Original article
Final analysis of a prospective trial on functional imaging for nodal staging in patients with prostate cancer at high risk for lymph node involvement,☆☆

https://doi.org/10.1016/j.urolonc.2014.11.008Get rights and content

Abstract

Purpose

Accurate staging modalities to diagnose lymph node involvement in patients with prostate cancer (PCa) are lacking. We wanted to prospectively assess sensitivity, specificity, and positive predictive value (PPV) and negative predictive value of 11C-choline positron emission tomography (PET)-computed tomography (CT) and diffusion-weighted (DW) magnetic resonance imaging (MRI) for nodal staging in patients with PCa at high risk for lymph node involvement.

Material and methods

In total, 75 patients with a risk≥10% but<35% for lymph node (LN) metastases (Partin tables) who had N0 lesions based on the findings of contrast-enhanced CT scans were included. Patients underwent 11C-choline PET-CT and DW MRI before surgery, which consisted of a superextended lymph node dissection followed by radical prostatectomy. LNs were serially sectioned and histopathologically examined after pankeratin staining. These results were used as the gold standard to compare with the imaging results.

Results

Of 1,665 resected LNs (median = 21, range: 7–49), 106 affected LNs (median = 2, range: 1–10) were found in 37 of 75 patients (49%). On a region-based analysis, we found a low sensitivity of 8.2% and 9.5% and a PPV of 50.0% and 40.0% for 11C-choline PET-CT and DW MRI, respectively. The patient-based analysis showed a sensitivity of 18.9% and 36.1% for and a PPV of 63.6% and 86.7% 11C-choline PET-CT and DW MRI, respectively. Even when both imaging modalities were combined, sensitivity values remained too low to be clinically useful.

Conclusions

Because of the low sensitivity, there is no indication for routine clinical use of either 11C-choline PET-CT or DW MRI for LN staging in patients with PCa, in whom CT scan findings were normal.

Introduction

Accurate staging modalities to diagnose lymph node involvement (LNI) in patients with prostate cancer (PCa) are currently lacking. Conventional imaging modalities used for lymph node (LN) evaluation, i.e., contrast-enhanced computed tomography (CT) and T2-weighted magnetic resonance imaging (MRI), rely on size criteria next to other characteristics, such as contrast enhancement, shape, localization, and lack of central (hilar) fat to classify LN [1]. In a meta-analysis from Hövels et al. [2], 24 studies published between 1980 and 2003 were included, demonstrating a pooled sensitivity of approximately 40% for both CT and MRI. This low sensitivity for CT scan was confirmed in a large cohort of contemporary patients by Briganti et al. [3], even in patients at high risk for LNI.

Given these significant limitations, only an extended lymph node dissection ensures a full nodal staging at present [4]. This invasive procedure is, however, associated with a certain risk of complications, and the search for alternative approaches is therefore still warranted [5]. In recent years, promising new functional imaging modalities such as choline positron emission tomography (PET)-CT scan and diffusion-weighted (DW) MRI have been introduced. Carbon-11-labeled choline (11C-choline) is a radiopharmaceutical that is potentially useful for tumor imaging, as it is incorporated in cell membranes of proliferating cells in the form of phosphatidylcholine. As PCa is associated with increased cell proliferation and choline-kinase upregulation, there is evidence that choline can be used to visualize nodal metastases [6]. DW imaging measures the amount of water diffusion in tissue that occurs by applying a pair of strong gradient pulses and can provide information on tissue cellularity and cell membrane integrity. Data on nodal staging for PCa using DW MRI are rare, but encouraging results have been reported in other cancer types [7], [8].

The objective of this study was to prospectively assess the performance of 11C-choline PET-CT and DW MRI for nodal staging in patients at high risk for LNI, using histopathology as the gold standard. We hereby report the final results of a previously published interim analysis on 36 patients [9].

Section snippets

Patients

Between February 2008 and February 2011, 75 consecutive patients with localized, biopsy-proven prostate adenocarcinoma were scheduled for radical prostatectomy (RP) and superextended lymph node dissection (seLND). The primary tumor was staged by digital rectal examination and transrectal ultrasound, a contrast-enhanced CT scan was performed for nodal staging and patients were screened for the presence of bone metastases with bone scintigraphy. Patients younger than 75 years were prospectively

Results

Patient and tumor characteristics are depicted in Table 1. The seLND yielded up to 1,665 LNs with a median of 21 (range: 7–49) nodes per patient. In total, 37 of 75 patients (49%) were found to be node positive (N+) with 106 affected LNs (median = 2, range: 1–10). Affected LNs were located in the internal iliac region (n = 35), the external iliac region (n = 30), the obturator fossa (n = 26), the presacral (n = 9), common iliac (n = 5), and aortic bifurcation region (n = 1). In total, 47 (44%)

Discussion

According to the current guidelines, pelvic lymph node dissection remains the most reliable staging method given the significant limitations of preoperative imaging in the detection of small metastases (<5 mm) [4].

With this study, we aimed at prospectively assessing the role of 2 functional imaging modalities for N staging that enable the visualization of functional features such as cell proliferation (11C-choline PET-CT) and cellularity (DW MRI). The current results confirm those of our

Conclusions

Based on the low sensitivity values obtained for both 11C-choline PET-CT and DW MRI, we conclude that there is no indication for routine clinical use of these functional imaging techniques in the pretreatment workup for LN staging in patients with PCa with negative findings on a CT scan.

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    This work was supported through a research Grant of IWT Belgium, Institute for the Promotion of Innovation by Science and Technology in Flanders IWT TBM 060793, The National Cancer Plan 29, Belgium, and the “Stichting Emmanuel van der Schueren, de wetenschappelijke partner van de Vlaamse Liga tegen Kanker” Belgium.

    ☆☆

    K.H. is a fundamental clinical researcher of the Research Foundation, Flanders (Belgium). S.J., E.L., and C.M.D. are supported by a Grant from the “Klinisch Onderzoeksfonds (KOF)—University Hospitals Leuven.”

    1

    Both authors contributed equally to this manuscript.

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