TY - JOUR
T1 - 177Lu-PSMA-I&T for Treatment of Metastatic Castration-Resistant Prostate Cancer
T2 - Prognostic Value of Scintigraphic and Clinical Biomarkers
AU - Karimzadeh, Amir
AU - Heck, Matthias
AU - Tauber, Robert
AU - Knorr, Karina
AU - Haller, Bernhard
AU - D'Alessandria, Calogero
AU - Weber, Wolfgang A.
AU - Eiber, Matthias
AU - Rauscher, Isabel
N1 - Publisher Copyright:
© 2023 by the Society of Nuclear Medicine and Molecular Imaging.
PY - 2023/3/1
Y1 - 2023/3/1
N2 - The aim of this retrospective analysis was to determine prostate-specific antigen (PSA) response, PSA progression-free survival (PFS), and overall survival (OS) in a large cohort of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with 177Lu-PSMA-I&T and to identify clinical and scintigraphic prognostic factors for outcome. Methods: In total, 301 consecutive mCRPC patients were included in this analysis. Prognostic factors included clinical parameters, routine laboratory parameters, and findings on posttreatment scintigraphy. Scintigraphic tumor uptake of 177Lu-PSMA-I&T was compared with salivary gland uptake and classified as high or low. The longest extent of skeletal metastatic disease was measured, and its changes during therapy were used to define scintigraphic progression, response, and stable disease. A PSA response of at least 50%, PSA PFS, and OS were calculated. Results: In total, 1,138 cycles (median, 3 cycles per patient) of 177Lu-PSMA-I&T using a standard activity of 7.4 GBq were applied intravenously every 4-10 wk (median, 6 wk). Overall, 34% (95% CI, 28%-38%) of patients showed a PSA response of at least 50%, and the median PSA PFS and OS of the total patient cohort were 16.0 wk (95% CI, 12.1-19.9) and 13.8 mo (95% CI, 12.4-15.5), respectively. Patients with high scintigraphic tumor uptake showed a higher PSA response rate of at least 50% (45.7% vs. 10.4%; P < 0.0001) and a significantly reduced risk of PSA progression (median event time, 24.9 vs. 9.0 wk; hazard ratio, 0.3; 95% CI, 0.2-0.5; P < 0.0001). In our data, risk of death was not significantly different between patients with high scintigraphic uptake and those with low scintigraphic uptake (median, 14.4 vs. 12.4 mo; hazard ratio, 0.9; 95% CI, 0.6-1.3; P = 0.6). In a multivariable analysis, the following pretherapeutic prognostic factors for OS were identified: alkaline phosphatase, lactate dehydrogenase, and PSA levels; prior chemotherapy; and the presence of visceral metastases. Scintigraphic response was a strong prognostic factor for PSA response, PSA PFS, and OS after 1 treatment cycle. Conclusion: This retrospective analysis of a large group of consecutive patients corroborates previous clinical experience for 177Lu-PSMA-I&T in mCRPC and establishes previously proposed prognostic factors. The skeletal tumor extent and its changes were identified as new potential biomarkers to predict the outcome of therapy after the first treatment cycle.
AB - The aim of this retrospective analysis was to determine prostate-specific antigen (PSA) response, PSA progression-free survival (PFS), and overall survival (OS) in a large cohort of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with 177Lu-PSMA-I&T and to identify clinical and scintigraphic prognostic factors for outcome. Methods: In total, 301 consecutive mCRPC patients were included in this analysis. Prognostic factors included clinical parameters, routine laboratory parameters, and findings on posttreatment scintigraphy. Scintigraphic tumor uptake of 177Lu-PSMA-I&T was compared with salivary gland uptake and classified as high or low. The longest extent of skeletal metastatic disease was measured, and its changes during therapy were used to define scintigraphic progression, response, and stable disease. A PSA response of at least 50%, PSA PFS, and OS were calculated. Results: In total, 1,138 cycles (median, 3 cycles per patient) of 177Lu-PSMA-I&T using a standard activity of 7.4 GBq were applied intravenously every 4-10 wk (median, 6 wk). Overall, 34% (95% CI, 28%-38%) of patients showed a PSA response of at least 50%, and the median PSA PFS and OS of the total patient cohort were 16.0 wk (95% CI, 12.1-19.9) and 13.8 mo (95% CI, 12.4-15.5), respectively. Patients with high scintigraphic tumor uptake showed a higher PSA response rate of at least 50% (45.7% vs. 10.4%; P < 0.0001) and a significantly reduced risk of PSA progression (median event time, 24.9 vs. 9.0 wk; hazard ratio, 0.3; 95% CI, 0.2-0.5; P < 0.0001). In our data, risk of death was not significantly different between patients with high scintigraphic uptake and those with low scintigraphic uptake (median, 14.4 vs. 12.4 mo; hazard ratio, 0.9; 95% CI, 0.6-1.3; P = 0.6). In a multivariable analysis, the following pretherapeutic prognostic factors for OS were identified: alkaline phosphatase, lactate dehydrogenase, and PSA levels; prior chemotherapy; and the presence of visceral metastases. Scintigraphic response was a strong prognostic factor for PSA response, PSA PFS, and OS after 1 treatment cycle. Conclusion: This retrospective analysis of a large group of consecutive patients corroborates previous clinical experience for 177Lu-PSMA-I&T in mCRPC and establishes previously proposed prognostic factors. The skeletal tumor extent and its changes were identified as new potential biomarkers to predict the outcome of therapy after the first treatment cycle.
KW - 177Lu-PSMA-I&T
KW - clinical biomarkers
KW - metastatic castration-resistant prostate cancer (mCRPC)
KW - prognostic factors
KW - scintigraphic biomarkers
UR - http://www.scopus.com/inward/record.url?scp=85149428121&partnerID=8YFLogxK
U2 - 10.2967/jnumed.122.264402
DO - 10.2967/jnumed.122.264402
M3 - Article
C2 - 36137758
AN - SCOPUS:85149428121
SN - 0161-5505
VL - 64
SP - 402
EP - 409
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 3
ER -