177Lu-PSMA-I&T for Treatment of Metastatic Castration-Resistant Prostate Cancer: Prognostic Value of Scintigraphic and Clinical Biomarkers

Amir Karimzadeh, Matthias Heck, Robert Tauber, Karina Knorr, Bernhard Haller, Calogero D'Alessandria, Wolfgang A. Weber, Matthias Eiber, Isabel Rauscher

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)402-409
Number of pages8
JournalJournal of Nuclear Medicine
Volume64
Issue number3
DOIs
StatePublished - 1 Mar 2023
Externally publishedYes

Keywords

  • 177Lu-PSMA-I&T
  • clinical biomarkers
  • metastatic castration-resistant prostate cancer (mCRPC)
  • prognostic factors
  • scintigraphic biomarkers

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