ASCO GU 2019: Randomized Phase III Trial of 68Ga-PSMA-11 PET/CT Molecular Imaging for Prostate Cancer Salvage Radiotherapy Planning

San Francisco, CA (  Salvage radiotherapy (SRT) for prostate cancer biochemical recurrence after radical prostatectomy (RP) is commonly administered to patients with PSA < 1 ng/mL, a threshold at which standard-of-care imaging is not sensitive enough to detect disease recurrence.  68Ga-PSMA-11 PET/CT (PSMA) PET/CT molecular imaging is highly sensitive for detecting regional and distant metastatic recurrent prostate cancer at low PSA levels. This lead to the assumption that PSMA can help guide and improve SRT.  

A recent multicenter retrospective study in 270 patients with early biochemical recurrence (PSA<1.0 ng/ml), following RP was conducted. The results demonstrated that PSMA PET/CT had a major impact in 19% of patients undergoing SRT by showing lesions outside the standard radiation field. Most frequent localization of out of field lesions was in the bone and the perirectal area. According to Dr. Calais,  this retrospective study justified conducting a randomized phase 3 imaging trial of SRT with or without PSMA PET/CT investigating its potential benefit on clinical outcome.

In this presented randomized phase 3 trial ,presented in a poster format, the defined goal was to evaluate the success rate of SRT for biochemical recurrence following RP with and without planning based on PSMA scan. In this poster, Dr. Calais presented the protocol of this randomized trial. According to the protocol, a total of 193 patients will be randomized to either a control arm (standard SRT, n=90) and an intervention arm (PSMA PET/CT prior SRT planning, n=103). The primary endpoint is the success rate of SRT measured as biochemical progression-free survival. The secondary endpoints include 5-year biochemical progression-free survival from initiation of SRT, metastasis-free survival, initiation of additional salvage therapy after completion of SRT, and change in initial treatment intent. Patients will be followed for five years, and the trial design is shown in figure 1.

Figure 1 – Trial design:
Randomized Phase III Trial of 68GaPSMA11 PETCT Molecular Imaging for Prostate Cancer Salvage Radiotherapy Planning

The choice of treating the prostate bed with or without treating the pelvic lymph nodes, and with or without androgen deprivation therapy, is left to the discretion of the treating radiation oncologist. According to the trial protocol, the treating radiation oncologist may or may not change the radiotherapy plan depending on the PSMA findings. Any other imaging is allowed for SRT planning if done per routine care.  

Lastly, the main issues and pitfalls of the study include: 
  1. Drop-out of patients randomized to the control arm
  2. Potential FDA approval of PSMA PET imaging probes in the near future (no randomization to standard arm would be then acceptable).  
This is the first prospective randomized phase 3 trial designed to determine whether PET/CT can improve the outcome of SRT in patients with biochemical recurrence, and we eagerly await its results. 

Presented by: Jeremie Calais, MD, MSc, Assistant Professor at the Ahmanson Translational Imaging Division of the Department of Molecular and Medical Pharmacology, UCLA Nuclear Medicine Department, Los Angeles, CA

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA

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