The diagnostic value of PET/CT imaging with the (68)Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer

Ali Afshar-Oromieh, Eleni Avtzi, Frederik L Giesel, Tim Holland-Letz, Heinz G Linhart, Matthias Eder, Michael Eisenhut, Silvan Boxler, Boris A Hadaschik, Clemens Kratochwil, Wilko Weichert, Klaus Kopka, Jürgen Debus, Uwe Haberkorn, Ali Afshar-Oromieh, Eleni Avtzi, Frederik L Giesel, Tim Holland-Letz, Heinz G Linhart, Matthias Eder, Michael Eisenhut, Silvan Boxler, Boris A Hadaschik, Clemens Kratochwil, Wilko Weichert, Klaus Kopka, Jürgen Debus, Uwe Haberkorn

Abstract

Purpose: Since the introduction of positron emission tomography (PET) imaging with (68)Ga-PSMA-HBED-CC (=(68)Ga-DKFZ-PSMA-11), this method has been regarded as a significant step forward in the diagnosis of recurrent prostate cancer (PCa). However, published data exist for small patient cohorts only. The aim of this evaluation was to analyse the diagnostic value of (68)Ga-PSMA-ligand PET/CT in a large cohort and the influence of several possibly interacting variables.

Methods: We performed a retrospective analysis in 319 patients who underwent (68)Ga-PSMA-ligand PET/CT from 2011 to 2014. Potential influences of several factors such as prostate-specific antigen (PSA) level and doubling time (DT), Gleason score (GSC), androgen deprivation therapy (ADT), age and amount of injected tracer were evaluated. Histological verification was performed in 42 patients after the (68)Ga-PSMA-ligand PET/CT. Tracer uptake was measured in 901 representative tumour lesions.

Results: In 82.8% of the patients at least one lesion indicative of PCa was detected. Tumor-detection was positively associated with PSA level and ADT. GSC and PSA-DT were not associated with tumor-detection. The average maximum standardized uptake value (SUVmax) of tumour lesions was 13.3 ± 14.6 (0.7-122.5). Amongst lesions investigated by histology, 30 were false-negative in 4 different patients, and all other lesions (n = 416) were true-positive or true-negative. A lesion-based analysis of sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) revealed values of 76.6%, 100%, 91.4% and 100%. A patient-based analysis revealed a sensitivity of 88.1%. Of 116 patients available for follow-up, 50 received local therapy after (68)Ga-PSMA-ligand PET/CT.

Conclusion: (68)Ga-PSMA-ligand PET/CT can detect recurrent PCa in a high number of patients. In addition, the radiotracer is highly specific for PCa. Tumour detection is positively associated with PSA and ADT. (68)Ga-PSMA-ligand PET/CT can help delay systemic therapy of PCa.

Figures

Fig. 1
Fig. 1
68Ga-PSMA-ligand PET/CT demonstrating two different patients with small lymph node metastases and different intensity of tracer uptake. Both patients had GSC 7. According to our experiences and the histological analysis, even low 68Ga-PSMA-HBED-CC accumulations in lesions outside the prostate gland have to be regarded as PCa-specific until proven otherwise. Red arrows point to lymph node metastases. Colour scales were automatically produced by the PET/CT machine. a CT of the first patient, b CT of the second patient, c fusion of PET and CT of the first patient, d fusion of PET and CT of the second patient
Fig. 2
Fig. 2
A patient with multifocal PCa (a, c) and another patient (b, d) with unifocal PCa with a rarely seen inguinal lymph node metastasis. Red arrows point to PCa within the prostate gland and blue arrow points to an inguinal lymph node metastasis. Both patients had GSC 7, although the tumours present with different contrast. Colour scales were automatically produced by the PET/CT machine. a Low-dose CT of the patient with a multifocal PCa, c corresponding fusion of PET and low-dose CT 1 h p.i., b low-dose CT of the patients with the unifocal PCa, d corresponding fusion of PET and low-dose CT 1 h p.i.
Fig. 3
Fig. 3
Probability of a pathological 68Ga-PSMA-ligand PET/CT as histogram (above) and plot of the rates of pathological PET/CTs with confidence intervals (below) depending on PSA levels in 311 patients. Blue columns include the number of pathological PET/CTs and their rate in %
Fig. 4
Fig. 4
Probability of a pathological 68Ga-PSMA-ligand PET/CT as histogram (above) and plot of the rates of pathological PET/CTs with confidence intervals (below) depending on GSC in 284 patients. Blue columns include the number of pathological PET/CTs and their rate in %
Fig. 5
Fig. 5
Average SUVmean/SUVmax values of ten patients who received excretion stimulus between the first 68Ga-PSMA-ligand PET/CT (1 h p.i.) and the second PET/CT (3 h p.i.). As demonstrated, the excretion stimulus did not reduce the high physiological radiotracer uptake of the salivary glands

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Source: PubMed

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