SUVmean on baseline [18F]PSMA-1007 PET and clinical parameters are associated with survival in prostate cancer patients scheduled for [177Lu]Lu-PSMA I&T

Abstract

Background: Quantification of [⁶⁸ Ga]-labeled PSMA PET predicts response in patients with prostate cancer (PC) who undergo PSMA-targeted radioligand therapy (RLT). Given the increasing use [¹⁸F]-labeled radiotracers, we aimed to determine whether the uptake derived from [¹⁸F]PSMA-1007 PET can also identify responders and to assess its prognostic value relative to established clinical parameters.

Methods: We retrospectively analyzed 103 patients with metastatic, castration-resistant PC who were treated with [¹⁷⁷Lu]Lu-PSMA I&T. We calculated SUV_mean, SUV_max, PSMA-avid tumor volume (TV), and total lesion PSMA (defined as PSMA-TV*SUV_mean) on pre-therapeutic [¹⁸F]PSMA-1007 PET. Laboratory values for hemoglobin, C-reactive protein (CRP), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alkaline phosphatase (AP) were also collected prior to RLT. We performed univariable Cox regression followed by multivariable and Kaplan-Meier analyses with overall survival (OS) serving as endpoint. Last, we also computed a risk factor (RF) model including all items reaching significance on multivariable analysis to determine whether an increasing number of RFs can improve risk stratification.

Results: A total of 48 patients died and median OS was 16 months. On univariable Cox regression, SUV_mean, CRP, LDH, hemoglobin, and the presence of liver metastases were significantly associated with OS. On multivariable Cox regression, the following significant prognostic factors for OS were identified: SUV_mean (per unit, HR, 0.91; P = 0.04), the presence of liver metastases (HR, 2.37; P = 0.03), CRP (per mg/dl, HR, 1.13; P = 0.003), and hemoglobin (per g/dl, HR, 0.76; P < 0.01). Kaplan-Meier analysis showed significant separation between patients with a SUV_mean below or above a median SUV_mean of 9.4 (9 vs 19 months, HR 0.57; P = 0.03). Of note, patients with only one RF (median OS not reached) showed longest survival compared to patients with two (11 months; HR 2.43 95% CI 1.07-5.49, P = 0.02) or more than two RFs (7 months; HR 3.37 95% CI 1.62-7.03, P < 0.001).

Conclusion: A lower SUV_mean derived from [¹⁸F]PSMA-1007, higher CRP, lower hemoglobin, and the presence of liver metastases are associated with reduced OS in patients undergoing RLT. An early RF model also demonstrated that an increasing number of those factors is linked to worse outcome, thereby emphasizing the importance of clinical and imaging parameters for adequate risk stratification.

Keywords: Overall survival; PSMA; Prostate cancer; Radioligand therapy; Theranostics; [177Lu]Lu-PSMA I&T; [18F]PSMA-1007.