Sentinel Lymph Node Imaging in Urologic Oncology

Sherif Mehralivand; Henk van der Poel; Alexander Winter; Peter L. Choyke; Peter A. Pinto; Baris Turkbey

Disclosures

Transl Androl Urol. 2018;7(5):887-902. 

In This Article

Abstract and Introduction

Abstract

Lymph node (LN) metastases in urological malignancies correlate with poor oncological outcomes. Accurate LN staging is of great importance since patients can benefit from an optimal staging, accordingly aligned therapy and more radical treatments. Current conventional cross-sectional imaging modalities [e.g., computed tomography (CT) and magnetic resonance imaging (MRI)] are not accurate enough to reliably detect early LN metastases as they rely on size criteria. Radical lymphadenectomy, the surgical removal of regional LNs, is the gold standard of invasive LN staging. The LN dissection is guided by anatomic considerations of lymphatic drainage pathways of the primary tumor. Selection of patients for lymphadenectomy heavily relies on preoperative risk stratification and nomograms and, as a result a considerable number of patients unnecessarily undergo invasive staging with associated morbidity. On the other hand, due to individual variability in lymphatic drainage, LN metastases can occur outside of standard lymphadenectomy templates leading to potential understaging and undertreatment. In theory, metastases from the primary tumor need to pass through the chain of LNs, where the initial node is defined as the sentinel LN. In theory, identifying and removing this LN could lead to accurate assessment of metastatic status. Radiotracers and more recently fluorescent dyes and superparamagnetic iron oxide nanoparticles (SPION) are injected into the primary tumor or peritumoral and the sentinel LNs are identified intraoperatively by a gamma probe, fluorescent camera or a handheld magnetometer. Preoperative imaging [e.g., single-photon emission computed tomography (SPECT)/CT or MRI] after tracer injection can further improve preoperative planning of LN dissection. While sentinel LN biopsy is an accepted and widely used approach in melanoma and breast cancer staging, its use in urological malignancies is still limited. Most data published so far is in penile cancer staging since this cancer has a typical echelon-based lymphatic metastasizing pattern. More recent data is encouraging with low false-negative rates, but its use is limited to centers with high expertise. Current guidelines recommend sentinel LN biopsy as an accepted alternative to modified inguinal lymphadenectomy in patients with pT1G2 disease and non-palpable inguinal LNs. In prostate cancer, a high diagnostic accuracy could be demonstrated for the sentinel approach. Nevertheless, due to lack of data or high false-negative rates in other urological malignancies, sentinel LN biopsy is still considered experimental in other urological malignancies. More high-level evidence and longitudinal data is needed to determine its final value in those malignancies. In this manuscript, we will review sentinel node imaging for urologic malignancies.

Introduction

Most urological malignancies metastasize through the lymphatic system before spreading to other organ systems. The presence of LN metastases is associated with poor oncological outcomes and often requires more radical treatment regimens with neoadjuvant and adjuvant treatment strategies in addition to removal of the primary tumor. The gold standard in LN staging is lymphadenectomy, surgical removal of LNs with ensuing histopathological examination. With this invasive approach even microscopic metastases can be detected. The decision to perform a lymphadenectomy is based on the theoretical risk for LN metastases and is usually estimated by local tumor stage, clinical parameters, serum or urine biomarkers and imaging findings. LNs are then removed systematically based on standardized templates from predefined anatomic regions of lymphatic drainage. However, this is associated with significant morbidity due to surgical and postoperative complications. Furthermore, a significant number of LN metastases can occur outside the surgical template. Thus, there is a growing demand for tumor-specific imaging tools to identify LN metastases before or during surgery.

The most common imaging studies used in nodal staging in urologic oncology are computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET)/CT or PET/MRI. CT and MRI are based on the detection of nodes beyond a certain size, typically 8–10 mm, and the shape of LNs (spherical vs. elongated). Although larger LNs and round shape are associated with metastases these findings often lack diagnostic accuracy. Small and microscopic LN involvement remains undetectable on CT and MRI as they neither enlarge the node nor distort its shape. Enlarged LNs on the other hand can also be caused by other etiologies than cancer e.g., inflammation or reactive changes after surgical or medical treatment. A novel approach in the search for more cancer-specific staging techniques is PET/CT imaging with tumor-specific radioactive tracers.[1] Nevertheless, even these modalities are subject to detection limits and false negative results.

Direct visualization of LN metastases could enable a more tailored approach improving assessment of LN involvement and decreasing morbidity at the same time. Sentinel LN surgery is an invasive staging approach based on the premise that cancer metastases must pass through one gatekeeper LN or group of LNs before spreading further through the body.[2–5] Injection of a fluorescent, gamma-emitting radioactive or superparamagnetic tracer into the primary tumor or peritumoral area leads to uptake of tracer material in sentinel LNs. These LNs can then be identified either by a fluorescence or gamma camera/probe or a handheld magnetometer during surgery. Preoperative hybrid single-photon emission computed tomography (SPECT)/CT or MRI can further improve visualization and preoperative planning. In breast cancer and melanoma, this approach has become an accepted and widely used procedure for staging and risk assessment and appears to improve melanoma-specific survival.[6–8] More recently, the technique is being investigated in urological malignancies. This manuscript provides an overview of the basic principles, techniques and reported outcomes of sentinel LN surgery in urological malignancies and discusses future potentials and limitations.

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