Sue Ping Thang1, John Violet2, Shahneen Sandhu3, Amir Iravani4, Tim Akhurst5, Grace Kong5, Aravind Ravi Kumar5, Declan G Murphy6, Scott G Williams7, Rodney J Hicks5, Michael S Hofman8. 1. Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia; Department of Nuclear Medicine and Molecular Imaging, Singapore General Hospital, Singapore. 2. Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia. 3. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, Melbourne, Australia. 4. Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia. 5. Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, Melbourne, Australia. 6. Sir Peter MacCallum Department of Oncology, Melbourne, Australia; Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia. 7. Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, Melbourne, Australia. 8. Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, Melbourne, Australia. Electronic address: michael.hofman@petermac.org.
Abstract
BACKGROUND: Prostate-specific membrane antigen (PSMA) is overexpressed in metastatic castration-resistant prostate cancer (mCRPC) and represents a target for imaging and therapy. We undertook a prospective trial of 177Lu-PSMA-617 radioligand therapy in men with high PSMA expression who progressed after standard therapies. OBJECTIVE: To determine outcomes for men screened for the trial but not treated because of low PSMA expression. DESIGN, SETTING, AND PARTICIPANTS: Patients screened with 68Ga-PSMA-11 and 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography in a prospective trial. Patients ineligible for enrolment with low PSMA expression or FDG-positive PSMA-negative (discordant FDG-avid) disease were assessed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Subsequent treatments received were recorded. Kaplan-Meier analysis was used to determine overall survival from date of screening. RESULTS AND LIMITATIONS: Sixteen patients (24%) had low PSMA expression (n=8) or discordant FDG-avid disease (n=8). The median prostate-specific antigen doubling-time was 2.1mo. Eleven patients had Gleason ≥8 disease. All patients had previously progressed after docetaxel, 44% after cabazitaxel, and 94% after abiraterone and/or enzalutamide. Nine patients had subsequent systemic antitumour treatment. Fifteen patients died, with median OS of 2.5mo (95% confidence interval 1.7-5.0). Study limitations include uncertainty for imaging thresholds that define low PSMA expression. It is also possible that theranostic therapy could have improved survival in this cohort. CONCLUSIONS: Low PSMA expression or discordant FDG-avid disease in patients with mCRPC who progress after conventional therapies identifies a group with poor prognosis and short survival. PATIENT SUMMARY: The 177Lu-PSMA-617 radioligand may be an effective therapy for patients with advanced prostate cancer who progress after standard therapies. In this report we looked at outcomes for patients who were not eligible for this novel therapy on the basis of low prostate-specific membrane antigen uptake on screening positron emission tomography scans. We found that their outcomes were poor, with short survival.
BACKGROUND:Prostate-specific membrane antigen (PSMA) is overexpressed in metastatic castration-resistant prostate cancer (mCRPC) and represents a target for imaging and therapy. We undertook a prospective trial of 177Lu-PSMA-617 radioligand therapy in men with high PSMA expression who progressed after standard therapies. OBJECTIVE: To determine outcomes for men screened for the trial but not treated because of low PSMA expression. DESIGN, SETTING, AND PARTICIPANTS: Patients screened with 68Ga-PSMA-11 and 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography in a prospective trial. Patients ineligible for enrolment with low PSMA expression or FDG-positive PSMA-negative (discordant FDG-avid) disease were assessed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Subsequent treatments received were recorded. Kaplan-Meier analysis was used to determine overall survival from date of screening. RESULTS AND LIMITATIONS: Sixteen patients (24%) had low PSMA expression (n=8) or discordant FDG-avid disease (n=8). The median prostate-specific antigen doubling-time was 2.1mo. Eleven patients had Gleason ≥8 disease. All patients had previously progressed after docetaxel, 44% after cabazitaxel, and 94% after abiraterone and/or enzalutamide. Nine patients had subsequent systemic antitumour treatment. Fifteen patientsdied, with median OS of 2.5mo (95% confidence interval 1.7-5.0). Study limitations include uncertainty for imaging thresholds that define low PSMA expression. It is also possible that theranostic therapy could have improved survival in this cohort. CONCLUSIONS: Low PSMA expression or discordant FDG-avid disease in patients with mCRPC who progress after conventional therapies identifies a group with poor prognosis and short survival. PATIENT SUMMARY: The 177Lu-PSMA-617 radioligand may be an effective therapy for patients with advanced prostate cancer who progress after standard therapies. In this report we looked at outcomes for patients who were not eligible for this novel therapy on the basis of low prostate-specific membrane antigen uptake on screening positron emission tomography scans. We found that their outcomes were poor, with short survival.
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