The Prostate Cancer Clinical Trials Working Group (PCWG) is developing new criteria for evaluating prostate cancer progression using PSMA PET-CT scans, potentially replacing the current PCWG3 guidelines that rely on CT and bone scans. Data from the PRINCE trial suggests the new criteria can detect progression earlier and with better inter-reader agreement. This initiative aims to standardize response evaluation, improve patient experience, and enhance tumor assessment accuracy.
Development of PSMA PET-CT Criteria
Michael Hofman and the PCWG have been working on establishing standardized criteria for PSMA PET-CT to define progression and response in prostate cancer. The current PCWG guidelines use CT scans and bone scans, which have limitations, including lengthy procedures and nonspecificity. PSMA PET-CT offers a faster, more reliable alternative by imaging the tumor directly. The goal is to create criteria that are simple and visual, allowing any imaging specialist to determine progression or response consistently.
PRINCE Trial Data
The PRINCE trial, which investigated Lutetium PSMA-617 combined with Pembrolizumab, provided the data set for this initial evaluation. In this trial, PSMA PET-CT scans were collected alongside regular CT and bone scans but did not influence patient management. This setup allowed for a comparison between the new criteria and the existing PCWG3 guidelines.
The new criteria focus on the appearance of new lesions or the disappearance of existing lesions, similar to PCWG3. However, unlike PCWG3, the PSMA PET-CT criteria include a response category, enabling the identification of complete responses when all lesions disappear. The criteria do not consider changes in intensity or SUV values for determining progression or response.
Inter-Reader Agreement and Correlation with Overall Survival
In the PRINCE trial, involving 36 patients and 142 paired scans, the inter-reader agreement for the new criteria was substantial, with a kappa of 0.7 when considering all categories (complete response, partial response, stable disease, progression) and almost perfect (kappa of 0.9) when considering only progression versus no progression. This high level of agreement indicates that PSMA PET-CT scans can be interpreted reproducibly.
The PSMA PET-CT criteria detected progression earlier than PCWG3, and both sets of criteria correlated with overall survival. The correlation was slightly tighter for PSMA PET-CT, although this difference was not statistically significant due to the small sample size. These preliminary results suggest that PSMA PET-CT performs at least as well as, and potentially better than, PCWG3 in assessing prostate cancer progression.
Future Directions and Validation
Despite the promising results, concerns remain about the increased sensitivity of PSMA PET-CT and the potential for overtreatment. The PCWG is continuing to refine the criteria to address these concerns. Further validation is planned using data from multiple clinical trials to ensure the criteria are robust and correlate with overall survival.
The FDA has advised combining data from several trials to create a larger data set for validation. This approach mirrors the validation process used for bone scanning criteria. The ultimate goal is to replace bone scans with PSMA PET-CT, providing a one-stop shop for assessing prostate cancer progression. It is crucial to include contrast-enhanced CT as part of the PSMA PET-CT protocol to detect PSMA-negative lesions, such as liver metastases.
Michael Hofman emphasized that while the agreement for PSMA PET-CT is very good and the new criteria detect progression earlier, the real work lies in validating these criteria with larger data sets to ensure their reliability and clinical utility.
