Prospective Head-to-Head Comparison of 18F-PSMA PET/CT and 18F-NaF PET/CT for Assessing Bone Metastases in 160 Patients with Newly Diagnosed High-Risk Prostate Cancer

Claus Madsen; Dan Fuglø; Maria Pedersen; Rikke Broholm; Peter B. Østergren; Rasmus Bisbjerg; Per Kongsted; Kayalvili Nielsen; Christian Haarmark; Helle Zacho

doi:10.2967/jnumed.124.268275

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FIGURE 1.
Flowchart illustrating process of achieving final diagnosis of bone metastases on patient level.
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FIGURE 2.
Flowchart illustrating inclusion process of study participants.
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FIGURE 3.
Patient with discordant findings on baseline ¹⁸F-NaF and ¹⁸F-PSMA PET/CT. (A) Maximum-intensity projection and axial projection of ¹⁸F-NaF PET/CT scan with no evidence of bone metastases. (B) ¹⁸F-PSMA PET/CT scan showing 2 lesions, one in left ilium and another in right costa 6, which were suspected of being bone metastases (red arrows). Third faint lesion in right ilium was not interpreted as bone metastasis (green arrows). Because of absence of metastatic lesions on ¹⁸F-NaF PET/CT (conventional scan), patient was observed, without treatment. (C and D) Follow-up scans conducted 6 months later revealed detectable uptake in lesion in right ilium on ¹⁸F-NaF PET/CT and increasing uptake on ¹⁸F-PSMA PET/CT (orange arrows). There are multiple ¹⁸F-PSMA-avid lymph nodes on follow-up scan.
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FIGURE 4.
Sankey diagram of number of bone metastases detected by ¹⁸F-NaF PET/CT and ¹⁸F-PSMA PET/CT in 44 patients with bone metastases according to reference standard. bm = bone metastases.

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TABLE 1.

Demographic Data of Study Population

Demographic	Data
Mean age (y)	72 (range, 54–88)
Median PSA (ng/mL)	35 (range, 2.3–7,701)
PSA category (n)
<10 ng/mL	28 (18%)
10–20 ng/mL	22 (14%)
20.1–49.9 ng/mL	50 (31%)
50–99.9 ng/mL	28 (18%)
≥100 ng/mL	32 (20%)
cT-stage (n)
Tx	9 (6%)
T1	12 (8%)
T2a-T2b	13 (8%)
T2c	21 (13%)
T3	83 (52%)
T4	22 (14%)
ISUP grade group (n)
1–2	23 (14%)
3	57 (36%)
4–5	80 (50%)

PSA = prostate-specific antigen; cT-stage = clinical tumor stage; ISUP = International Society of Urological Pathology.

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TABLE 2.

Patients with Discordant Findings on ¹⁸F-NaF PET/CT and ¹⁸F-PSMA PET/CT and with Repeated Scans 6 Months Later

Patient	PSA	cT-stage	ISUP	Treatment between baseline and follow-up scans	Bone metastases on ¹⁸F-NaF PET/CT	Bone metastases on ¹⁸F-PSMA PET/CT	Bone metastases, reference standard^*
36	64	T1c	3	EBRT to prostate and pelvic lymph nodes and ADT with LHRH agonist with curative intent	Yes—one lesion near right ischial tuberosity	No—only low uptake near right ischial tuberosity	Yes—increasing uptake on follow-up ¹⁸F-NaF and ¹⁸F-PSMA; increasing sclerotic appearance
50	89	T4	4	ADT with LHRH agonist. Bicalutamide for 30 d	No	Yes—high uptake in left ilium and low uptake in sacrum	Yes—no change on follow-up ¹⁸F-NaF and ¹⁸F-PSMA; from all available data, disseminated bone disease on baseline is assumed
79	104	T3b	5	ADT with LHRH agonist	No	Yes—multiple small bone metastases	Yes—some lesions (left costa 1 and Th12) become osteoblastic on follow-up CT
86	20	T3a	5	Small cell component; treated with ADT (LHRH agonist) and carboplatin and etoposide	No	Yes—small lesion in left femoral neck	No—¹⁸F-PSMA uptake becomes slightly faint on follow-up scan; lack of visible ¹⁸F-NaF uptake on follow-up is unchanged; no osteoblastic formation
117	4.8	T2c	4	EBRT to prostate and pelvic lymph nodes and ADT with LHRH agonist with curative intent	No—uptake in left ilium interpreted benign	Yes—high uptake in left ilium	Yes—lesion becomes faint on follow-up ¹⁸F-NaF and ¹⁸F-PSMA; small osteoblastic formation
190	25	T2a	4	Watchful waiting	No	Yes—high uptake in left ilium and right costa 6	Yes—new lesion in right ilium on follow-up ¹⁸F-NaF and ¹⁸F-PSMA; multiple new ¹⁸F-PSMA-avid lymph nodes on follow-up

↵* Reference standard is determined in multidisciplinary team conference and is based on baseline and follow-up PET/CT scans and available clinical data.
PSA = prostate-specific antigen; cT-stage = clinical tumor stage; ISUP = International Society of Urological Pathology; EBRT = external-beam radiation therapy; ADT = androgen deprivation therapy; LHRH = luteinizing hormone–releasing hormone.

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TABLE 3.

Diagnostic Performances at Patient Level

Imaging modality	¹⁸F-PSMA PET/CT	¹⁸F-NaF PET/CT
Sensitivity	0.98 (0.88–1.00)	0.91 (0.78–0.97)
Specificity	0.99 (0.95–1.00)	1.00 (0.97–1.00)
PPV	0.98 (0.88–1.00)	1.00 (0.91–1.00)
NPV	0.99 (0.95–1.00)	0.97 (0.92–0.99)
Accuracy	0.99 (0.96–1.00)	0.97 (0.94–0.99)
True-positive	43 (27%)	40 (25%)
False-positive	1 (1%)	0 (0%)
True-negative	115 (72%)	116 (73%)
False-negative	1 (1%)	4 (3%)

PPV and NPV = positive and negative predictive value, respectively.
Data in parentheses are 95% CI or percentage.

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TABLE 4.

Proportion of Scans with Confident Conclusions, Stratified by Number of Bone Metastases

Bone metastases (n)	Scans with confident conclusions
Bone metastases (n)	NaF	PSMA
0	108/120 (90%)	103/116 (89%)
1	1/8 (13%)	4/7 (57%)
2	1/3 (33%)	2/3 (67%)
3–5	7/7 (100%)	6/6 (100%)
>5	22/22 (100%)	28/28 (100%)
Total	139/160 (87%)	143/160 (89%)