Impressive response to <sup>177</sup>Lu-PSMA-617 therapy in a patient with metastatic castration-resistant prostate cancer refractory to apalutamide, docetaxel and metastasis-directed therapy

PSMA-targeted radionuclide therapy (PSMA – prostate-specific membrane antigen) based on the theranostic concept of “treat what we see and see what we treat” has proven to be a highly effective therapeutic modality for metastatic castration-resistant prostate cancer (mCRPC). We present an illustrative case of the effectiveness and prospects of this therapy in mCRPC. The patient aged 84 years underwent external beam radiation therapy (EBRT) to the prostate area, seminal vesicles, and regional lymph nodes at the stage of locally advanced prostate cancer (cT3aN1M0, stage IV). After 28 months of androgen deprivation therapy, castration-resistant stage of the disease was registered with multiple metastases in the bones and pelvic lymph nodes. In combination with ongoing androgen deprivation therapy, the following treatments were sequentially performed: metastasis-directed therapy through stereotactic radiotherapy to the bone lesions, apalutamide in combination with stereotactic radiotherapy to the bone and lymph node lesions, and 5 courses of docetaxel chemotherapy. Time to progression with these therapies did not exceed 6 months. From December 2022 to May 2023, 177Lu-PSMA-617 PSMA-targeted therapy was performed (4 courses with an interval of 6–8 weeks, average therapeutic activity 7.6 GBq). Treatment was suspended due to development of complete radiologic response and the absence of metabolic substrate for continuation of therapy as well as total prostate-specific antigen decrease from 17 ng/mL (December of 2022) to 0.01 ng/mL (June of 2023). Among the adverse effects, the development of grade 1 xerostomia was noted. At the follow-up examination in March 2024, ECOG (Eastern Cooperative Oncology Group) score was 0, total prostate-specific antigen level was 0.05 ng/mL, complete radiologic response according to positron emission tomography/computed tomography with 18F-PSMA-1007 was registered, time without progression was 15 months. Therefore, PSMA-targeted radioligand therapy with 177Lu-PSMA-617 was highly effective with low toxicity in an elderly patient with mCRPC refractory to standard drug therapy.