Salivary gland toxicity after PRLT using Lu-177 PSMA in patients with advanced prostate cancer: A single-center systematic investigation

540 Objectives: During Lu-177 PSMA radioligand therapy (PRLT) of advanced prostate cancer (PC), an intense off-target uptake of the radiopharmaceuticals with considerable absorbed organ doses to the salivary glands (SG) is observed. The reported occurrence of mild to moderate xerostomia varies between 5-8 % (1,2) to up to 87 % of the cases (3), probably due to variance of treatment cohorts or methodological differences of data acquisition. Objective of this study was a systematic and long-term follow up investigation of a larger single-center population of advanced PC cases after PRLT using patient reported outcome measures as well as clinical examination and diagnostic procedures for a subjective and objective assessment and approximated quantification of salivary gland toxicity. Methods: Prospectively acquired data of 2 patient groups were analyzed, a detailed informed consent was given before study inclusion. In group A 91 patients with advanced PC (median Gleason score = 8; median age = 68 years, range 46-90) were included, undergoing 2 cycles of Lu-177 PSMA PRLT applying a median cumulative activity of 14.3 GBq (range 9.5 - 20.2 GBq). Before the first PRLT cycle baseline data were obtained, including an enoral clinical examination, a standardized questionnaire (xerostomia inventory; XI), a dynamic salivary gland scintigraphy (SGS) using Tc-99m pertechnetate with both qualitative and quantitative assessment (maximum uptake Umax; Ejection fraction EF after oral stimulus with lemon juice) as well as the SUV and the metabolic volume of the SGs in the pretherapeutic Ga-68 PSMA -PET/CT study. Furthermore, possible risk factors for xerostomia (pretreatments, medication) were considered. Follow up data of all mentioned parameters were acquired accordingly after 2 cycles. In a second group (B) 40 patients with advanced PC were analyzed, who received 2-9 cycles of PRLT (mean cumulative activity 35.3 GBq, range 9.9-61.8 GBq) up to 52 months after the first cycle. Follow-up data was obtained similar to group A (clinical examination, questionnaires, dynamic SGS and Ga-68 PSMA PET/CT uptake). Results: Group A: At baseline, 13 of 91 patients (14.3 %) reported occasional, mild xerostomia. That number increased significantly to 22 of 91 patients (24.2 %) after 2 cycles of PRLT (p= 0,007). However, mouth dryness did not exceed grade 1 (mild) according to common criteria (CTCAE v. 5.0). Pre- and post-therapeutic SGS revealed no significant changes both qualitatively and quantitatively. SUV of all SGs did not show any significant changes, however, there was a highly significant decline of the metabolic volume detectable (p< 0.001). Group B: 15 of 40 patients reported mild xerostomia, whereas 1 patient demonstrated moderate (grade 2) mouth dryness. SGS showed no significant changes of the Umax and EF to available baseline studies. While the pre- and post-therapeutic SUV in the Ga-68 PSMA PET/CT revealed no significant differences, the metabolic volume of the SGs demonstrated a highly significant decline as well. Conclusions: SG toxicity after Lu-177 PSMA appears to have clinical minor relevance compared to experience from EBRT in patients with head and neck malignancies or recent results of PRLT with Ac-225 PSMA (4-6). However, mild to moderate xerostomia was reported in 24-40 % of the analyzed patient cohorts. As previously published (7) the volume of the SGs demonstrates a significant decline, especially after repetitive cycles of Lu-177 PSMA in a long-term setting. In contrast, dynamic SGS supports a preserved function of the SG in the vast majority of the patients. Therefore, more long-term follow up data as well as preventive approaches are a clinical eminently unmet need.