by conventional imaging with potential changes in patient management.

In this multicenter study, we assessed potential upstaging by PSMA-PET in a nmCRPC patient cohort with a higher risk for the development of metastases either by PSA doubling time or Gleason score.

PSMA-PET detected any disease in nearly all patients and metastatic disease in 55% of patients with nmCRPC as assessed by conventional imaging thereby redefining the patient population through considerable stage migration. The retrospective study design does not allow to draw definite conclusions on the impact on patient management. However, the enormous shift in patient stage calls for the implementation of PSMA-PET for baseline and follow-up assessments in future clinical trials to evaluate patient stratification and treatment response with endpoints such as MFS or PFS.

On the other hand, the presence of distant metastases on PSMA-PET should not preclude patients from receiving androgen receptor inhibitor treatment as an improved outcome has been observed in patient cohorts staged by conventional imaging.

Written by: Wolfgang P. Fendler, Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen  and Manuel Weber, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen.

References:

  1. Fizazi, K., et al., Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med, 2019. 380(13): p. 1235-1246.
  2. Hussain, M., et al., Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med, 2018. 378(26): p. 2465-2474.
  3. Smith, M.R., et al., Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. N Engl J Med, 2018. 378(15): p. 1408-1418.
  4. Hofman, M.S. and A. Iravani, Gallium-68 Prostate-Specific Membrane Antigen PET Imaging. PET Clin, 2017. 12(2): p. 219-234.
  5. Perera, M., et al., Sensitivity, Specificity, and Predictors of Positive (68)Ga-Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer: A Systematic Review and Meta-analysis. Eur Urol, 2016. 70(6): p. 926-937.

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