Composite Prediction Score to Interpret Bone Focal Uptake in Hormone-Sensitive Prostate Cancer Patients Imaged with [18F]PSMA-1007 PET/CT

Matteo Bauckneht; Francesca D’Amico; Domenico Albano; Michele Balma; Camilla Cabrini; Francesco Dondi; Tania Di Raimondo; Virginia Liberini; Luca Sofia; Simona Peano; Mattia Riondato; Giuseppe Fornarini; Riccardo Laudicella; Luca Carmisciano; Egesta Lopci; Roberta Zanca; Marcello Rodari; Stefano Raffa; Maria Isabella Donegani; Daniela Dubois; Leonardo Peñuela; Cecilia Marini; Francesco Bertagna; Alberto Papaleo; Silvia Morbelli; Gianmario Sambuceti; Marta Ponzano; Alessio Signori

doi:10.2967/jnumed.124.267751

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FIGURE 1.
Patient inclusion flow chart shows patient selection. Center A: University of Genova; Center B: University of Brescia; Center C: S. Croce e Carle Hospital, Cuneo; Center D: Humanitas Research Hospital, Rozzano. CRPC = castration-resistant prostate cancer.
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FIGURE 2.
Model discrimination. Receiver-operating-characteristic (ROC) curve (red line) shows mean cvAUC, resulting after 10-fold cross-validation (dashed lines).
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FIGURE 3.
Internal calibration plot shows deviation from 45° line of perfect fit (red) at 95% CI (light gray) and 99% CI (dark gray).
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FIGURE 4.
Emblematic examples of bone uptake of [¹⁸F]PSMA-1007 lead to varying probabilities of bone metastases when BUMP score is applied. According to BUMP score results, 4 cases with increasing probabilities of bone metastases are shown in panels top to bottom.
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FIGURE 5.
Decision-curve analysis demonstrates clinical net benefit against threshold probability associated with using BUMP score for interpreting focal bone uptake in hormone-sensitive PCa patients imaged with [¹⁸F]PSMA-1007 PET/CT.

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TABLE 1.

Clinical Characteristics and Imaging Data for Bone Uptake of [¹⁸F]PSMA-1007

	Training cohort (total n = 448)	External validation cohort (total n = 89)
Clinical setting
Primary	255 (56.9)	24 (27.0)
Restaging	193 (43.1)	65 (73.0)
Initial PSA (ng/mL)	10.2 (6.3–22.9)	10.6 (5.6–227)
ISUP grade group
1	25 (5.6)	16 (18.0)
2	99 (22.1)	6 (6.7)
3	114 (25.5)	17 (19.1)
4	112 (25.0)	10 (11.2)
5	66 (14.7)	40 (44.9)
Missing	32 (7.1)	0 (0.0)
PSA at PET/CT (ng/mL)	6.3 (1.5–16.4)	3.0 (0.52–17)
ADT at PET/CT
No	343 (76.6)	63 (70.8)
Yes	104 (23.2)	26 (29.2)
Unknown	1 (0.2)	0 (0)
PSMA injected dose (MBq)	311 (277–342)	352 (337–362)
Uptake time (min)	95.0 (90.0–117.0)	73.0 (60.0–88.0)
Bone uptake site
Ribs	145 (32.4)	27 (30.3)
Spine	120 (26.7)	17 (19.1)
Pelvis	132 (29.5)	24 (27.0)
Other sites	51 (11.4)	21 (23.6)
HU_mean	192.4 (131–277.4)	157 (111–248)
HU_max	663 (455–837)	412 (268–669)
SUV_max	5.2 (4.0–9.7)	5.6 (4–12.7)
PSMA visual score	1.0 (1.0–2.0)	1.0 (1.0–3.0)
PSMA-TV (mL)	1.8 (1–3.3)	1.4 (0.7–3.1)
TL-PSMA	6.6 (3.8–14.4)	4.8 (2.4–14.4)

PSA = prostate-specific antigen; ISUP = International Society of Urological Pathology; PSMA-TV = PSMA tumor volume; TL-PSMA = total lesion PSMA.
Qualitative data are number and percentage. Continuous data are median and interquartile range.

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TABLE 2.

Univariate and Multivariate Analyses Identifying Determinants of the BUMP Score

Parameter	Nonmetastatic (total n = 260)	Metastatic (total n = 188)	Univariate analyses		Multivariate analyses
Parameter	Nonmetastatic (total n = 260)	Metastatic (total n = 188)	OR	P	OR	P
Clinical setting
Primary staging	167 (65.5)	88 (34.5)	1.00 (Ref)
Restaging	93 (48.2)	100 (51.8)	2.04 (1.18–3.52)	0.010	—	NS
Initial PSA (ng/mL)	8.7 (6.0–16.5)	14.0 (7.7–33.0)	1.48 (1.16–1.88)	0.001	—	NS
ISUP grade group
1	17 (68.0)	8 (32.0)	1.00 (Ref)
2	77 (77.8)	22 (22.2)	0.61 (0.18–2.08)
3	70 (61.4)	44 (38.6)	1.34 (0.41–4.32)
4	53 (47.3)	59 (52.7)	2.37 (0.71–7.92)
5	31 (47.0)	35 (53.0)	2.40 (0.70–8.26)	0.009	—	NS
Missing	12 (37.5)	20 (62.5)	—	—
PSA at PET/CT (ng/mL)	6.2 (1.1–13.0)	6.8 (3.0–27.0)	1.19 (1.02–1.38)	0.027	—	NS
ADT at PET/CT
No	230 (67.1)	113 (32.9)	1.00 (Ref)		1.00 (Ref)
Yes	30 (28.8)	74 (71.2)	5.02 (2.62–9.63)	<0.001	4.06 (1.91–8.67)	<0.001
Unknown	0 (0)	1 (100)	—	—
PSMA injected dose (MBq)	309.0 (277.0–339.5)	312.0 (281.0–343.0)	1.03 (0.98–1.08)	0.277
Uptake time (min)	96.0 (90.0–116.0)	95.0 (90.0–117.0)	1.01 (0.88–1.16)	0.902
Bone uptake site
Ribs	104 (71.7)	41 (28.3)	1.00 (Ref)
Spine	70 (58.3)	50 (41.7)	1.81 (1.19–2.76)
Pelvis	66 (50.0)	66 (50.0)	2.54 (1.61–3.99)
Other sites	20 (39.2)	31 (60.8)	3.93 (1.96–7.89)	<0.001	—	NS
HU_mean	180.6 (118.3–247.0)	211.4 (150.9–320.5)	1.03 (1.01–1.05)	0.001	1.04 (1.02–1.06)	<0.001
HU_max	592.0 (420.0–790.0)	744.5 (541.0–926.0)	1.02 (1.01–1.02)	<0.001	—	NS
SUV_max	4.5 (3.7–5.6)	10.2 (5.2–21.9)	1.35 (1.25–1.46)	<0.001	1.39 (1.27–1.52)	<0.001
PSMA visual score	1.0 (1.0–1.0)	2.0 (1.0–3.0)	2.38 (1.79–3.17)	<0.001	—	NS
PSMA-TV (mL)^*	1.8 (1.1–3.0)	1.8 (0.9–3.7)	1.00 (0.96–1.05)	0.947
TL-PSMA^*	5.0 (3.4–9.2)	11.1 (5.0–30.0)	1.02 (1.01–1.04)	0.012	—	NS

↵* Variables were evaluated independently in multivariate analysis to avoid collinearity instability.
OR = odds ratio; Ref = reference value; NS = not significant; PSA = prostate-specific antigen; ISUP = International Society of Urological Pathology; PSMA-TV = PSMA tumor volume; TL-PSMA = total lesion PSMA.
Qualitative data are number and percentage. Continuous data are median and interquartile range. OR data are number and 95% CI in parentheses.

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TABLE 3.
Penalized Coefficients After 10-Fold Cross-Validation Lasso Model
Parameter Penalized regression coefficients
Intercept −4.660246
ADT at time of PET/CT 1.690656
HU_mean 0.0043016
SUV_max 0.317027