Clinical Variables Associated with PSA Response to Lutetium-177-PSMA ([177Lu]-PSMA-617) Radionuclide Treatment in Men with Metastatic Castration-Resistant Prostate Cancer

Lutetium-177-PSMA ([177Lu]-PSMA-617), a radiolabeled small molecule, binds with high affinity to prostate-specific membrane antigen (PSMA), enabling targeted radiation therapy to metastatic prostate lesions. Our objective was to retrospectively analyze the activity of [177Lu]-PSMA-617 given off-trial to men with metastatic castration resistant prostate cancer (mCRPC) and identify clinical factors associated with PSA response. Electronic medical records of all men treated with [177Lu]-PSMA-617 were reviewed and analyzed. Overall survival was calculated using the Kaplan–Meier method. The association between potential variables and PSA response was analyzed by univariate analysis, using either logistic regression or χ(2)/Fisher’s exact test. Multivariable analysis was carried out using logistic regression on all categorical variables with a P-value of <0.1 on univariate analysis. Variables found to be statistically significant were then used to define a categorical score. A total of 52 patients received at least one cycle of [177Lu]-PSMA-617. Clinical benefit was observed in 28 patients (52%). PSA decline ≥20% and ≥50% was observed in 26 (50%) and 18 patients (35%), respectively. Achievement of any PSA decline at first measurement was significantly associated with survival. There was a negative association between the number of previous chemotherapy lines and PSA decline above 20%. Univariate analysis followed by multivariable analysis showed that older age and higher hemoglobin were significantly associated with a PSA decline >20%. A score combining these two parameters was significantly associated with PSA response. In summary, [177Lu]-PSMA-617 is active in the ‘real-life’ setting of heavily pretreated men with mCRPC.