Combined PRLT using Ac-225 and Lu-177 labeled PSMA-617 (TANDEM-PRLT) in end-stage metastatic prostate cancer: a concept to reduce salivary gland toxicity?

Ziel/Aim:

First clinical data using Ac-225- PSMA in metastatic prostate cancer (PC) demonstrated encouraging results. However, xerostomia became the dose-limiting toxicity. Recently, our group presented initial experience of a protocol of lower administered activity of Ac-225-PSMA-617 applied with Lu-177-PSMA-617 to minimize adverse effects while proposing synergistic efficacy. This study investigates salivary gland (SG) toxicity of that TANDEM approach.

Methodik/Methods:

Out of 30 end-stage PC patients selected for TANDEM-PRLT, 14 cases (median age 68 y) with available follow-up data at 2 months after treatment were examined. Risk factors like previous taxane-based chemotherapy (6 of 14 pts) or Lu-177-PSMA (10 of 14 pts) were considered. 2.0 – 7.0 MBq of Ac-225 and 3.0 – 7.2 GBq of Lu-177 were applied. Dryness of mouth was documented pre- and post-therapeutically according to CTCAE (v5.0) and the shorted xerostomia inventory (XI). Furthermore, a quantified salivary gland scintigraphy (SGS; maximum Uptake Umax; Ejection fraction EF) and SUV of the SG on the Ga-68-PSMA-11-PET/CT were compared.

Ergebnisse/Results:

Xerostomia increased significantly from grade 0 (max grade 1) to grade 1 (max grade 2; p = 0.006), the average XI rose from 10.73 (± 3.5) to 15.55 (± 4.18) (p = 0.003), however, no severe xerostomia was observed, no patient discontinued treatment. SGS revealed a significant decline of the EF in all SG (p < 0.01) while the Umax showed no significant changes. Despite tendencies, no significant changes of the Ga-68-PSMA uptake could be observed. Pretreatment with chemotherapy appeared to be a risk factor, although there was no significant correlation also with age.

Schlussfolgerungen/Conclusions:

Besides limitations (number of patients, early follow-up setting) initial results propose a reduced SG toxicity of the TANDEM-protocol. Nevertheless, since findings confirmed a clear SG impairment when using Ac-225-PSMA, preventive strategies remain an urgent need, especially in subsequent alpha-PRLT cycles.