Background: Lu177-PSMA-617 (LuPSMA) is a recently approved treatment for patients with metastatic castration resistant prostate cancer (mCRPC). Successful treatment in real-world practice requires coordination between nuclear medicine, radiation safety, and medical oncology. We report outcomes from implementation of a multidisciplinary approach for LuPSMA administration at our institution. Methods: Our practice prior to treatment included collaborative radiologist review of PSMA PET/CT and oncologist review of prior therapies, performance status, and baseline laboratory values to establish candidacy. For each administration, procedures included confirming IV patency, use of a shielded infusion pump, IV hydration, and standardized radiation safety recommendations. On treatment, practices included scheduled laboratory monitoring, standardized treatment holds and dose reductions, coordination of care with a dedicated advanced practitioner, and mid-treatment conventional imaging. Retrospective chart review was completed for 100 mCRPC patients who received ≥1 dose of LuPSMA from June 2022 to August 2023 under this protocol. Outcomes including number of treatments, dose reductions/holds, PSA, and clinical imaging responses were reviewed. Results: Ninety-eight patients were included in the analysis (2 patients were excluded due to prior LuPSMA on clinical trial). In patients completing LuPSMA at time of data collection, median number of treatments was 4.0 (IQR=4.0, n=95), with 41% receiving all 6 planned treatments (n=39/95). During treatment, 16% experienced a treatment hold (n=16/98) with 25% ultimately completing 6 treatments (n=4/16; median=3.0, IQR=3.25). Holds were due to worsening symptoms (44%, n=7/16) or cytotoxicity (44%, n=7/16). Dose reductions occurred in 8% (n=8/98), with 38% completing 6 treatments (n=3/8; median treatments= 4.5, IQR= 3.0). Early discontinuation primarily occurred due to clinician-assessed progression (57%, n=32/56) or cytotoxicity (25%, n=14/56). Of those with early discontinuation due to progression, 70% had a rising PSA at time of discontinuation (n=21/30) and all had worsening disease on available mid-treatment imaging (n=15/15). For the remainder with early discontinuation due to progression, 20% had stable PSA (n=6/30) and 10% had decreasing PSA at time of discontinuation (10%, n=3/60). In those with stable or rising PSA, 75% terminated treatment due to worsening disease on available mid-treatment imaging (n=6/8). Conclusions: Our protocol for LuPSMA administration allows for early identification of clinical progression and completion of therapy when appropriate. Treatment holds and dose reductions facilitate therapy completion in select patients. Mid-treatment imaging may identify worsening disease in the setting of stable or decreasing PSA, underlying the potential importance of this practice for clinical decision making.