Background: ¹⁸F-Flotufolastat (¹⁸F-rhPSMA-7.3) is a newly approved high affinity PSMA-targeting PET radiopharmaceutical for diagnostic imaging in patients with prostate cancer (PCa). SPOTLIGHT (NCT04186845) evaluated ¹⁸F-flotufolastat in patients with recurrent PCa. Here, we report available SPOTLIGHT data to assess the impact of ¹⁸F-flotufolastat on planned treatment after curative-intent primary therapy. Methods: Patients underwent PET 50–70 min after IV administration of 296 MBq ¹⁸F-flotufolastat. The protocol instructed onsite investigators to record patients’ management plans (MP) before and after ¹⁸F-flotufolastat PET. These MP were compared and categorized as: ‘no change’, ‘major change’, ‘other change’, ‘additional information required’ or ‘intended plan not valid’. A ‘major change’ was defined as a change to treatment modality (e.g., salvage radiation therapy [RT] to systemic therapy), while ‘other change’ represented a change within a modality (e.g., modified RT field). Plans categorized as ‘no change’, ‘major change’ or ‘other change’ were considered evaluable. All imaging data were subsequently submitted for blinded image evaluation (BIE) by 3 central readers. Results: Of 389 patients who had ¹⁸F-flotufolastat PET, 97 had sufficient MP data for evaluation. These 97 patients were comparable to the overall population in terms of prior treatment (84% vs 79%, respectively, were post-prostatectomy), Gleason Score (63% vs 60% had Score 7), and median baseline PSA (0.8 vs 1.1 ng/mL). Moreover, BIE data show the detection rate in this subgroup (81/97; 84%) to be equivalent to that in the overall population (322/389; 83%). Most patients, 86/97 (89%) had a change to their MP post-scan. A ‘major change’ was noted for 78 (80%) patients, while 8 (8.2%) had an ‘other change’ (Table). Onsite imaging reads show that both positive and negative ¹⁸F-flotufolastat scans influenced MP. While 88% of revisions occurred after a positive scan, 75% of those whose MP were revised to watchful waiting (WW) had negative scans. All patients with MP revised from salvage therapy to non-curative systemic therapy had distant/extrapelvic ¹⁸F-flotufolastat-avid lesions. Conclusions:¹⁸F-Flotufolastat located recurrence sites in the majority of patients with recurrent PCa, frequently resulting in major changes to MP. Treatment based on visualization of ¹⁸F-flotufolastat-avid lesions may facilitate optimal targeting of recurrence sites and avoid futile salvage therapy. Future studies of the outcome of such MP changes are warranted. Clinical trial information: NCT04186845.