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The Prognostic Role of 68GA-PSMA-PET/CT in Metastatic Hormone-Sensitive Prostate Cancer: A Preliminary Analysis - Beyond the Abstract

Prostate cancer (PCa) remains the most common malignancy and a leading cause of cancer-related death in men, especially in developed nations like the United States. With the treatment landscape for metastatic prostate cancer evolving rapidly — particularly in metastatic hormone-sensitive prostate cancer (mHSPC) — new imaging tools are playing an increasingly critical role in patient stratification and treatment personalization.

Historically, treatment decisions in mHSPC have relied on conventional imaging (CT, MRI, bone scans) and biochemical markers such as PSA. While PSA is a simple and widely used tool for disease monitoring, it has well-documented limitations, particularly in neuroendocrine variants or visceral metastases, where PSA expression may be minimal or non-existent.

68Ga-PSMA-PET/CT, a relatively novel imaging modality that targets prostate-specific membrane antigen (PSMA), offers higher sensitivity and specificity than traditional imaging. While it has already proven effective in the staging of high-risk and biochemically recurrent PCa, its potential prognostic role in mHSPC has remained under-explored. This study attempts to address that gap.

This is a retrospective, single-center, exploratory analysis aimed at evaluating the prognostic value of baseline 68Ga-PSMA-PET/CT parameters in patients with mHSPC undergoing systemic therapy.

Key features of the study:

  • Population: 32 mHSPC patients (both de novo and recurrent), staged with 68Ga-PSMA-PET/CT before starting treatment with either ADT + docetaxel ± darolutamide, or ADT + ARSI (apalutamide, enzalutamide, or abiraterone).
  • Endpoints:
    • Primary: Progression-free survival (PFS) associated with baseline PET parameters.
    • Secondary: Achievement of undetectable PSA during first-line treatment.
1. Baseline PSMA-PET/CT Parameters and PFS

  • Two imaging parameters — SUVmean and major SUVmax — were found to be significantly associated with longer PFS when their values were above specific cut-offs.
  • However, this correlation did not hold in univariate Cox analysis, possibly due to the small sample size and few progression events.
2. PET Parameters and Undetectable PSA

  • At both 3 and 6 months, lower values of certain PET metrics (e.g., TLA, SUVmean, MTV) were significantly associated with a greater likelihood of achieving undetectable PSA levels.
  • On multivariate analysis, MTV ≤ cut-off and SUVmean ≤ cut-off were independently associated with undetectable PSA at 3 months.
  • Additionally, low-volume disease (per CHAARTED criteria) was a strong independent predictor of reaching undetectable PSA.
3. Imaging-Response Paradox

A particularly interesting aspect of this study is the paradox between PFS and PSA response in relation to PET parameters:

  • Patients with higher PET uptake (SUVmax and SUVmean) at baseline had better PFS.
  • Conversely, those with lower PET uptake were more likely to achieve undetectable PSA.
This suggests a potential dissociation between biochemical and radiographic response, emphasizing the complexity of interpreting PSA kinetics and imaging features in tandem.

This study proposes a novel use for 68Ga-PSMA-PET/CT in predicting outcomes beyond its traditional diagnostic role. The potential ability to use baseline PET metrics to stratify prognosis or guide treatment intensity could mark a paradigm shift in managing mHSPC.

  • High SUVmean/SUVmax might reflect tumors that retain PSMA expression and androgen receptor signaling — features often linked to more indolent, treatment-sensitive disease.
  • On the other hand, low PET uptake could indicate a more biologically aggressive, dedifferentiated disease, less likely to respond to hormonal manipulation.
This aligns with prior findings (e.g., from the VISION trial) that patients with high whole-body SUVmean derived greater benefit from PSMA-targeted therapies.

Additionally, the correlation of low MTV and SUVmean with early PSA response supports the idea that baseline tumor burden and PSMA avidity might help predict depth and timing of PSA nadir, a known prognostic factor.

This preliminary retrospective analysis provides early but compelling evidence that 68Ga-PSMA-PET/CT has a potential prognostic role in mHSPC, with baseline PET metrics such as SUVmean, SUVmax, MTV, and TLA offering insights into both radiographic progression and PSA kinetics.

Despite inherent limitations, the findings suggest that PSMA-PET/CT may evolve from a diagnostic and staging tool into a prognostic biomarker, capable of informing treatment decisions and personalizing care in advanced prostate cancer.

Further prospective studies are warranted to validate these findings and define the most clinically relevant imaging metrics, potentially transforming the future standard of care in mHSPC.

Written by: Andrea Marchetti,1 Veronica Mollica,2 Andrea Farolfi,3 Gianfilippo Bianciardi,3 Matteo Rosellini,1 Elisa Tassinari,4 Linda Danielli,4 Lorenzo Bianchi,5 Riccardo Schiavina,5 Stefano Fanti,3 Francesco Massari4

  1. Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
  2. Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
  3. Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
  4. Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy; Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
  5. Division of Urology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Università degli studi di Bologna, Bologna, Italy.
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