Abstract:
Metastatic prostate carcinoma overexpresses prostate-specific membrane
antigen (PSMA), making this antigen a suitable target for
radioligand therapy of the disease. Here we report on our experience
with a series of 73 castration-resistant prostate carcinoma
patients treated with 225Ac-PSMA-617, identifying variables predictive
for overall survival (OS) and progression-free survival (PFS) after
225Ac-PSMA-617 treatment. METHODS : 225Ac-PSMA-617 was administered
to patients who had metastatic castration-resistant prostate
carcinoma and who had exhausted available therapy options
for their disease. Full blood count, glomerular filtration rate, and liver
function test were obtained at baseline and on follow-up for evaluation
of toxicity. 68Ga-PSMA PET/CT was obtained at baseline,
before every treatment cycle, and on follow-up for selection of patients
for treatment, to determine the activity of the treatment agent
to be administered, and for response assessment. Serial prostatespecific
antigen (PSA) was obtained for PSA response assessment.
RESULTS : Seventy-three men (mean age, 69 y; range, 45–85 y) with
metastatic castration-resistant prostate carcinoma were treated
with 210 cycles of 225Ac-PSMA-617. In 70% of patients, a PSA
decline of greater than or equal to 50% was obtained; 82% of patients
had any PSA decline. In 29% of patients, all lesions on 68Ga-
PSMA PET resolved in response to treatment. During follow-up, 23
patients experienced disease progression, whereas 13 patients
died from their disease. The estimated median PFS and OS were
15.2 mo (95% CI, 13.1–17.4) and 18 mo (95% CI, 16.2–19.9), respectively.
In univariate analyses, factors such as baseline PSA, any
PSA decline, PSA decline of greater than or equal to 50%, prior
chemotherapy, prior radiation therapy, and baseline hemoglobin seen in 5 patients with baseline renal impairment. CONCLUSION : In
this study, a PSA decline of greater than or equal to 50% after
treatment with 225Ac-PSMA-617 was proven by multivariate analyses
to be significantly associated with OS and PFS. Furthermore,
previous 177Lu-PSMA treatment was negatively associated with
PFS in both univariate and multivariate analyses.
