Prognostic Value of Restaging [ ¹⁸ F]FDG PET/CT in Patients with Metastatic Castration-Resistant Prostate Cancer Undergoing [ ¹⁷⁷ Lu]Lu-PSMA-617 Therapy

We analyzed the prognostic value of an interim [¹⁸F]FDG PET/CT performed after cycle 3 of [¹⁷⁷Lu]Lu-PSMA-617 ([¹⁷⁷Lu]Lu-PSMA) for patients undergoing therapy for metastatic castration-resistant prostate cancer (mCRPC). <b>Methods:</b> We retrospectively reviewed the data of patients with mCRPC in the ProsTIC Registry (NCT04769817) receiving [¹⁷⁷Lu]Lu-PSMA who underwent [¹⁸F]FDG PET/CT at both baseline and after cycle 3. Parameters included visual response assessment (progression vs. no progression) and metabolic tumor volume (MTV) (≥20% increase vs. &lt;20% increase or any decrease). Outcomes were measured against reductions of 50% or greater in prostate-specific antigen (PSA) levels (PSA-50) by Fisher exact test and time-to-event outcomes. PSA progression-free survival (PFS) and overall survival (OS) were defined relative to cycle 3, using Kaplan–Meier estimation. <b>Results:</b> Thirty-four patients (median age, 72 y; interquartile range, 66–77 y) were eligible for study inclusion. Their median PSA was 58 ng/mL (interquartile range, 17–176 ng/mL) before treatment. All patients had prior treatment with androgen receptor pathway inhibitors, and 33 had received at least 1 line of chemotherapy. Visual progression on interim [¹⁸F]FDG PET was observed in 18 patients (53%) and was associated with shorter median PFS after cycle 3 (1.2 mo; 95% CI, 0.7–2.0) compared with those patients without visual progression (5.2 mo; 95% CI, 3.6–7.0) (<i>P</i> = 0.0005) and lower achievement of PSA-50 (28% vs. 75%, <i>P</i> = 0.015). Median OS did not significantly differ between those with and without visual progression (10.3 mo; 95% CI, 6.1–17.1 mo vs. 16.4 mo; 95% CI, 10.5–21.4 mo, respectively) (<i>P</i> = 0.090). An increase of at least 20% in MTV was observed in 11 patients (32%) who, when compared with those whose MTV increased or decreased by less than 20%, had a shorter median PFS (0.7 mo; 95% CI, 0.6–1.4 mo vs. 4.9 mo; 95% CI, 2.2–6.6 mo; <i>P</i> &lt; 0.0001) and OS (10.8 mo; 95% CI, 2.1–17.1 mo vs. 16.4 mo; 95% CI, 10.3–20.1 mo; <i>P</i> = 0.069) and lower PSA-50 response (9.1% vs. 70%, <i>P</i> = 0.002). <b>Conclusion:</b> Visual and quantified changes on interim [¹⁸F]FDG PET appeared prognostic for PFS in patients undergoing [¹⁷⁷Lu]Lu-PSMA therapy and correlated with PSA response. Further studies are needed to determine whether [¹⁸F]FDG PET could serve as an independent biomarker to guide treatment intensification or de-escalation, including treatment pauses.