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Research ArticleClinical Investigation

A Prostate-Specific Membrane Antigen PET-Based Approach for Improved Diagnosis of Prostate Cancer in Gleason Grade Group 1: A Multicenter Retrospective Study

Jingliang Zhang, Fei Kang, Jie Gao, Jianhua Jiao, Zhiyong Quan, Shuaijun Ma, Yu Li, Shikuan Guo, Zeyu Li, Yuming Jing, Keying Zhang, Fa Yang, Donghui Han, Weihong Wen, Jing Zhang, Jing Ren, Jing Wang, Hongqian Guo and Weijun Qin
Journal of Nuclear Medicine November 2023, 64 (11) 1750-1757; DOI: https://doi.org/10.2967/jnumed.122.265001
Jingliang Zhang
1Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, China;
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Fei Kang
2Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an, China;
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Jie Gao
3Department of Urology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Institute of Urology, Nanjing University, Nanjing, China;
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Jianhua Jiao
1Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, China;
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Zhiyong Quan
2Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an, China;
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Shuaijun Ma
1Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, China;
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Yu Li
1Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, China;
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Shikuan Guo
1Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, China;
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Zeyu Li
1Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, China;
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Yuming Jing
1Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, China;
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Keying Zhang
1Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, China;
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Fa Yang
1Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, China;
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Donghui Han
1Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, China;
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Weihong Wen
4Institute of Medical Research, Northwestern Polytechnical University, Xi’an, China;
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Jing Zhang
5Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi’an, China; and
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Jing Ren
6Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
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Jing Wang
2Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an, China;
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Hongqian Guo
3Department of Urology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Institute of Urology, Nanjing University, Nanjing, China;
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Weijun Qin
1Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, China;
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  • FIGURE 1.
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    FIGURE 1.

    Flowchart of study design.

  • FIGURE 2.
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    FIGURE 2.

    Overlap of SUVmax and overlap of PSMA intensity in patients with TRUS-guided biopsy GG1 and SUVmax < 12. Distribution of [68Ga]PSMA PET/CT SUVmax demonstrated higher SUVmax in csPCa than in non-csPCa. However, between values of 2.9 (dashed gray line) and 9.2 (solid gray line), there was SUVmax overlap between csPCa and non-csPCa. Subsequently, 56 patients’ index-lesion slides corresponding to SUVmax were selected and made into 2 consecutive tissue sections. After this, 2 consecutive tissue sections were subjected to hematoxylin-eosin and PSMA immunohistochemistry staining and digital scanning. Resulting hematoxylin-eosin and PSMA images were segmented into 500 × 500 μm tiles. Deep learning was used to identify and cluster hematoxylin-eosin tiles, whereas PSMA tiles were matched with their corresponding hematoxylin-eosin tiles on basis of sample name and spatial coordinates of 2 consecutive tissue sections. Finally, according to categories of hematoxylin-eosin tiles, PSMA tiles were correspondingly labeled benign gland, GP3, and GP4 and randomly selected (n = 1,000 for each category) to calculate PSMA H-score using ImageJ software (National Institutes of Health). **P < 0.01 by Mann–Whitney test (overlap of SUVmax) and Kruskal–Wallis test (overlap of PSMA intensity). ****P < 0.0001 by Mann–Whitney test (overlap of SUVmax) and Kruskal–Wallis test (overlap of PSMA intensity). HE = hematoxylin-eosin.

  • FIGURE 3.
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    FIGURE 3.

    Representative case of prostatic evasive anterior tumor shown on [68Ga]PSMA PET/CT in axial, coronal, and sagittal views (from left to right). Representative case was previously underestimated as indolent PCa on basis of TRUS-guided biopsy result (biopsy GG1 and 1/13 positive core). [68Ga]PSMA PET/CT (PRIMARY score, 4; SUVmax, 10.1) identified case as csPCa (RP GG2).

  • FIGURE 4.
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    FIGURE 4.

    Relationships among SUVmax, PRIMARY score, and csPCa probability. (A) Nomogram of model of 10 × PRIMARY score + 2 × SUVmax for individual csPCa prediction. (B) Contour plot of csPCa probability according to 10 × PRIMARY score and 2 × SUVmax.

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    FIGURE 5.

    Correction of misdiagnoses by model 1. (A) Patient with PI-RADS score of 3, biopsy GG1, PRIMARY score of 4, SUVmax of 5.5, and positive model 1 score of 51 (∼60% csPCa probability). Lesion pointed at with arrow was missed by MRI but was detected by PRIMARY score and model 1. Postoperative pathology confirmed csPCa (GG2). (B) Patient with PI-RADS score of 4, PRIMARY score of 3, SUVmax of 6.26, and negative model 1 score of 42.52 (∼40% csPCa probability). Lesion pointed at with arrow was identified as csPCa by PI-RADS score and PRIMARY score but was suggested as non-csPCa by model 1. Postoperative pathology confirmed non-csPCa (type of benign prostatic disease called atypical adenomatous hyperplasia). ADC = apparent diffusion coefficient; DWI = diffusion-weighted imaging; HE = hematoxylin-eosin.

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    TABLE 1.

    Demographic and Clinical Characteristics of 56 Patients Investigated in This Study

    Baseline characteristicEntire cohort, n = 56Xijing cohort, n = 42Nanjing cohort, n = 14
    Age (y)67 (62, 70)65 (61, 70)70 (67, 74)
    PSA at PET/CT (ng/mL)9.28 (6.10, 14.71)9.66 (6.65, 15.18)8.09 (5.86, 13.56)
    PV (mL)41.02 (26.46, 58.95)39.49 (26.46, 52.02)41.18 (27.85, 60.31)
    SUVmax5.50 (3.63, 7.66)4.86 (3.30, 6.44)7.49 (6.43, 9.40)
    PRIMARY score (%)
     15 (8.93)4 (9.52)1 (7.14)
     215 (26.79)13 (30.95)2 (14.29)
     37 (12.50)4 (9.52)3 (21.43)
     429 (51.79)21 (50.00)8 (57.14)
    RP ISUP GG (%)
     Benign0 (0)0 (0)0 (0)
     GG130 (53.57)24 (57.14)6 (42.86)
     GG221 (37.50)14 (33.33)7 (50.00)
     GG33 (5.36)3 (7.14)0 (0)
     GG42 (3.57)1 (2.38)1 (7.14)
     GG50 (0)0 (0)0 (0)
    TRUS
     Normal28226
     Abnormal28208
    DRE
     Normal26197
     Abnormal30237
    PI-RADS score
     13 (6.38)3 (9.09)0 (0)
     26 (12.77)6 (18.18)0 (0)
     314 (29.79)8 (24.24)6 (42.86)
     414 (29.79)8 (24.24)6 (42.86)
     510 (21.28)8 (24.24)2 (14.29)
    • PSA, prostate-specific antigen; PV, prostate volume; ISUP, International Society of Urological Pathology; DRE, digital rectal examination.

    • Qualitative data are number and percentage; continuous data are median and interquartile range.

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    TABLE 2.

    Comparison of Performance and Discriminative Ability of Model 1 and Other Diagnostic Methods

    CohortDiagnostic methodAUCAICP value*
    Entire cohort, n = 56Model 1, cutoff value† = 45.250.8359 (0.7233–0.9484)60.46—
    SUVmax, cutoff value = 7.30.7353 (0.6006–0.8699)68.680.048
    PRIMARY score, 5–3 vs. 2–10.7257 (0.6159–0.8354)68.000.009
    MRI subgroup, n = 47Model 1, cutoff value = 45.250.8364 (0.7114–0.9614)52.02—
    SUVmax, cutoff value = 7.60.7555 (0.6112–0.8997)56.680.127
    PRIMARY score, 5–3 vs. 2–10.6918 (0.5678–0.8158)60.820.002
    PI-RADS score, 5–4 vs. 3–10.7036 (0.5703–0.8370)60.960.149
    PI-RADS score, 5–3 vs. 2–10.6373 (0.5339–0.7407)62.540.014
    • ↵* Difference compared with model 1.

    • ↵† Cutoff value corresponding to highest level of accuracy (minimal false-negative and false-positive results) for model 1 and SUVmax.

    • AIC = Akaike information criterion.

    • AUC data in parentheses are 95% CI.

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Journal of Nuclear Medicine: 64 (11)
Journal of Nuclear Medicine
Vol. 64, Issue 11
November 1, 2023
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A Prostate-Specific Membrane Antigen PET-Based Approach for Improved Diagnosis of Prostate Cancer in Gleason Grade Group 1: A Multicenter Retrospective Study
Jingliang Zhang, Fei Kang, Jie Gao, Jianhua Jiao, Zhiyong Quan, Shuaijun Ma, Yu Li, Shikuan Guo, Zeyu Li, Yuming Jing, Keying Zhang, Fa Yang, Donghui Han, Weihong Wen, Jing Zhang, Jing Ren, Jing Wang, Hongqian Guo, Weijun Qin
Journal of Nuclear Medicine Nov 2023, 64 (11) 1750-1757; DOI: 10.2967/jnumed.122.265001

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A Prostate-Specific Membrane Antigen PET-Based Approach for Improved Diagnosis of Prostate Cancer in Gleason Grade Group 1: A Multicenter Retrospective Study
Jingliang Zhang, Fei Kang, Jie Gao, Jianhua Jiao, Zhiyong Quan, Shuaijun Ma, Yu Li, Shikuan Guo, Zeyu Li, Yuming Jing, Keying Zhang, Fa Yang, Donghui Han, Weihong Wen, Jing Zhang, Jing Ren, Jing Wang, Hongqian Guo, Weijun Qin
Journal of Nuclear Medicine Nov 2023, 64 (11) 1750-1757; DOI: 10.2967/jnumed.122.265001
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Keywords

  • PET
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  • diagnosis
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