Combination Metastasis-Targeted External Beam Radiation Therapy With 177Lu-PSMA-617 in Patients With Advanced Castration-Resistant Prostate Cancer.

Purpose: ¹⁷⁷Lu-PSMA-617 (LuPSMA) is an effective radiopharmaceutical therapy for patients with metastatic castration-resistant prostate cancer. While LuPSMA can treat disseminated disease, additional localized control of metastatic disease may be required. Metastasis-targeted external beam radiation therapy (M-EBRT) can be an effective adjunct. However, the indications, efficacy, and safety/toxicity of combining M-EBRT with LuPSMA are unclear. Here, we report our experience with M-EBRT in patients receiving LuPSMA and assess M-EBRT's ability for local disease control and palliation.

Methods and materials: This retrospective institutional review board-exempted study reviewed patients treated with LuPSMA at a multi-institutional academic cancer center within the first 2 years after United States Food and Drug Administration's approval, receiving contemporaneous M-EBRT. Clinical factors driving the use of M-EBRT were analyzed.

Results: Treatment courses of 261 patients receiving LuPSMA were reviewed; 52 patients received M-EBRT contemporaneously. M-EBRT was administered for intracranial/epidural disease (n = 22/52; 42%), bone pain palliation (n = 17/52; 33%), prevention of pathological fractures (n = 12/52; 23%), and 12% (n = 6/52) for various other indications. M-EBRT timing varied among patients, with 54% (n = 28/52) receiving M-EBRT before, 27% (n = 14/52) after, and 13% (n = 7/52) during LuPSMA therapy. EBRT was mostly well tolerated, although lymphopenia was commonly experienced. Most patients (n = 32/52; 62%) had symptom relief following M-EBRT. Symptom relief post-M-EBRT was 68%, 85%, and 50%, and mortality rates were 32%, 29%, and 57% for patients receiving EBRT before, during, and after LuPSMA treatment, respectively, albeit not statistically significant (P > .23). Prostate-specific antigen (PSA)50 (decrease in PSA by 50% during treatment) response in this patient population was 41% compared with 50% in the general LuPSMA population, but the magnitude of PSA response was heterogeneous (P = .27).

Conclusions: In our experience, M-EBRT was used effectively with LuPSMA therapy for local tumor control and symptom management, especially for localized osseous and central nervous system lesions, and with good tolerability. M-EBRT may be an important adjunct treatment modality that facilitates the initiation and/or continuation of LuPSMA.