A 75 years-old metastatic castration-resistant prostate cancer(mCRPC), Gleason score = 4 + 4, initial pTNM = T_3bN₁M₀,was referred to our center for PSMA-targeted radioligand therapy (PRLT).The patient previously received docetaxel, followed by enzalutamide and showed evidence of both biochemical and radiographic progression on these agents. His ⁶⁸Ga-PSMA-11 PET/CT before PRLT showed multiple bone and lymph nodes metastasis with intense PSMA avidity while the PSA levels were 7.62ng/ml at the time of imaging. This finding was not surprising since PSA and PSMA uptake have moderate to strong association [1]. In 2018, the patient received 4 cycles of ¹⁷⁷Lu-PSMA every 8 weeks with cumulative activity of 24.7 GBq and the PSA levels declined to 0.08 ng/ml with significant resolution of the disease burden Figure (a, b). The patient had debilitating bone pain prior to PRLT but after the first cycle of therapy the pain subsided dramatically. Transient grade Ianemia, lymphopenia and nephrotoxicity occurred during the course of PRLT. However, no severe adverse events were observed which is consistent with previous safety studies in this regard [2,3]. After finishing the 4 cycles of PRLT a near complete response was noted and the patient maintained on enzalutamide, considering the possible usefulness of this combination. Moreover, the patient had a history of long term diabetes mellitus and in a four years’ follow-up no long term nephrotoxicity and hematotoxicity was noted. The PSA levelsremainedbelow 0.1 ng/mland the patient is still alive with good quality of life and no skeletal pain. The patient showed near complete response and maintained on enzalutamide for 54 months after RLT without a need for further rechallenge RLT. In 2019 and 2021 two surveillance ⁶⁸Ga-PSMA PET/CTs were performed,revealing only a small focus of PSMA-avid metastasis in the posterior element of the 3^rd lumbar vertebra (SUV_max= 6.3)in the last follow up Figure (c). Previous cases with exceptional responses usually have had a relapsing course and repeated cycles of PRLT were warranted which is in contrast to our case [4]. This case illustrates an exceptional responder to PRLTwith durable response. To our knowledge, the biologically-derived markers for such phenomenon has not yet defined.