Response measurement study in metastatic castration-resistant prostate cancer patients, treated with radium-223, to improve early response evaluation and understand the radium-223 induced immune response
- Conditions
- <p>Prostate cancer, castration resistant prostate cancer, mCRPC, radium-223, biomarker, immune response. Prostaatkanker, castratieresistente prostaatkanker, radium-223, biomarker, immuunrespons.</p>10038588
- Registration Number
- NL-OMON26890
- Lead Sponsor
- Bayer
- Brief Summary
CT and bone scintigraphy are not useful for response evaluation of bone metastases to 223Ra treatment in metastatic castration-resistant prostate cancer (mCRPC). PET using 68Ga prostate-specific membrane antigen 11 (68Ga-PSMA) is a promising tool for response evaluation of mCRPC. The aim of this study was to determine the utility of 68Ga-PSMA PET/CT for response evaluation of 223Ra treatment in patients with mCRPC. Methods: Within this prospective, multicenter, imaging discovery study, 28 patients with mCRPC, eligible for 223Ra treatment, were included between 2019 and 2022. Patients received 223Ra according to the standard of care. Study procedures included CT, bone scintigraphy, and 68Ga-PSMA PET/CT at baseline, after 3 and 6 cycles of 223Ra treatment, and on treatment failure. Response to 223Ra treatment was visually assessed on all 3 imaging modalities. Total tumor volume within bone (TTVbone) was determined on 68Ga-PSMA PET/CT. Intrapatient heterogeneity in response was studied using a newly developed image-registration tool for sequential images of PET/CT. Results were compared with failure-free survival (good responders vs. poor responders; cutoff, 24 wk) and alkaline phosphatase (ALP) response after 3 cycles. Results: Visual response assessment criteria could not distinguish good responders from poor responders on 68Ga-PSMA PET/CT and bone scintigraphy. For 68Ga-PSMA PET/CT, TTVbone at baseline was lower in good responders than in poor responders, whereas TTVbone increased in both groups during treatment. TTVbone was higher in patients with new extraosseous metastases during 223Ra treatment. Although TTVbone and ALP correlated at baseline, changes in TTVbone and ALP on treatment did not. 68Ga-PSMA response of TTVbone showed intrapatient heterogeneity in most patients. Conclusion: mCRPC patients with lower TTVbone on 68Ga-PSMA PET/CT have the best clinical outcome after 223Ra treatment. Response is highly heterogeneous in most patients. A decrease in ALP, which occurred in most patients, was not correlated with a decrease in TTVbone, which might make one question the value of ALP for disease monitoring during 223Ra treatment in clinical practice.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 28
• Age = 18 years
• Histologically confirmed, progressive prostate cancer during ADT. Castration-resistant disease is defined as a serum testosterone level of 50 ng per deciliter or lower (=1.7 nmol per liter) after bilateral orchiectomy or during maintenance treatment consisting of androgen-ablation therapy with a luteinizing hormone–releasing hormone agonist.
• Prior chemotherapy, other than docetaxel.
• Previous hemibody external radiotherapy or systemic radiotherapy with radioisotopes within the previous 24 weeks.
Study & Design
- Study Type
- Observational non invasive
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>1. Exploratory analysis of multiple biomarkers in relation to failure-free survival, defined as time to next line of treatment, best supportive care or death. Next line of treatment or best supportive care will be started upon clinical, biochemical and/or radiological signs of progression according to the PCWG3 criteria.<br /><br><br /><br>2. Exploratory analysis of the immune response during radium-223 treatment in relation to failure-free survival as defined above.</p><br>
- Secondary Outcome Measures
Name Time Method <p>1. Characterization of the mutational and immunological profile of pre-treatment tumor genome in relation to failure free survival as defined above.<br /><br><br /><br>2. Overall survival<br /><br><br /><br>3. Skeletal related events</p><br>