Patients and surgery
Two hundred ninety-one patients were referred for clinical FCH PET-CT followed by prostatectomy with ePLND at Skåne University Hospital in Malmö and Lund, Sweden, from January 2015 to November 2018. One hundred eleven patients were excluded due to incomplete data within their medical records, denied participation or examination on another PET-CT system, as shown in Fig. 1. After exclusions, 180 patients with biopsy-verified intermediate or high-risk prostate cancer were enrolled into the study.
EPLND was performed using a standard template including the area of the iliac bifurcation, along the external and internal iliac vessels, and the obturator fossa. All surgical procedures and histopathological examinations were performed in the Department of Urology at Skåne University Hospital, Malmö, Sweden.
The PET-CT examination clinical reports were compared with the histopathology reports after ePLND for the presence of lymph node metastases on a per-patient and per-side basis.
This study was approved by the regional review board in Lund (#2016/417 and 2018/753) and performed according to the Declaration of Helsinki. All patients provided written informed consent.
PET-CT systems
Examination images were acquired on one of the following PET-CT systems; Philips Gemini TF PET-CT (Gemini Time of Flight; Philips Healthcare, Cleveland, OH, USA) or GE Discovery MI PET-CT (Discovery MI; GE Healthcare, Milwaukee, WI, USA).
The Philips Gemini TF PET-CT systems were installed in 2006 and discontinued in 2017 in the Department of Medical Imaging and Physiology, Skåne University Hospital in Malmö, and Lund. The system used lutetium–yttrium oxyorthosilicate crystals (crystal size, 4.0 × 4.0 × 22 mm3) coupled to an array of PM tubes. The PET-detector had an axial field of view of 17.6 cm and the bed positions had an overlap of 50%. According to the National Electrical Manufactures Association standards, the sensitivity was 7 cps/kBq. The system had a 16-slice CT.
For reconstruction, the BLOB-OS-TOF algorithm was used, with three iterations, 33 subsets, and a 5-mm Gaussian post filter. The matrix size was 144 x 144 (voxel size, 4 x 4 x 4 mm) and time-of-flight and CT attenuation corrections were included. The CT scans were acquired with diagnostic quality, using a 5-mm reconstructed slice thickness, a pitch factor of 0.938, rotation speed of 0.75 s, 120 kV, and high-beam tube current modulation (120–300 mA) based on the patient’s total body mass. For the CT, a filtered back projection reconstruction was used.
The GE Discovery MI PET-CT systems were installed in 2017 in the Department of Medical Imaging and Physiology, Skåne University Hospital in Malmö, and Lund. The system uses lutetium–yttrium oxyorthosilicate crystals (crystal size, 4.0 x 5.3 x 25 mm3) coupled to an array of SiPM. The PET-detector has an axial field of view of 20 cm and the bed position has an overlap of 24%. According to the National Electrical Manufactures Association standards, the sensitivity is 13 cps/kBq. The system has a 128-slice CT.
PET image reconstruction was performed using BSREM including time-of-flight, the point-spread function, and CT-based attenuation correction with a 256 x 256 matrix (pixel size, 2.7 x 2.7 mm2; slice thickness, 2.8 mm) and a β value of 500 (13). The diagnostic CT was performed with the tube current modulation applied and the tube current was adjusted for each patient, with a noise index of 42.25. A 100-kV tube voltage was used for a body mass index (BMI) that was less than 30 kg/m2, and 120 kV was used when the BMI was greater than 30 kg/m2. An adaptive statistical iterative reconstruction technique was used for the CT images.
PET-CT imaging and interpretation
FCH was administrated intravenously at a dose of 4 MBq/kg after a minimum fasting time of 4 hours. A whole-body PET-CT was acquired after an accumulation time of 60 minutes on either one of the PET-CT systems. The images on both PET-CT systems were acquired from the upper thigh to the base of the skull with 2.0 minutes per bed position.
Each PET-CT examination was interpreted by one nuclear medicine physician and one radiologist who jointly wrote a clinical report. Lymph node FCH uptake that exceeded that of the mediastinal blood pool were generally considered to be abnormal. Eight experienced nuclear medicine physicians have worked and interpreted FCH PET images in our department from 2015 to 2018. Among these eight physicians, seven interpreted images on both PET-CT systems. For this study, one of the nuclear medicine physicians (ET, with 7 years of experience in reading FCH images), reviewed the clinical reports and sorted the patients into the following two groups: suspected/possible lymph node metastases and without lymph node metastases. When the clinical report was ambiguous (for example possible but not certain metastases), the patient was considered to have abnormal lymph nodes in the subsequent analysis.
Statistical analysis
Clinical and pathological information was retrospectively obtained from medical records. Comparison of baseline variables for patients who were examined using the Discovery MI and Gemini TF was performed using a Chi-square test and a Mann–Whitney U-test. The overall diagnostic performance was analysed using the receiver operating characteristics (ROC) analyses. Per-patient and per-side (left and right) sensitivity, specificity, PPV, and NPV were calculated on the different PET-CTs within the ePLND template using histology results from the ePLND as the reference method. Confidence intervals for the respective groups were 95%. Statistical significance was considered for P less than 0.05. Statistical analyses were performed using IBM SPSS version 26 (IBM Corp., Armonk, NY, USA) and Stata 16.0 (StataCorp LLC, College Station, TX, USA).