Intensified RLT Boosts Treatment Efficacy in Patients With mCRPC

Patients with metastatic castration-resistant prostate cancer (mCRPC) who undergo radioligand therapy (RLT) often receive a standard treatment of up to 6 cycles of 6.0-7.4 GBq ¹⁷⁷Lu-PSMA-617 or ¹⁷⁷Lu-PSMA-I&T.

While administering RLT using this standard protocol is deemed safe and effective, patients with higher tumor load may benefit more from dose escalation approaches if higher off-target radiation to critical organs can be avoided.

At the 2024 Society of Nuclear Medicine and Molecular Imaging Annual Meeting, Nicolai Mader, MD, presented results of a study that investigated an intensified treatment protocol using increased administered activities of >10 GBq ¹⁷⁷Lu-PSMA-I&T per cycle during the initial treatment phase, making use of the tumor sink effect.

A total of 49 patients with high-volume tumor burden at baseline were administered 10.5 ± 0.4 GBq per cycle every 6 to 8 weeks for 3 of 6 intended cycles, followed by standard activities in responding patients who were assessed by ⁶⁸Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT).

A significant prostate-specific antigen decline of 73% ± 31% was seen in 36 (73%) patients after 3 dose-escalated cycles. ⁶⁸Ga-PSMA-11 PET/CT detected partial response in 32 (65%) patients, stable disease in 5 (10%), and progressive disease in 12 (25%).

Grade 3 hematological toxicities in any blood parameter occurred in 3 (6%) patients. No grade 4 hematological toxicities, significant nephrotoxicity, or significant xerostomia (grade ≥3) was observed during the follow-up of 9 ± 5 months.

Intensified RLT with dose escalation of the first 3 cycles to 10-11 GBq in patients with high-volume mCRPC may increase the efficacy of the treatment, with a toxicity profile comparable with the standard treatment scheme. High response rates and a strong safety profile warrant further investigation in select patients.