Prospective evaluation of 18F-NaF and 18F-FDG PET/CT in detection of occult metastatic disease in biochemical recurrence of prostate cancer

Abstract

Purpose: This study aimed to perform a prospective evaluation of 18F-NaF and 18F-FDG PET/CT in the detection of occult metastatic disease in men with prostate cancer and biochemical relapse.

Methods: Thirty-seven men with prostate-specific antigen (PSA) relapse (median, 3.2 ng/mL; range, 0.5-40.2 ng/mL) after definitive therapy for localized prostate cancer [26 radical prostatectomy (RP), 11 external beam radiation therapy] and negative conventional imaging underwent 18F-FDG and 18F-NaF PET/CT on 2 separate days within the same week. Studies were interpreted by 2 experienced radiologists in consensus for abnormal uptake suspicious for metastatic disease. The reference standard was a combination of imaging and clinical follow-up. Rank of PSA values for positive and negative PET/CT was compared using analysis of variance adjusting for primary therapy. Association between PSA and scan positivity in patients with RP was evaluated using Wilcoxon rank sum test.

Results: Result of the 18F-FDG PET/CT scan was positive for nodal disease in 2 patients. True-positive detection rate for occult osseous metastases by 18F-NaF PET/CT was 16.2%. Median PSA levels for positive versus negative PET/CT scans were 4.4 and 2.9 ng/mL, respectively, with the difference marginally significant in prostatectomized men (P=0.072). Percentages of patients with either 18F-NaF- or 18F-FDG-positive PET/CT in RP and external beam radiation therapy were 10% (n=10) and undefined (n=0) for a PSA of 2 ng/mL or less, 29% (n=7) and 50% (n=2) for PSA greater than 2 ng/mL but 4 ng/mL or less, 60% (n=5) and 40% (n=5) for PSA greater than 4 ng/mL but 10 ng/mL or less, and 25% (n=4) and 25% (n=4) for PSA greater than 10 ng/mL, respectively.

Conclusions: In biochemical relapse of prostate cancer, 18 F-NaF PET/CT is useful in the detection of occult osseous metastases, whereas the yield of 18F-FDG PET/CT is relatively limited. 18F-NaF PET/CT positivity tends to associate with increasing PSA level in prostatectomized men and may occur in lower PSA ranges than conventionally recognized.

FIGURE 1

Patient 28 in Table 1: Images of a 65-year-old man with biochemically recurrent prostate cancer post RP (PSA, 29.3 ng/mL; Gleason score 3+5). A, ¹⁸F-NaF PET/CT maximum intensity projection. B, ¹⁸F-FDG PET/CT maximum intensity projection. C, Fused ¹⁸F-NaF PET/CT. D, Fused ¹⁸F-FDG PET/CT. ¹⁸F-NaF PET/CT demonstrated randomly distributed osseous metastases. However, only the lesion in left posterior ilium was concordantly active on ¹⁸F-FDG PET/CT (arrows). The patient was started on docetaxel with a subsequent fall in serum PSA level to 4.25 ng/mL at 3 months after PET/CT scans.

FIGURE 2

Patient 17 in Table 1: Images of an 84-year-old man with biochemically recurrent prostate cancer post RP (PSA, 3.1 ng/mL; Gleason score 4+5). ¹⁸F-NaF PET/CT (A) showed a lesion in posterior left acetabulum (arrowheads) that was negative on ¹⁸F-FDG PET/CT (B). However, ¹⁸F-FDG PET/CT (C) also demonstrated 2 isolated hypermetabolic (SUVmax, 3) subcentimeter left common iliac lymph nodes (arrow) and left ureteral urine activity (arrowhead). The patient was continued on androgen deprivation therapy.

FIGURE 3

Box-and-whisker plot of the PSA values (log scale) at the time of PET/CT scans for patients with negative PET/CT scans comparing to those with 1 or more positive PET/CT scans. The difference in median PSA levels between the groups was not significant (P = 0.42). The line inside the box, box margins, and whisker margins represent the median value, interquartile ranges, and ranges, respectively.

FIGURE 4

Values (log scale) of PSA at the time of PET/CT scans stratified by the patients’ primary therapy (RP or EBRT) and scan positivity. Patients with previous RP showed a marginally higher median PSA level in the positive PET/CT group in comparison to those with negative PET/CT scans (4.6 vs 2.1 ng/mL, P = 0.072).

FIGURE 5

Percent of patients with 1 or more positive PET/CT scans grouped by PSA range (ng/mL).