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

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.

Fig. 1

(A) A 70-year-old patient with lymph node metastases, showing 17 tumor lesions, a total tumor volume (TTV) of 31 ml, and an intensity-weighted total lesion volume (ITLV) of 55 ml. (B) A 77-year-old patient with bone metastases, showing 139 tumor lesions, a TTV of 322 ml, and an ITLV of 626 ml. PSA-PFS and OS were 5.4 months and 54.9 months for patient A, compared to 1.8 months and 12.0 months for patient B. The number of lesions, TTV, and ITLV were semiautomatically assessed, with tumor lesions shown in pink

Fig. 2

Kaplan-Meier survival curves for the risk stratification model, which includes baseline imaging and pretherapeutic clinical parameters that reached significance in the multivariate Cox regression analysis for OS. The model consists of the upper median values for total tumor volume (TTV) and lactate dehydrogenase (LDH) levels, the lower median value for hemoglobin (Hb), and the presence of visceral metastases. Each parameter represents one risk factor (RF). Patients were stratified based on the number of RFs: 0 RF (green line), 1–2 RFs (blue line), and 3–4 RFs (red line)