Abstract:
PURPOSE : 225Ac-PSMA-617 has demonstrated good anti-tumor effect as a treatment option for metastatic castration-resistant
prostate cancer (mCRPC) patients. No study has previously assessed treatment outcome and survival following 225Ac-
PSMA-617 treatment of de novo metastatic hormone-sensitive prostate carcinoma (mHSPC) patients. Based on the potential
side effects that are known and explained to the patients by the oncologist, some of the patients refused the standard treatment
and are seeking alternative therapies. Thus, we report our preliminary findings in a retrospective series of 21 mHSPC
patients that refused standard treatment options and were treated with 225Ac-PSMA-617.
METHODS : We retrospectively reviewed patients with histologically confirmed de novo treatment-naïve bone ± visceral
mHSPC that were treated with 225Ac-PSMA-617 radioligand therapy (RLT). Inclusion criteria included an Eastern Cooperative
Oncology Group (ECOG) performance status of 0 to 2, treatment-naive bone ± visceral mHSPC, and patients refusal
for ADT ± docetaxel, abiraterone acetate, or enzalutamide. We evaluated the response to treatment using prostate-specific
antigen (PSA) response and the progression-free survival (PFS) and overall survival (OS) as well as the toxicities.
RESULTS : Twenty-one mHSPC patients were included in this preliminary work. Following treatment, twenty patients (95%)
had any decline in PSA and eighteen patients (86%) presented with a PSA decline of ≥ 50% including 4 patients in whom
PSA became undetectable. A lower percentage decrease in PSA following treatment was associated with increased mortality
and shorter progression-free survival. Overall, administration of 225Ac-PSMA-617 was well tolerated. The commonest
toxicity seen was grade I/II dry mouth observed in 94% of patients.
CONCLUSIONS : Given these favorable results, randomized prospective multicenter trials assessing the clinical value of 225Ac-PSMA-617
as a therapeutic agent for mHSPC administered either as monotherapy or administered concomitant with ADT are of interest.
