Metabolic imaging in conjunction with PSA testing could improve evaluation of treatment response and disease progression in men with metastatic castration-resistant prostate cancer (mCRPC), according to data presented during the American Society of Clinical Oncology 2020 Virtual Scientific Program.
This approach would address a frequently observed paradoxical response to treatment whereby radiographic disease progression occurs despite stable or declining PSA levels, according to investigators.
In a study of 123 men with mCRPC who received second-generation hormone therapy (either abiraterone or enzalutamide) post-taxane-based chemotherapy, investigators found that nearly 40% of men experienced radiographic progression as determined by serial imaging with C-11 choline positron emission tomography/computed tomography (PET/CT) despite having stable or declining PSA levels.
Jamal Alamiri, MB, BCh, of Mayo Clinic in Rochester, Minnesota, and colleagues defined radiographic progression of disease by an increase in blood pool corrected maximum standardized uptake value of the index lesion on C-11 choline PET/CT scans. Patients underwent serial PSA testing and C-11 choline PET/CT scans every 3 to 6 months. They confirmed suspicious lesions using conventional imaging, subsequent C-11 choline PET/CT evaluation, or by biopsy of the metastatic lesions whenever feasible.
Of the 123 men, 43% had radiographic disease progression while on abiraterone or enzalutamide, Dr Alamiri’s team reported. At the time of radiographic progression, 60.4% of patients demonstrated a parallel rise in PSA levels (group A), whereas 39.6% had stable or declining PSA levels (group B).
The median PSA level at the time of radiographic progression was significantly higher for group A than group B (3.1 vs 1.3 ng/mL). Bone-predominance progression occurred more frequently in group B than group A (90% vs 65%). The median time until radiographic progression was significantly longer for group A than group B (9.5 vs 3.9 months).
The study revealed the presence of 5 or more metastatic lesions, bone metastatic lesions, and local or prostatic bed disease predicted a paradoxical response, Dr Alamiri told Renal & Urology News. Patients on enzalutamide were 4.6 times more likely to have a paradoxical response compared with those on abiraterone. On multivariable analysis, however, only local or prostatic bed disease remained a significant predictor of paradoxical response.
As for why radiographic progression can occur despite stable or declining PSA levels, Dr Alamiri said it is possible prostate cancer cells gain treatment-induced androgen-receptor (AR)-independent resistance mechanisms due to exposure to multiple therapies. In vitro studies of cell lines have found “AR-indifferent” mCRPC cells that do not depend on AR pathways for growth. These cell lines showed resistance against second-generation hormone therapies such as abiraterone and enzalultamide and expressed cross-resistance against taxane-based chemotherapy. “It is unknown whether the genetic and molecular findings reported in these studies explain the paradoxical response described in our study,” Dr Alamiri said. Future studies performing genomic analysis on biopsy samples from metastatic site from these patients are needed to see if they will mimic the molecular resistance mechanisms described in the in vitro studies.
Alamiri J, Ahmed ME, Andrews JR, et al. Radiographic paradoxical response in patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing treatment with second-generation hormone therapy (second-HT). Presented at the 2020 American Society of Clinical Oncology Virtual Scientific Program held May 29 to 31. Abstract 5577.