Additive Value of [68Ga]Ga-RM26 PET/CT to [68Ga]Ga-PSMA-617 PET/CT in Detecting Pelvic Lymph Node Metastasis in Prostate Cancer: A Prospective, Single-Center, Phase II Study

Lymph node staging in prostate cancer is crucial for treatment and prognosis, yet [68Ga]Ga-PSMA-617 PET/CT has limited sensitivity in detecting pelvic lymph node metastasis (PLNM). [68Ga]Ga-RM26 PET/CT, targeting the gastrin-releasing peptide receptor, complements [68Ga]Ga-PSMA-617 PET/CT in assessing primary tumor extension and aggressiveness. However, its role in detecting PLNM and complementing [68Ga]Ga-PSMA-617 PET/CT remains underexplored. Methods: This prospective study enrolled newly diagnosed yet untreated prostate cancer patients who underwent [68Ga]Ga-RM26 PET/CT and [68Ga]Ga-PSMA-617 PET/CT, followed by radical prostatectomy and extended pelvic lymph node dissection. The primary objective was to evaluate the diagnostic performance of both PET/CT modalities in detecting PLNM. Results: In total, 68 patients were enrolled, with a 30.9% (21/68) pathologic PLNM rate. In patient-based analysis, [68Ga]Ga-RM26 PET/CT had sensitivity and specificity of 0.43 and 0.94, respectively, compared with 0.52 and 0.89 for [68Ga]Ga-PSMA-617 PET/CT. [68Ga]Ga-RM26 PET/CT detected additional PLNMs in 50% (5/10) of patients that were missed by [68Ga]Ga-PSMA-617 PET/CT. The combined use of [68Ga]Ga-RM26 PET/CT and [68Ga]Ga-PSMA-617 PET/CT resulted in sensitivity of 0.76 and specificity of 0.85. In total, 1,049 lymph nodes were dissected, including 991 normal and 58 positive nodes. In lesion-based analysis, [68Ga]Ga-RM26 PET/CT had sensitivity and specificity of 0.38 and 0.99, respectively, compared with 0.5 and 0.99 for [68Ga]Ga-PSMA-617 PET/CT. [68Ga]Ga-RM26 PET/CT identified 41.4% (12/29) of pathologic positive nodes missed by [68Ga]Ga-PSMA-617 PET/CT. The combined [68Ga]Ga-RM26 and [68Ga]Ga-PSMA-617 PET/CT demonstrated sensitivity of 0.71 and specificity of 0.99. Conclusion: In dual-target imaging, [68Ga]Ga-RM26 PET/CT identified additional PLNMs. The combination of [68Ga]Ga-RM26 PET/CT and [68Ga]Ga-PSMA-617 PET/CT achieved higher diagnostic sensitivity with minimal loss of specificity.