Nomogram to predict the presence of PSMA-negative but FDG-positive lesion in castration-resistant prostate cancer: a multicenter cohort study
Jian Pan, Tingwei Zhang, Shouzhen Chen, Ting Bu, Jinou Zhao, Xudong Ni, Benkang Shi, Hualei Gan, Wei Yu, Qifeng Wang, Beihe Wang, Junlong Wu, Shaoli Song, Feng Wang, Chang Liu, Dingwei Ye, Yao Zhu
Abstract
Background: PSMA-negative but FDG-positive (PSMA−/FDG+) lesion in dual-tracer ( 68 Ga-PSMA and 18 F-FDG) positron emission tomography/computed tomography (PET/CT) is associated with an unfavorable response to Lutetium-177 ( 177 Lu)-PSMA-617. This study sought to develop both radiomics and clinical models for the precise prediction of the presence of PSMA−/FDG+ lesions in patients with castration-resistant prostate cancer (CPRC). Methods: A cohort of 298 patients who underwent dual-tracer PET/CT with a less than 5-day interval was included. The evaluation of the prognostic performance of the radiomics model drew upon the survival data derived from 40 patients with CRPC treated with 177 Lu-PSMA-617 in an external cohort. Two endpoints were evaluated: (a) prostate-specific antigen (PSA) response rate, defined as a reduction exceeding 50% from baseline and (b) overall survival (OS), measured from the initiation of 177 Lu-PSMA-617 to death from any cause. Results: PSMA−/FDG+ lesions were identified in 56 (18.8%) CRPC patients. Both radiomics (area under the curve [AUC], 0.83) and clinical models (AUC, 0.78) demonstrated robust performance in PSMA−/FDG+ lesion prediction. Decision curve analysis revealed that the radiomics model yielded a net benefit over the ‘screen all’ strategy at a threshold probability of ⩾4%. At a 5% probability threshold, the radiomics model facilitated a 21% reduction in 18 F-FDG PET/CT scans while only missing 2% of PSMA−/FDG+ cases. Patients with a low estimated score exhibited significantly prolonged OS (hazard ratio = 0.49, p = 0.029) and a higher PSA response rate (75% versus 35%, p = 0.011) compared to those with a high estimated score. Conclusion: This study successfully developed two models with accurate estimations of the risk associated with PSMA−/FDG+ lesions in CRPC patients. These models held potential utility in aiding the selection of candidates for 177 Lu-PSMA-617 treatment and guiding 68 Ga-PSMA PET/CT-directed radiotherapy.