Prognostic Value of Baseline PSMA-PET Parameters in Metastatic Castration-Resistant Prostate Cancer

Strategic Insights -

A recent substudy of the ENZA-p trial has evaluated the prognostic value of baseline PSMA-PET parameters in patients with metastatic castration-resistant prostate cancer. The research, led by St Vincent's Hospital, has found that quantitative parameters derived from gallium-68 [Ga]Ga-prostate-specific membrane antigen (PSMA)-11 PET-CT, such as whole-body standardised uptake value (SUV)mean and total tumour volume (PSMA-TTV), have shown prognostic value for response to lutetium-177 [Lu]Lu-PSMA-617 monotherapy. The study also found that adding [Lu]Lu-PSMA-617 to enzalutamide improved overall survival compared with enzalutamide alone in patients with metastatic castration-resistant prostate cancer.

Key Takeaways:

  • The ENZA-p trial was an open-label, randomised, phase 2 trial conducted in 15 hospitals in Australia, involving 162 participants with progressive metastatic castration-resistant prostate cancer.
  • The study evaluated the prognostic value of baseline PSMA-PET parameters, including total tumour volume (PSMA-TTV) and SUVmean, in predicting response to lutetium-177 [Lu]Lu-PSMA-617 monotherapy.
  • The results showed that patients with baseline PSMA-TTV below the median had a median overall survival of 39 months, compared to 20 months for those with PSMA-TTV above the median (HR 0.23, 95% CI 0.13-0.42, log-rank p<0.0001).
  • The study also found that adding [Lu]Lu-PSMA-617 to enzalutamide improved overall survival compared with enzalutamide alone in patients with metastatic castration-resistant prostate cancer.
  • The Prostate Cancer Research Alliance initiative (Movember and Australian Federal Government), Prostate Cancer Foundation Challenge Award, St Vincent's Clinic Foundation, GenesisCare, RoyMorgan, Endocyte (a Novartis company), and Astellas supported this research.
  • The study has been peer-reviewed and published in the Lancet Oncology journal.

Statistics:

  • 162 participants were randomly assigned to either enzalutamide or enzalutamide plus [Lu]Lu-PSMA-617 between August 17, 2020, and July 26, 2022.
  • 160 patients received study treatment, with a median follow-up of 34 months (IQR 29-39).
  • 96 overall survival events were observed, with 53 events in the enzalutamide group and 43 events in the enzalutamide plus [Lu]Lu-PSMA-617 group.
  • The median SUVmean was 7.7 (IQR 6.5-9.8) and the median PSMA-TTV was 234 mL (76-687).
  • The study found that patients with baseline PSMA-TTV below the median had a median overall survival of 39 months, compared to 20 months for those with PSMA-TTV above the median.

Sources:

  • Prognostic and predictive value of baseline PSMA-PET total tumour volume and SUVmean in metastatic castration-resistant prostate cancer in ENZA-p (ANZUP1901): a substudy from a multicentre, open-label, randomised, phase 2 trial. Lancet Oncology, 2025.
  • NewsRx. Researchers at St Vincent's Hospital Report New Data on Prostate Cancer [Prognostic and predictive value of baseline PSMA-PET total tumour volume and SUVmean in metastatic castration-resistant prostate cancer in ENZA-p (ANZUP1901): a substudy ...]. Health & Medicine Week. August 22, 2025; p 6037.