Research ArticleClinical Investigation

177Lu-PSMA-I&T for Treatment of Metastatic Castration-Resistant Prostate Cancer: Prognostic Value of Scintigraphic and Clinical Biomarkers

Amir Karimzadeh, Matthias Heck, Robert Tauber, Karina Knorr, Bernhard Haller, Calogero D’Alessandria, Wolfgang A. Weber, Matthias Eiber and Isabel Rauscher
Journal of Nuclear Medicine March 2023, 64 (3) 402-409; DOI: https://doi.org/10.2967/jnumed.122.264402

Article Figures & Data

Figures

  • Figure
  • FIGURE 1.
    FIGURE 1.

    Waterfall plot showing response to treatment as measured by serum PSA. Best PSA response is defined as smallest increase or greatest decrease in PSA from baseline compared with color-coded 177Lu-PSMA ligand uptake in posttherapeutic whole-body scintigraphy. First 21 columns represent patients with increase of >100% as best PSA response. Red = patients with low scintigraphic uptake on posttherapeutic scintigraphy; green = patients with high scintigraphic uptake on posttherapeutic scintigraphy.

  • FIGURE 2.
    FIGURE 2.

    A 69-y-old patient with bone metastases presenting with high scintigraphic uptake (A) and a 76-y-old patient with bone and lymph node metastases presenting with low scintigraphic uptake (B) on posttherapeutic whole-body scintigraphy at first cycle of 177Lu-PSMA-I&T. PSA PFS and OS were 58 wk and 24 mo, respectively, in patient A and 17 wk and 10 mo, respectively, in patient B.

  • FIGURE 3.
    FIGURE 3.

    Kaplan–Meier survival curves for PSA PFS and OS stratified by high and low uptake on posttherapeutic scintigraphy: PSA PFS (A) and OS (B) in total patient cohort, and PSA PFS (C) and OS (D) in patients without visceral metastases.

  • FIGURE 4.
    FIGURE 4.

    Waterfall plot showing response to treatment as measured by serum PSA. Best PSA response is compared with color-coded change in infiltration length on posttherapeutic scintigraphy. First 16 columns represent patients with increase of >100% as best PSA response. Green = patients with response (>0.5 cm decrease in infiltration length between first and second cycles); yellow = stable disease (±0.5-cm change in infiltration length); red = progression (>0.5 cm increase).

  • FIGURE 5.
    FIGURE 5.

    (A) An 81-y-old patient with bone, lymph node, and liver metastases presenting with metastatic disease in right femur with extent of 10.8 cm on posttherapeutic whole-body scintigraphy at first cycle of 177Lu-PSMA-I&T. (B) Same patient with decrease in infiltration length to 3.0 cm at second cycle of 177Lu-PSMA-I&T. Change in infiltration length was −7.8 cm, and classification was therefore scintigraphic response. PSA PFS and OS were 24 wk and 22 mo, respectively.

  • FIGURE 6.
    FIGURE 6.

    Kaplan–Meier survival curves stratified by scintigraphic response (>0.5-cm decrease in infiltration length between first and second cycles), scintigraphically stable disease (±0.5-cm change in infiltration length), and scintigraphic progression (>0.5-cm increase) for PSA PFS (A) and OS (B).

Tables

  • TABLE 1.

    Baseline Patient Characteristics

    CharacteristicData
    No. of patients301
    Age (y), n = 30173 (67–77)
    PSA (ng/mL), n = 29799.5 (20.4–290.3)
    LDH (U/L), n = 297263.5 (218–344)
    AP (U/L), n = 297112 (72–231)
    Hemoglobin (g/dL), n = 29711.7 (10.3–12.8)
    Prior systemic therapies for mCRPC, n = 301
     Docetaxel213
     Cabazitaxel48
     Abiraterone252
     Enzalutamide183
     223Ra41
     Previous chemotherapy214
    No. of prior mCRPC therapies, n = 301
     1105
     2109
     368
     418
     54
    Site of metastasis, n = 301
     Lymph node, overall216
     Lymph node only (N1+/M1a)22
     Bone overall274
     Bone (M1b, without visceral metastases)215
     Visceral, overall (M1c)64
     Liver26
     Lung31
     Adrenal21

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

  • TABLE 2.

    Uni- and Multivariable Analysis for Association of Baseline Variables with OS

    Univariable analysisMultivariable analysis
    VariableNo. of patientsHR95% CIPHR95% CIP
    High scintigraphic uptake295
     No96Reference
     Yes1990.90.6–1.20.30.80.6–1.10.2
    Age, continuous2951.01.0–1.00.31.01.0–1.00.6
    AP per 50 U/L increase, continuous2951.01.0–1.10.0001*1.01.0–1.10.02*
    LDH per 50 U/L increase, continuous2951.01.0–1.1<0.0001*1.01.0–1.10.001*
    Hemoglobin, continuous2951.01.0–1.00.71.01.0–1.00.4
    PSA per 50 ng/mL increase, continuous2951.01.0–1.00.0001*1.01.0–1.00.01*
    ≥2 pretreatments295
     No98Reference
     Yes1971.41.0–1.90.11.30.8–2.00.3
    Previous 223Ra295
     No254Reference
     Yes411.00.7–1.50.90.80.5–1.20.3
    Previous chemotherapy295
     No84Reference
     Yes2111.51.1–2.20.02*1.10.7–1.70.7
    Bone metastases (M1b, without visceral metastases)211ReferenceReference
    Lymph node only metastases (N+/M1a)210.30.1–0.70.007*0.40.2–1.00.05
    Visceral metastases (M1c)631.51.1–2.00.03*1.51.0–2.10.02*

    • ↵* Statistically significant.

  • TABLE 3.

    Uni- and Multivariable Analysis for Association of Changes in Various Parameters with OS

    Univariable analysisMultivariable analysis
    Change in…No. of patientsHR95% CIPHR95% CIP
    Infiltration length per 10-mm increase, continuous1821.11.1–1.3<0.0001*1.21.1–1.3<0.0001*
    AP per 20% increase, continuous1821.01.0–1.10.131.01.0–1.10.3
    LDH per 20% increase, continuous1821.21.1–1.30.001*1.21.0–1.30.01*
    Hemoglobin per 20% decrease, continuous1821.00.8–1.40.611.00.8–1.40.8
    PSA per 20% increase, continuous1821.01.0–1.10.03*1.01.0–1.00.8

    • ↵* Statistically significant.

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