Initial Experience of Lung Metastases Response to 225Ac-PSMA-617 Therapy in Metastatic Prostate Adenocarcinoma

Introduction: Prostate adenocarcinoma (PCa) is a leading cause of morbidity and mortality in males. Recently Peptide radioligand radionuclide therapy (PRLT) with alpha-emitter ²²⁵Actinium (²²⁵Ac) prostate specific membrane antigen (PSMA) has been shown to prolong survival and improve quality of life in both heavily pre-treated metastatic castration resistant prostate cancer (mCRPC) and chemotherapy-naïve patients. Visceral metastases, including lung metastases in PCa have been associated with reduced overall survival compared to bone metastases. We aimed to report initial experience in the response of lung metastases treated with ²²⁵Ac-PSMA-617 radioligand therapy (RLT) in metastatic prostate cancer.

Methods: We retrospectively reviewed 8 patients with mCRPC and metastatic treatment-naïve PCa who presented for RLT with ²²⁵Ac-PSMA-617 and had lung metastases among other sites of extra-prostatic involvement. The patients received ²²⁵Ac-PSMA-617 8 weekly with initial activity of 8 MBq that was de-escalated based on response. Prostate specific antigen (PSA) was measured prior every therapy and followed up 3 monthly post completion of therapy. ⁶⁸Ga-PSMA PET/CT imaging was performed 8 weekly during therapy and 6 monthly post completion.

Results: All patients had widespread nodal, lung and skeletal metastases. One patient also had testicular metastasis. All patients had good functional status. Four patients had Eastern Cooperative Oncology Group (ECOG) score of 0, 3 had a score of 1 and 1 had a score of 2. Six patients had prior treatments with a combination of hormonal therapy, chemotherapy and radiotherapy. Two patients were chemotherapy-naïve. All patients received at least 3 cycles of RLT as planned with initial activity of 8 megabecquerels (MBq). Four patients had additional cycles due to persistent disease. All patients demonstrated decline in PSA. PSA was undetectable (<0.1ug/L) in 3 patients (38%) and had decline of > 90% in 6 patients (75%). All patients demonstrated some overall response to ²²⁵Ac-PSMA-617 on PET/CT with 50% achieving complete regression of all metastases. Lung metastases demonstrated complete regression in 7 patients (88%) after 2 cycles of therapy. Two patients with overall partial response and complete regression of lung metastases died within 8 weeks of therapy completion and one patient was lost to follow-up. The rest of the patients had a minimum follow-up of 12 (range 12-48) months and demonstrated no recurrence of lung metastases on ⁶⁸Ga-PSMA PET/CT imaging.

Conclusions: Good overall response was noted in this cohort with overall remission in half the patients and complete regression of lung metastases in 88% with no recurrence during follow-up (up to 48 months). Larger prospective studies will be invaluable in assessing long-term efficacy and survival benefit of ²²⁵Ac-PSMA-617 in patients with lung metastases.

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