Efficacy, nephrotoxicity and hematotoxicity after lu-177 PSMA treatment of metastatic castration resistant prostate cancer

Efficacy, Nephrotoxicity and Hematotoxicity After Lu-177 PSMA Treatment of Metastatic Castration Resistant Prostate Cancer Ogün BÜLBÜL, Dokuz Eylül University, Faculty of Medicine, Department of Nuclear Medicine Aim: To evaluate the effectiveness of Lu-177 PSMA treatment using PSA values and Ga-68 PSMA PET/CT, to determine the factors affecting overall survival and progression-free survival times, to determine nephrotoxicity and hematotoxicity of Lu- 177 PSMA treatment in patient diagnosed metastatic castration-resistant prostate cancer. Method: Fifty six patients undergoing Lu-177 PSMA treatment between 13.10.2015 - 19.10.2018 were identified. Before and after treatment of 48 patients with control blood values, serum PSA, LDH, ALP, BUN, Cr, eGFR values, hemogram parameters, Ga-68 PSMA PET/CT images of 21 patients had control PET/CT imaging were examined. Treatment response was evaluated according to Prostate Cancer Working Group-3 (PCWG-3) and Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST). Then treatment response evaluation results according to PSA and Ga-68 PSMA PET/CT were compared for 21 patients. Overall survival and progression-free survival times of patients were calculated and the factors affecting these times were determined. Post-treatment nephrotoxicity and hematotoxicity conditions were evaluated according to Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0). Results: In 33,3% of patients, a decrease of 50% or more in PSA compared to pretreatment, in 24,4% of patients decrease not more than 50% or increase not more than 25% in PSA, and in 42,3% of patients more than 25% increase in PSA was observed. In 52% of patients, any level of PSA decreased. When the posttreatment PSA decrease 50% or more was accepted as the goldstandart for treatment response 5 of 21 patinets underwent control Ga-68 PSMA PET/CT after treatment, the sensitivity of Ga-68 PSMA PET/CT in determining treatment response calculated as 75%, specifity was 77,8%, positive predictive value was 81,8% and negative predictive value was 70%. When the posttreatment PSA increase 25% or more was evaluated as goldstandard for disease progression of 21 patinets underwent control Ga-68 PSMA PET/CT after treatment, both sensitivity and specifity of Ga-68 PSMA PET/CT in determining disease progression calculated as 71,4, positive predictive value was 55,6%, negative predictive value was 83,3%. Mean overall survival of patients with 50% or more decrease after first cyclus was 21,8 ± 2,1 months, mean progression-free survival was 11,7 ± 1,4 months. These survival times were shorter for patinets without 50% or more decrease after first cyclus (13,7 ± 2,5 months, 5,6 ± 0,7 months, p values 0,025 and 0,001 respectively). Mean overall survival of patients with any decrease of PSA after first cyclus was 19,1 ± 1,9 months, mean progression-free survival was 10,6 ± 1,0 months. These survival times were shorter for patinets without any decrease of PSA first cyclus (13,8 ± 3,4 months, 4,0 ± 0,6 months, p values 0,048 ve 0,000 respectively). In patients with normal pre-treatment ALP levels, mean overal and progression-free survival (23,7 ± 3,2 months, 9,8 ± 1,3 months) was longer than patients with high ALP levels than 120 IU/L (11,7 ± 1,8 months, 5,8 ± 0,8 months, p values 0,008 ve 0,009 respectively). Overall survival times were found to be longer in patients with normal hemoglobin values before treatment than patients with low hemoglobin values (32,7 ± 4,5 months - 13,8 ± 1,6 months, p value: 0,011). As a result of Cox regression analysis, low hemoglobin before treatment was found to be an independent risk factor for lower total survival (hazard ratio: 4,810, 95% confidence interval 1,080-21,428, p value: 0,039). In 12,8% of patients, there was a first or second degree increase in creatinine and in 13,3% of patients, there was a first or second degree decrease in eGFR. There was no acute nephrotoxicity. No third or fourth degree nephrotoxicity was observed during the follow-up period. After treatment, 33,6% of patients had first or second degree hemoglobin decrease compared to baseline, and 2,1% of patients had third degree hemoglobin decrease. While 10,5% of patients had first or second degree leukopenia, third or fourth degree leukopenia was not observed. First degree thrompocytopenia was detected in 6,3% of the patients and fourth degree thrombocytopenia in 2,1% of the patients. 6 Conclusion: As a result of our study, it was found that patients with a decrease in PSA level after the first cycle Lu-177 PSMA treatment reached longer survival times, and it was concluded that radionuclide therapy would be successful in this patient group. In patients with 25% or more PSA increase after the first cycle, survival times were shorter and radionuclide treatment resulted in high rate of treatment failure in this patient group. However, temporary PSA elevation because of "flare phenomenon" can be observed in this patient group, albeit at a low rate. The nephrotoxicity and hematotoxicity profile of Lu-177 PSMA treatment was found to be reliable, similar to many studies in the literature. Key Words: Lu-177 PSMA, efficacy, overall survival, progression-free survival, nephrotoxicity, hematotoxicity, Ga-68 PSMA PET/CT.