Daniel Koehler et al., European Journal of Nuclear Medicine and Molecular Imaging, 2023.
Summary
To identify reasons for negative histopathology of specimens from prostate-specifc membrane antigen (PSMA) radioguided surgery (PSMA-RGS) in recurrent prostate cancer (PCa) after prostatectomy.
Of 302 patients who underwent PSMA-RGS, 17 (5.6%) demonstrated a negative histopathology. Preoperative data, PSMA PET, PSMA SPECT, and follow-up information were analyzed retrospectively to diferentiate true/false positive (TP/ FP) from true/false negative (TN/FN) lesions.
The median prostate-specifc antigen at PET was 0.4 ng/ml (interquartile range [IQR] 0.3–1.2). Twenty-fve index lesions (median short axis 7 mm, IQR 5–8; median long-axis 12 mm, IQR 8–17) had a median SUVmax of 4 (IQR 2.6–6; median PSMA expression score 1, IQR 1–1). Six lesions were TP, twelve were FP, one was TN, and six remained unclear. All TP lesions were in the prostatic fossa or adjacent to the internal iliac arteries. Three suspected local recurrences were FP. All FP lymph nodes were located at the distal external iliac arteries or outside the pelvis. A low PSMA-expressing TN node was identifed next to a common iliac artery. Unclear lesions were located next to the external iliac arteries or outside the pelvis.
In most cases with a negative histopathology from PSMA-RGS, lesions were FP on PSMA PET. Unspecifc uptake should be considered in low PSMA-expressing lymph nodes at the distal external iliac arteries or outside the pelvis, especially if no PSMA-positive lymph nodes closer to the prostatic fossa are evident. Rarely, true positive metastases were missed by surgery or histopathology.
Keywords: Prostate cancer · PSA recurrence · PSMA PET/CT · PSMA-radioguided surgery
Results from AnyScan® TRIO SPECT/CT/PET
Patients received a median dose of 750 MBq (interquartile range [IQR] 704–771) [ 99mTc]Tc-PSMA-I&S at a median time of 17.7 h (IQR 17.2–18.2) prior to SPECT/CT. [ 99mTc] Tc-PSMA-I&S was produced under the conditions of §13 (2b) of the Arzneimittelgesetz (German Medicinal Products Act) as reported previously [19]. SPECT/CT acquisition was performed with a Mediso AnyScan® TRIO (Mediso Medical Imaging Systems, Budapest, Hungary) or a Siemens Sym[1]bia Intevo™ 16 (Siemens Healthineers, Erlangen, Germany). Whole body planar scans were acquired with 120 mm/min scan speed. SPECT of the abdomen and pelvis were obtained in a 128 × 128 matrix with 96 frames per rotation in 40 sec[1]onds per stop (Mediso AnyScan® Trio) or 64 frames per rota[1]tion in 20 seconds per stop (Symbia Intevo™ 16). The fol[1]lowing CT was conducted with 100–130 kV and an adaptive dose modulation. CT images were obtained in a 512 × 512 matrix and 0.6-mm slice thickness. Data were reconstructed in 3 dimensions with a slice thickness of 3 mm. All lesions that were identifed on prior PSMA PET/CT scans were evalu[1]ated qualitatively using a visual 4-point scale (0 = no visible uptake, 1 = minimal uptake [only perceivable in knowledge of the PET result], 2 = moderate uptake, 3 = intense uptake).
Table 1. Imaging characteristics of preoperative PSMA PET scans and [99mTc]Tc-PSMA-I&S SPECT/CT
Fig. 1. Prostate-specifc antigen trend after prostate-specifc membrane antigen (PSMA) radioguided surgery (RGS). Spaghetti plot illustrating the preoperative prostate-specifc antigen (PSA) value and the follow-up PSA after PSMA-RGS. Green – PSA decrease >50%; yellow – PSA change ≤50%; red – PSA increase >50%
Fig. 2. Sankey diagram of the lesion-based review of all index lesions
Fig. 3. Index lesion distribution and status after retrospective analysis. The number of lesions that were assessed as true positive/false positive/true negative/ additional true positive/unclear are provided in circles next to their respective locations. CIL = common iliac left, CIR = common iliac right, EIL = external iliac left, EIR = external iliac right, IIL = internal iliac left, IIR = internal iliac right, M1b= bone lesion, RP = retroperitoneal, Tr = local recurrenc
Conclusion
In most cases with a negative histopathological result of the resected specimens from PSMA-RGS, the identified target lesions were false positive on the preoperative PSMA PET. Unspecific uptake should be considered in low PSMA-expressing lymph nodes next to the distal external iliac arteries or outside the pelvis, especially if no other PSMA-positive lymph nodes closer to the prostatic fossa are evident. Rarely, metastases were not successfully reached during surgery or missed in the histopathological workup.
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