Prognostic 18F-flotufolastat PET parameters for outcome assessment of 177Lu-labeled PSMA-targeted radioligand therapy in metastatic castration-resistant prostate cancer

Eur J Nucl Med Mol Imaging. 2025 May;52(6):2041-2050. doi: 10.1007/s00259-024-07003-2. Epub 2025 Jan 23.

Abstract

Purpose: This retrospective analysis evaluates baseline 18F-flotufolastat positron emission tomography (PET) parameters as prognostic parameters for treatment response and outcome in patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing treatment with [177Lu]Lu-PSMA-I&T.

Methods: A total of 188 mCRPC patients with baseline 18F-flotufolastat PET scans were included. Tumor lesions were semiautomatically delineated, with imaging parameters including volume-based and standardized uptake value (SUV)-based metrics. Outcome measures included prostate-specific antigen (PSA) response, PSA-progression-free survival (PSA-PFS), and overall survival (OS). Univariate and multivariate regression analyses assessed the impact of baseline imaging and pretherapeutic clinical parameters on outcome. Event time distributions were estimated with the Kaplan-Meier method, and groups were compared with log-rank tests.

Results: Significant prognostic parameters for PSA response and PSA-PFS included log-transformed whole-body SUVmax (odds ratio (OR), 3.26, 95% confidence interval (CI), 2.01-5.55 and hazard ratio (HR), 0.51, 95% CI, 0.4-0.66; both p < 0.001) and prior chemotherapy (OR 0.3, 95% CI, 0.12-0.72 and HR 1.64, 95% CI, 1.07-2.58; p = 0.008 and p = 0.028, respectively). For OS, significant prognosticators were the following log-transformed parameters: number of lesions (HR 1.38, 95% CI, 1.24-1.53; p < 0.001), TTV (HR 1.27, 95% CI, 1.18-1.37; p < 0.001), and ITLV (HR 1.24, 95% CI, 1.16-1.33; p < 0.001), with log-transformed TTV (HR 1.15, 95% CI, 1.04-1.27; p = 0.008) remaining significant in multivariate analysis.

Conclusion: At baseline, SUV-based 18F-flotufolastat PET metrics (e.g., whole-body SUVmax) serve as significant positive prognosticators for short-term outcomes (PSA response and PSA-PFS). In contrast, volume-based metrics (e.g., TTV) are significant negative prognosticators for long-term outcome (OS), in mCRPC patients treated with [177Lu]Lu-PSMA-I&T.

Keywords: 18F-flotufolastat; PSMA; Radioligand therapy; [177Lu]Lu-PSMA-I&T; mCRPC.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, Surface* / metabolism
  • Glutamate Carboxypeptidase II* / metabolism
  • Humans
  • Lutetium* / therapeutic use
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Positron-Emission Tomography*
  • Prognosis
  • Prostatic Neoplasms, Castration-Resistant* / diagnostic imaging
  • Prostatic Neoplasms, Castration-Resistant* / metabolism
  • Prostatic Neoplasms, Castration-Resistant* / pathology
  • Prostatic Neoplasms, Castration-Resistant* / radiotherapy
  • Radioisotopes / therapeutic use
  • Radiopharmaceuticals / therapeutic use
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Lutetium
  • Glutamate Carboxypeptidase II
  • Lutetium-177
  • FOLH1 protein, human
  • Radioisotopes
  • Antigens, Surface
  • Radiopharmaceuticals