Role of F-18–NaF PET/CT in Patients With Metastatic Castration-Resistant Prostate Cancer Treated With Enzalutamide

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In a phase II study reported in the Journal of Clinical Oncology, Kyriakopoulos et al found that use of quantitative total bone imaging with fluorine-18 (F-18)–sodium fluoride (NaF) positron-emission tomography/computed tomography (PET/CT) helped identify heterogeneity of response in bone lesions in patients with metastatic castration-resistant prostate cancer treated with enzalutamide.

As stated by the investigators, “Intrapatient treatment response heterogeneity is underrecognized. Quantitative total bone imaging using [F-18–NaF] PET/CT scans is a tool that allows characterization of interlesional treatment response heterogeneity in bone. Understanding spatial-temporal response is important to identify individuals who may benefit from treatment beyond progression.”

Study Details

In the study, 22 evaluable men with progressive disease and at least two lesions on bone scintigraphy were treated with 160 mg of enzalutamide daily. F-18–NaF PET/CT scans were obtained at baseline (PET1); week 13 (PET2); and at the time of prostate-specific antigen (PSA) progression, standard radiographic or clinical progression, or at 2 years without progression (PET3). Lesion level response was determined by quantitative total bone imaging. The primary endpoint was the proportion of men with at least one responding bone lesion on PET3 using quantitative total bone imaging.

Key Findings

Treatment duration ranged from 1.4 to 34.1 months. All 22 men had at least one lesion still responding to treatment at the time of PSA, radiographic, or clinical progression or 2 years after treatment initiation (PET3). A total of 19 had PSA progression at PET3, including 3 with radiographic bone progression on bone scan. A total of 3 had no progression at 2 years after treatment initiation.

The mean number of lesions at PET1 was 58. The proportion of progressive lesions increased from a mean of 7.8% at PET2 to a mean of 9.4% at PET3. All patients had a mixture of progressive or new, stable, and responding lesions at PET3.

Overall, global standardized uptake value (SUV) metrics decreased during enzalutamide treatment (PET2) and increased at the time of progression (PET3). The greatest predictor of PSA progression was change in SUVhetero (variance of lesion SUVmean, with greater global score indicating greater heterogeneity) from PET1 to PET3, with a hazard ratio of 3.88 (95% confidence interval [CI] = 1.24–2.1). Overall functional disease burden improved during enzalutamide treatment, but an increase in total burden (SUVtotal) was observed with PET/CT at the time of progression.

The investigators concluded, “We found that the proportion of progressing lesions was low, indicating that a substantial number of lesions appear to continue to benefit from enzalutamide beyond progression. Selective targeting of nonresponding lesions may be a reasonable approach to extend benefit.”

Glenn Liu, MD, of the University of Wisconsin Carbone Cancer Center, University of Wisconsin, Madison, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Pfizer and Astellas Pharma. For full disclosures of the study authors, visit

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