Objective To explore the value of ⁶⁸Ga-PSMA PET/CT in efficacy evaluation and prognosis analysis in patients with metastatic castration-resistant prostate cancer (mCRPC) who accepted ¹⁷⁷Lu-EB-PSMA RLT.

Methods A retrospective analysis was conducted on data from 38 mCRPC age 68 (51, 75) patients who received ¹⁷⁷Lu-EB-PSMA therapy at Peking Union Medical College Hospital from January 2019 to December 2021, with follow-up data until December 31, 2022. We explored the correlation and predictive value of ⁶⁸Ga-PSMA PET/CT parameters with prostate-specific antigen (PSA) response, radiographic response, PSA progression-free survival (PSA-PFS), and overall survival (OS). Pearson correlation analysis was used to assess associations between variables. Prognostic factors were identified using logistic regression and Cox proportional hazards regression. Variables with P<0.2 in univariate analysis were included in multivariate analysis to determine independent predictors. Kaplan-Meier curves depicted PSA-PFS and OS over time, and stratified survival estimates for significant ⁶⁸Ga-PSMA PET/CT parameters were performed using the log-rank test.

Results Among the 38 mCRPC patients, 30 and 16 patients received 2 and 3 cycles of ¹⁷⁷Lu-EB-PSMA RLT, respectively. A PSA decline≥50% from baseline was observed in 57.9% (22/38) of patients. Kaplan-Meier analysis revealed median PSA-PFS of 4.8 months (95%CI: 2.7–6.7) and median OS of 11.9 months (95%CI: 8.0–17.3). Pearson correlation showed a moderate correlation between baseline total lesion PSMA (TLP) and baseline PSA (r=0.566, P=0.001), and a strong correlation between the change in TLP (ΔTLP) and change in PSA (ΔPSA) (r=0.722, P<0.001). Univariate logistic regression identified whole-body PSMA mean standardized uptake value (SUV_mean) (OR=2.005, 95%CI: 1.124–3.713; P=0.007) and baseline TLP (OR=1.100, 95%CI: 1.004–1.118; P=0.012) as predictors of best PSA response. Multivariate analysis confirmed whole-body SUV_mean as an independent predictor of best PSA response (OR=1.910, 95%CI: 1.009–3.799; P=0.030). Cox regression identified baseline PSMA-positive tumor volume (PSMA-VOL) (HR=0.799, 95%CI: 0.691–0.924; P=0.002) and baseline alkaline phosphatase (HR=0.919, 95%CI: 0.795–1.242; P=0.045) as independent predictors for PSA-PFS. Baseline PSA (HR=0.953, 95%CI: 0.920–0.987; P=0.007) and baseline PSMA-VOL (HR=0.810, 95%CI: 0.690–0.989; P=0.035) were independent predictors for OS. Kaplan-Meier curves demonstrated significantly prolonged PSA-PFS in patients with PSMA-VOL≤388 mL (6.2 vs. 2.9 months, P=0.013) and significantly prolonged OS in those with PSMA-VOL≤23 mL (15.3 vs. 7.5 months, P=0.001).

Conclusion The relevant parameters of ⁶⁸Ga-PSMA PET/CT have significant value for predicting the therapeutic efficacy and survival outcomes in patients with mCRPC undergoing ¹⁷⁷Lu-EB-PSMA RLT.