11C-acetate PET/MRI in bladder cancer staging and treatment response evaluation to neoadjuvant chemotherapy: a prospective multicenter study (ACEBIB trial)

Abstract

Background: To evaluate the accuracy of 11C-acetate Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) in bladder cancer (BC) staging and monitoring response to neoadjuvant chemotherapy (NAC).

Methods: Eighteen patients were prospectively enrolled. Fifteen treatment naive patients underwent 11C-acetate PET/MRI before transurethral resection of bladder tumor (TUR-BT) for primary tumor evaluation. Five patients with muscle invasive BC were imaged after NAC and prior to radical cystectomy (RC) with extended pelvic lymph node dissection (ePLND) for NAC treatment response evaluation. Two patients were part of both cohorts. 11C-acetate PET/MRI findings were correlated with histopathology. Accuracy for lymph node detection was evaluated on patient and the ePLND template (10 regions) levels.

Results: The sensitivity, specificity and accuracy of 11C-acetate PET/MRI for the detection of muscle invasive BC was 1.00, 0.69 and 0.73 while the area under the receiver operating characteristic curve (95% confidence interval) was 0.85 (0.55-1.0), respectively. All five NAC patients underwent chemotherapy as planned and 11C-acetate PET/MRI correctly staged three patients, overstaged one and understaged one patient compared with RC and ePLND findings. A total of 175 lymph node were removed, median of 35 (range, 27-43) per patient in five patients who had RC and ePLND while 12 (7%) harboured metastases. Sensitivity, specificity, accuracy and AUC for N-staging were 0.20, 0.96, 0.80 and 0.58 on the ePLND template (10 regions) level.

Conclusions: 11C-acetate PET/MRI is feasible for staging of BC although sensitivity for the detection of nodal metastases is low. Monitoring response to NAC shows promise and warrants evaluation in larger studies.

Trial registration: ClinicalTrials.gov Identifier: NCT01918592 , registered August 8 2013.

Keywords: 11C-acetate; Bladder cancer; Neoadjuvant chemotherapy; PET/MRI.

Conflict of interest statement

The authors declare that they have no competing interests.

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Figures

Fig. 1

Examined lymph node areas in radical cystectomy

Fig. 2

Flow chart of the study protocol. The trial consisted of two phases: in phase 1 accuracy of 11C-acetate PET/MRI was evaluated on 15 treatment naive patients before any intervention of primary tumor. In phase 2 treatment response to Neoadjuvant chemotherapy (NAC) was evaluated in 5 patients undergoing 11C-acetate PET/MRI after transurethral resection of bladder tumor (TUR-BT) and neoadjuvant chemotherapy. 2 patients participated in both phases of the study. In total, 18 patients were enrolled

Fig. 3

Pre-transurethral resection 11C-acetate PET/MRI (a, b, c) in a 75-year old male patient (number 3 in primary imaging) showing a heterogenous lobulated mass on the left side of mid-line without extension (white arrow) to perivesical fat on T2-weighted image (a) or an area of increased diffusion signal restriction (white arrow) extending beyond the bladder wall (b - b value 800 s/mm2 trace diffusion weighted image). The lesion had increased 11C-acetate uptake (c - PET fused with T2-weighted image, SUV is scaled from 0.0 to 3.2). The imaging findings were suggestive of T1 stage. The transurethral resection of bladder tumor specimen revealed stage T1, thus the findings of 11C-acetate PET/MRI correctly staged the tumor

Fig. 4

Comparison of local bladder cancer staging (T-stage) on pre-transurethral resection (a, b, c) and post-chemotherapy 11C-acetate PET/MRI (d, e, f) in a 63-year-old male patient (number 12 in primary imaging). A heterogenous lobulated mass on the right side of mid-line with extension (white arrow) to perivesical fat seen on T2-weighted image (a), an area of increased diffusion signal restriction (white arrow) beyond the bladder wall (b - b value 800 s/mm2 trace diffusion weighted image), an associated right sided hydroureter, and increased 11C-acetate uptake (c - PET fused with T2-weighted image, SUV is scaled from 0.0 to 3.5) suggestive of T3 stage. On post-chemotherapy 11C-acetate PET/MRI, residual abnormal wall thickening (green arrow) on T2-weighted image (d) and diffusion signal restriction extending to perivesical fat (e - b value 800 s/mm2 trace diffusion weighted image) was presented suggestive of T3 stage. The final cystectomy specimen revealed stage T2, thus the findings of 11C-acetate PET/MRI were considered as true positive for muscle invasion

Fig. 5

Comparison of lymph node staging (N-stage) on pre-transurethral resection (a, b, c) and post-chemotherapy 11C-acetate PET/MRI (d, e, f) in patient number 12, the same patient as in Fig. 4. 17 mm right obturator lymph node (a - white arrow on T2-weighted image) demonstrated increased diffusion signal restriction (b - b value 800 s/mm2 trace diffusion weighted image) and increased 11C-acetate uptake (c - PET fused with T2-weighted image, SUV is scaled from 0.0 to 3.5) suggestive of lymph node metastasis. On post-chemotherapy 11C-acetate PET/MRI, lymph node decreased in size and measured 4 mm (d - green arrow on T2-weighted image) with increased diffusion signal (e - b value 800 s/mm2 trace diffusion weighted image) and increased 11C-acetate uptake (f - PET fused with T2-weighted image, SUV is scaled from 0.0 to 3.0). SUVmax values of the lymph node on the pre-transurethral resection (c) and post-chemotherapy 11C-acetate PET/MRI (f) were 3.4 and 2.8, respectively. The lymph node was confirmed to be lymph node metastasis measuring 3 mm on extended pelvic lymph node dissection, thus the findings of 11C-acetate PET/MRI were considered as true positive

Fig. 6

Comparison of lymph node staging (N-stage) on pre-transurethral resection (a, b, c) and post-chemotherapy 11C-acetate PET/MRI (d, e, f) in a 66-year-old male (patient number 6 in primary imaging). 8 mm retroaortic lymph node (d - white arrow on T2-weighted image) demonstrated increased diffusion signal restriction (b - b value 800 s/mm2 trace diffusion weighted image), and increased 11C-acetate uptake (c - PET fused with T2-weighted image, SUV is scaled from 0.0 to 2.8) suggestive of lymph node metastasis. On post-chemotherapy 11C-acetate PET/MRI, lymph did not decrease in size and measured 7 mm (d - green arrow on T2-weighted image) with increased diffusion signal (e - b value 800 s/mm2 trace diffusion weighted image) and increased 11C-acetate uptake (f - PET fused with T2-weighted image, SUV is scaled from 0.0 to 2.8). SUVmax values of the lymph node on the pre-transurethral resection (c) and post-chemotherapy 11C-acetate PET/MRI (f) was 1.7, 1.3, respectively. No lymph node metastases were found on extended pelvic lymph node dissection, thus the findings of 11C-acetate PET/MRI were considered as false positive