Abstract :
[en] Monitoring treatment response in metastatic castration-resistant prostate cancer (mCRPC) remains a major challenge. Conventional strategies, based on PSA levels and standard imaging, often provide delayed or ambiguous information and fail to capture tumor heterogeneity, leading to late identification of non-responders and potentially worse outcomes. This thesis investigated [⁶⁸Ga]Ga-PSMA-11 PET/CT as a dynamic biomarker for early therapy response assessment in mCRPC patients initiating androgen receptor pathway inhibitors (ARPIs), with the aim of determining whether early imaging changes could predict long-term clinical outcomes.
Across three studies, we explored the feasibility, prognostic value, and biological interpretation of early sequential [⁶⁸Ga]Ga-PSMA-11 PET/CT. The first study showed that global tumor response at 4 weeks was strongly associated with the 12-week response, highlighting the potential of early imaging to detect early treatment resistance, while cautioning against misinterpretation due to a possible flare phenomenon. The second study showed that while this flare was relatively common, affecting about one in four patients, it was generally of low magnitude. The third study demonstrated that interlesional heterogeneity, with progression in only a subset of lesions despite global stability or favorable response, was associated with early treatment failure and poor survival, underscoring the prognostic and potentially predictive value of lesion-level assessment using [⁶⁸Ga]Ga-PSMA-11 PET/CT.
Overall, these findings support the clinical relevance of early imaging and interlesional heterogeneity analysis, warranting further investigation to refine the prediction of treatment efficacy and failure in mCRPC. This approach could identify high-risk patients overlooked by standard criteria, enabling earlier treatment adaptation and potentially improving outcomes. This work establishes the foundation for a more dynamic, personalized, and biologically informed model to mCRPC management.
