Original Study
Pelvic Lymph Node Staging by Combined 18F-FDG-PET/CT Imaging in Bladder Cancer Prior to Radical Cystectomy

https://doi.org/10.1016/j.clgc.2016.08.009Get rights and content

Abstract

Background

Accurate lymph node (LN) staging in bladder cancer before radical cystectomy is essential as LN metastases have an independent prognostic value. Most studies used a cutoff of > 10 mm in detecting pelvic LN spread. The aim of this study was to evaluate the diagnostic accuracy of contrast-enhanced computed tomography (CT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) alone, or combined for preoperative pelvic LN staging.

Patients and Methods

We retrospectively analyzed the data of 70 bladder cancer patients that were staged with 18F-FDG-PET/CT before radical cystectomy between 2012 and 2015. 18F-FDG-PET images were analyzed visually and semi-quantitatively by calculating the maximum standardized uptake value. CT scans were reviewed using different cutoffs of pelvic LNs, with the best cutoff at 8 mm (area under the curve = 0.684).

Results

Metastatic LNs were confirmed in 53 (2.8%) of 1906 resected LNs in 11 (15.7%) patients. Sensitivity, specificity, and accuracy were 54.5%, 89.8%, and 84.3% for 18F-FDG-PET alone; 45.5%, 91.5%, and 84.3% for CT (LNs > 8 mm) alone; and 27.3%, 96.6%, and 85.7% for CT (LNs > 10 mm) alone, respectively. Combined 18F-FDG-PET/CT resulted in a nonsignificant increase of diagnostic accuracy using a cutoff > 8 mm for LN evaluation (63.6%, 86.4%, and 82.9%, respectively). A significant improvement of sensitivity to 63.6% was achieved only when LNs > 10 mm were considered suspicious (P = .046), but this reduced specificity to 88.1% (P = .025).

Conclusions

Combined 18F-FDG-PET/CT does not seem to be justified in preoperative staging if the threshold of pelvic LNs is set > 8 mm.

Introduction

Radical cystectomy (RC) with extended pelvic lymph node (LN) dissection is recommended as the standard therapy in patients with localized muscle-invasive bladder cancer (MIBC), Bacillus Calmette-Guerin-refractory high-risk non–muscle-invasive bladder cancer (NMIBC), or NMIBC at highest risk of tumor progression.1 However, despite negative local staging, 25% to 30% of patients present with occult pelvic LN metastases at the time of surgery.2, 3, 4 This fact is crucial, as positive LN status is one of the most important predictors for poor oncologic outcome.5, 6 Therefore, accurate preoperative staging is essential, changing treatment strategy in those patients with metastatic spread.7 However, the diagnostic accuracy of standard imaging methods remains low, with controversial results. One explanation can be seen in the discrepancy between the defined threshold of pelvic LN size regarded as pathologically enlarged. Whereas sensitivity ranged only between 9.1% and 29.4% for computed tomography (CT) (LNs > 10 mm) in detecting pelvic LN metastases,8, 9 an increase of sensitivity up to 46% could be achieved by cutoff values > 8 mm.10 Another point is the inability to identify metastases in normal-sized pelvic LNs. Between 29.4% and 68% of false-negative pelvic LNs on standard imaging were micrometastasis < 5 mm on histopathology.11, 12 A recently published study also confirmed that LNs between 6 and 10 mm on preoperative CT were associated with a significantly worse prognosis and higher risk of death after RC.13

Over the last few years, positron emission tomography (PET) is thought to have a diagnostic and prognostic impact in urologic oncology.14, 15 As 18F-fluorodeoxyglucose (18F-FDG) is not a useful tracer for primary bladder cancer detection, owing to its high renal excretion, trials investigated its role in pelvic LN staging, but with very disappointing results.10, 14, 15 Therefore, 18F-FDG-PET is still not recommended in routine LN staging of bladder cancer by the European Association of Urology guidelines.1

The aim of this study was to evaluate if dual imaging by 18F-FDG-PET/CT would increase the diagnostic accuracy in identifying pelvic LN spread in bladder cancer before RC compared with CT alone, using different cutoffs of pelvic LN size.

Section snippets

Materials and Methods

This study was performed according to the principles of the Declaration of Helsinki and its subsequent amendments.16 After approval by the local ethics committee (study number AN2015-0085; 348/4.10), medical records of patients with localized MIBC or recurrent, high-risk NMIBC undergoing preoperative staging by 18F-FDG-PET/CT prior to RC between September 2012 and August 2015 were reviewed retrospectively. The mean time interval between imaging and RC was 21.4 days (range, 14-34 days). Patients

Results

Descriptive and histopathologic characteristics of patients are summarized in Table 1. A total of 70 patients (53 male, 17 female) with a mean age of 69.3 years (range, 38-82 years) fulfilled the inclusion criteria. Orthotopic studer ileal neobladder, ileal conduit, and continent cutaneous catheterizable navel pouch was performed in 30 patients (42.9%), 39 patients (55.7%) and 1 patient (1.4%), respectively. Age (mean ± SD) was significantly lower in patients with orthotopic urinary diversion

Discussion

The current standard imaging methods have similar diagnostic accuracy in detecting pelvic LN metastases ranging from 54% to 97% for CT, and 73% to 98% for magnetic resonance imaging (MRI).18 A more accurate LN staging before cystectomy would be helpful in identifying those patients with metastatic disease, changing treatment plans in up to 27% (18F-FDG-PET/CT) with the possibility to reduce the number of RCs in patients where disease has spread beyond cure.19 Another advantage would be to

Conclusions

We may recommend an additional 18F-FDG-PET imaging in the routine preoperative LN staging in bladder cancer patients before cystectomy, if the threshold of positive pelvic LNs at CT evaluation is set on 10 mm. However, using the best validated cutoff of 8 mm, 18F-FDG-PET in addition to CT does not significantly improve the diagnostic accuracy in detecting pelvic LN metastases and can thus be avoided.

Disclosure

The authors have stated that they have no conflicts of interest.

Acknowledgment

The authors thank Hannes Steiner and Lorraine Burdett for their support and helpful contribution to this work.

References (36)

  • M. Triantafyllou et al.

    Ultrasmall superparamagnetic particles of iron oxide allow for the detection of metastases in normal sized pelvic lymph nodes of patients with bladder and/or prostate cancer

    Eur J Cancer

    (2013)
  • H.C. Thoeny et al.

    Combined ultrasmall superparamagnetic particles of iron oxide-enhanced and diffusion-weighted magnetic resonance imaging reliably detect pelvic lymph node metastases in normal-sized nodes of bladder and prostate cancer patients

    Eur Urol

    (2009)
  • T. Maurer et al.

    Diagnostic efficacy of [11C]choline positron emission tomography/computed tomography compared with conventional computed tomography in lymph node staging of patients with bladder cancer prior to radical cystectomy

    Eur Urol

    (2012)
  • L.S. Mertens et al.

    Occult lymph node metastases in patients with carcinoma invading bladder muscle: incidence after neoadjuvant chemotherapy and cystectomy vs after cystectomy alone

    BJU Int

    (2014)
  • C. Wiesner et al.

    Cancer-specific survival after radical cystectomy and standardized extended lymphadenectomy for node-positive bladder cancer: prediction by lymph node positivity and density

    BJU Int

    (2009)
  • O. Ugurlu et al.

    Does skip metastasis or other lymph node parameters have additional effects on survival of patients undergoing radical cystectomy for bladder cancer?

    Korean J Urol

    (2015)
  • M. Hitier-Berthault et al.

    18 F-fluorodeoxyglucose positron emission tomography-computed tomography for preoperative lymph node staging in patients undergoing radical cystectomy for bladder cancer: a prospective study

    Int J Urol

    (2013)
  • I.G. Jeong et al.

    FDG PET-CT for lymph node staging of bladder cancer: a prospective study of patients with extended pelvic lymphadenectomy

    Ann Surg Oncol

    (2015)
  • Cited by (41)

    • The increasing indications of FDG-PET/CT in the staging and management of Invasive Bladder Cancer

      2022, Urologic Oncology: Seminars and Original Investigations
      Citation Excerpt :

      Initial concerns around the high urinary excretion of 18F-FDG in the bladder and ureters (which can mask bladder lesions and regional metastatic lymph nodes), and substantial overlap of the standardized uptake values (SUVs) from the active inflammatory process and the malignant lesion has limited its use. This is exemplified by small sample studies which have suggested that FDG/PET CT does not confer the appropriate diagnostic accuracy required for the identification of regional lymph node metastasis [29,30]. To overcome these limitations, simple, non-invasive protocols have been proposed.

    • PET/CT in Bladder Cancer: An Update

      2022, Seminars in Nuclear Medicine
      Citation Excerpt :

      In BC patients, metastases often involve LN, causing little of any enlargement of the LN, resulting in high false-negative rates reported for both CT and MR.34 For LNM evaluation, accuracy of CT ranges from 73% – 92%, and for MR 73% – 90%.35 Consequently, several studies have evaluated the role of FDG PET/CT for detection of LNM.11,17,21,36-54 The reported sensitivities range from 23% – 100%, and the specificities range from 33% – 100%.

    • PET imaging in renal and bladder cancers

      2022, Nuclear Medicine and Molecular Imaging: Volume 1-4
    • Diagnosis and Staging of Bladder Cancer

      2021, Hematology/Oncology Clinics of North America
      Citation Excerpt :

      PET with 18F-fluoro-d-glucose is not currently recommended for local staging of BCa because of the excretion of radiotracer into the bladder. However, evidence supports its potential role in other settings: PET/CT could improve detection of involved nodes that are still not considered abnormal by size criteria.27 Also, it could potentially be used to assess any other sites of metastasis when surgical resection is being considered for oligometastatic disease.28

    • Preoperative chemotherapy in clinically node positive muscle invasive bladder cancer: Radiologic variables can predict response

      2021, Urologic Oncology: Seminars and Original Investigations
      Citation Excerpt :

      evaluated various node size cut-offs, which ranged from 6.8 mm to 10 mm. Their study commented on an increase from 8 mm to 10 mm as a cut-off that did not increase specificity, but decreased sensitivity twofold [28]. In a study by Schmid et al., lymph nodes between 5 mm and 10 mm, usually classified as nonpathologic, were associated with a significantly worse prognosis.

    View all citing articles on Scopus
    View full text