Applying Staging PSMA PET/CT in De Novo Metastatic Hormonal Sensitive Prostate Cancer (mHSPC): A Preliminary Single-Center Retrospective Review of Clinical Outcomes

Introduction: Several Phase III clinical trials have established that upfront treatment intensification with double or triple therapy combining androgen deprivation therapy, new androgen pathway inhibitors and chemotherapy have improves clinical outcome in De Novo metastatic hormonal sensitive prostate cancer (mHSPC), especially in patients with high-volume disease. However, many of these trials staged HSPC using conventional imaging modalities such as CT/MR and bone scan. PSMA PET/CT has improved the detection of regional and distant metastases compared to conventional imaging modalities. In this study, we applied staging PSMA PET/CT in categorizing high-volume, and low-volume mHSPC and correlated with their clinical outcomes.

Methods: We retrospectively reviewed staging PSMA PET/CT performed at our institution from November 2021 to September 2022. The PSMA PET/CT categorized patients into three groups: no metastatic disease (N0M0), metastatic pelvic lymph nodes only (N1M0), low-volume and high-volume metastatic disease (M1). High-volume disease was defined as presence of visceral metastases or ≥4 bone lesions with ≥1 beyond the vertebral bodies and pelvis based on the CHAARTED trial criteria. Overall survival (OS) and biochemical progression free survival (bPFS) for each group were determined. Kaplan-Meier survival analysis with the Log Rank test was performed to compare N1M0, low-volume, and high-volume M1 groups.

Results: Fifty HSPC patients (median age 71, range 57-90 year; median PSA 14.1, range 1.9-588.0 ng/mL) were found to have metastatic disease on staging PSMA PET/CT. Among them, 17 patients were staged as N1M0, 14 as high-volume and 19 as low-volume M1 disease. Patients were treated with standard of care based on patient tolerance and comorbidities. With a median follow up of 19 months, no patients in the N1M0 group progressed biochemically, and one patient died from a cause not directly related to prostate cancer and was excluded from the analysis. In the low-volume M1 group, 2 patients (11%) progressed biochemically, while no patient died. In the high-volume M1 group, 5 patients (36%) progressed biochemically (P = 0.009 vs. N1M0 group and P = 0.07 vs. low-volume M1 group) and 3 patients (21%) died (P = 0.04 vs. N1M0 group and P = 0.02 vs. low-volume M1 group).

Conclusions: High-volume M1 disease on staging PSMA PET/CT may be associated with poorer biochemical progression-free survival and overall survival despite upfront treatment intensification in De Novo mHSPC patients. A larger patient cohort and longer follow up are needed to confirm these findings.