ASCO 2024: 68Ga-PSMA PET/CT Response and Clinical Outcomes in Patients Treated with Enzalutamide as First-Line Therapy for Metastatic Castration-Resistant Prostate Cancer: Results of a Prospective Study

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, IL between May 31st and June 4th, 2024 was host to a prostate, testicular, and penile cancers poster session. Dr. Emilio Giunta presented the results of a prospective study evaluating the association between 68Ga-PSMA PET/CT response and clinical outcomes in metastatic castrate-resistant prostate cancer (mCRPC) patients treated with first-line enzalutamide.


There has been a long-standing interest in evaluating 68Ga-PSMA PET/CT as a response assessment tool for mCRPC patients receiving systemic therapy. In this study, the investigators evaluated the impact of 68Ga-PSMA PET/CT response, as compared to prostate-specific antigen (PSA) response, in patients treated with enzalutamide as first-line therapy for mCRPC.

This was a prospective observational study of 70 consecutive mCRPC patients treated with 1st line enzalutamide 160 mg once daily and who underwent a 68Ga-PSMA PET/CT within three weeks before (baseline) and 12 weeks after (SD: ±4 weeks) treatment initiation, between October 2017 and May 2022.
The investigators assessed the following parameters at both time points:

  • Sum of metabolic total volume (sMTV)
  • Mean and maximum standardized uptake volume (sSUVmean and sSUVmax, respectively)
  • Total lesion activity, which is the product of MTV and SUVmean, for a maximum of 20 lesions

Using the EAU/EANM criteria, patients were categorized as PSMA responders (PET-R, in case of complete/partial response or stable disease) or PSMA non-responders (PET-NR, in case

of progressive disease). Based on the serum prostate-specific antigen (PSA) levels, patients were

classified as biochemical responders (PSA-R, in case of PSA decrease ≥ 50%) or non-responders

(PSA-NR in all other cases). Survival analyses were performed using the Cox regression hazard model and the Kaplan-Meier method.

At the data cut-off date of December 2023, 69 mCRPC patients were fully evaluable. The median follow-up was 57 months (range: 3–74). The baseline patient characteristics are summarized below. The median age was 75 years. The median baseline PSA level was 2.57 ng/ml. The most common site of PSMA-PET visible disease was lymph nodes (67%), followed by bone (54%) and prostate (36%).
68Ga-PSMA PET/CT clinical characteristics
The median progression-free survival (PFS) was 36.7 months (95% CI: 26.4–66.5), while the median overall survival (OS) was 66.5 months (95% CI: 38.3–not reached). A contingency table summarizing the concordance/discordance between PSA and PSMA PET responses after three months of starting enzalutamide is illustrated below.68Ga-PSMA PET/CT contigency table
Differences between the discordant groups (PSA-R/PET-NR and PSA-NR/PET-R) were not statistically significant for both median progression-free survival (mPFS) and median overall survival (mOS) (p=0.09 and 0.41, respectively), even if a positive trend for PSMA PET was shown (Table 2).image-3.jpg
On multivariable analysis, only total lesion activity at 12 weeks was significantly associated with both median PFS and median OS (Table 3).
68ga-psma-pet-ct multivariable analysis, only total lesion activity at 12 weeks was significantly associated with both median PFS and median OS
Dr. Giunta concluded as follows:

  • PSA monitoring is less informative than 68Ga-PSMA PET/CT response to predict progression-free survival in mCRPC patients receiving enzalutamide as first-line therapy.
  • Some PET parameters may better predict survival benefit but need future validation.

Presented by: Emilio Francesco Giunta, MD, Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.

Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, May 31st – June 4th, 2024