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.

Thisapproach would address a frequently observed paradoxical response to treatmentwhereby radiographic disease progression occurs despite stable or declining PSAlevels, according to investigators.

Ina 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 progressionas determined by serial imaging with C-11 choline positron emissiontomography/computed tomography (PET/CT) despite having stable or declining PSAlevels.

JamalAlamiri, MB, BCh, of Mayo Clinic in Rochester, Minnesota, and colleaguesdefined radiographic progression of disease by an increase in blood poolcorrected maximum standardized uptake value of the index lesion on C-11 cholinePET/CT scans. Patients underwent serial PSA testing and C-11 choline PET/CTscans every 3 to 6 months. They confirmed suspicious lesions using conventionalimaging, subsequent C-11 choline PET/CT evaluation, or by biopsy of themetastatic lesions whenever feasible.

Ofthe 123 men, 43% had radiographic disease progression while on abiraterone orenzalutamide, Dr Alamiris team reported. At the time of radiographicprogression, 60.4% of patients demonstrated a parallel rise in PSA levels(group A), whereas 39.6% had stable or declining PSA levels (group B).

Themedian PSA level at the time of radiographic progression was significantlyhigher for group A than group B (3.1 vs 1.3 ng/mL). Bone-predominanceprogression occurred more frequently in group B than group A (90% vs 65%). Themedian time until radiographic progression was significantly longer for group Athan group B (9.5 vs 3.9 months).

The study revealed the presence of 5or more metastatic lesions, bone metastatic lesions, and local or prostatic beddisease predicted a paradoxical response, Dr Alamiri told Renal & Urology News. Patients on enzalutamide were 4.6 timesmore likely to have a paradoxical response compared with those on abiraterone. Onmultivariable analysis, however, only local or prostatic bed disease remained asignificant predictor of paradoxical response.

As for why radiographic progressioncan occur despite stable or declining PSA levels, Dr Alamiri said itis possible prostate cancer cells gaintreatment-induced androgen-receptor (AR)-independent resistance mechanisms dueto exposure to multiple therapies. Invitro studies of cell lines have found AR-indifferent mCRPC cells that donot depend onAR pathways for growth. These cell lines showed resistanceagainst second-generation hormone therapies such as abiraterone andenzalultamide and expressed cross-resistance against taxane-based chemotherapy.It is unknown whether the genetic and molecular findings reported in thesestudies explain the paradoxical response described in our study, Dr Alamirisaid. Future studies performing genomic analysis on biopsy samples frommetastatic site from these patients are needed to see if they will mimic themolecular resistance mechanisms described in the in vitro studies.

Reference

Alamiri J, Ahmed ME, Andrews JR, etal. Radiographic paradoxical response in patients with metastatic castration-resistantprostate cancer (mCRPC) undergoing treatment with second-generation hormonetherapy (second-HT). Presented at the 2020 American Society of ClinicalOncology Virtual Scientific Program held May 29 to 31. Abstract 5577.

https://meetinglibrary.asco.org/record/188050/abstract

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PET/CT Imaging Potentially Useful in Evaluating mCRPC Treatment Response - Renal and Urology News

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