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Sinha, A. Sentinel Lymph Node Detection in Urinary Bladder Cancer. Encyclopedia. Available online: https://encyclopedia.pub/entry/20485 (accessed on 17 June 2025).
Sinha A. Sentinel Lymph Node Detection in Urinary Bladder Cancer. Encyclopedia. Available at: https://encyclopedia.pub/entry/20485. Accessed June 17, 2025.
Sinha, Ankit. "Sentinel Lymph Node Detection in Urinary Bladder Cancer" Encyclopedia, https://encyclopedia.pub/entry/20485 (accessed June 17, 2025).
Sinha, A. (2022, March 11). Sentinel Lymph Node Detection in Urinary Bladder Cancer. In Encyclopedia. https://encyclopedia.pub/entry/20485
Sinha, Ankit. "Sentinel Lymph Node Detection in Urinary Bladder Cancer." Encyclopedia. Web. 11 March, 2022.
Sentinel Lymph Node Detection in Urinary Bladder Cancer
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This entry is adapted from the peer-reviewed paper 10.3390/curroncol29030114

Detection of lymph node status in bladder cancer significantly impacts clinical decisions regarding its management. There is a wide range of detection modalities for this task, including lymphoscintigraphy, computed tomography, magnetic resonance imaging, single-photon emission computed tomography, positron emission tomography, and fluoroscopy.

bladder cancer sentinel lymph nodes detection imaging PLND

1. Introduction

Bladder cancer is the fourth most common cancer in men and the tenth most common in women. It has the highest lifetime cost per patient of all cancer types due to the long-term survival rate and intensive surveillance that is used [1]. Locally advanced disease is optimally managed with radical cystectomy and urinary diversion, which is associated with the worst health-related quality of life among all cancer patients [2][3].
Muscle invasive bladder cancer (MIBC) has a mortality rate of 50% over 5 years despite optimal management and no histopathologic signs of lymph node metastases [4][5]. This suggests half of patients have disease dissemination that is not detected by current staging techniques [6][7]. As lymph node metastases are associated with negative prognosis, radical cystectomy is routinely combined with lymphadenectomy as routine management of MIBC [5][6][8][9]. The extent of lymph node dissection is a highly debated topic, as it represents a fine balance between minimising disease spread with longer surgeries and complications, such as bleeding and lymphocoele development [8].
Although lymph node biopsy is pertinent in bladder cancer, the current templates of limited, standard, extended, and super extended pelvic lymph node dissection (PLND) could be improved through the use of lymph node mapping. This can aid selective resection of invaded LNs similar to the techniques used in breast and melanoma tumours [8]. An important aspect of LN mapping is detection of sentinel lymph nodes (SLNs) to assess nodal disease status. SLNs are thought to be the first draining lymph nodes from the cancer site and therefore reflect the pathologic status of the remaining lymphatic region. SLN biopsy has been shown to be a useful step in evaluating disease spread in melanoma, penile, and breast cancer [9][10].

2. Lymphoscintigraphy

Lymphoscintigraphy is the detection of the gamma (y) radiation given off by radioactive tracers that are injected into the body. It is performed preoperatively to inform surgical lymph node dissection. The most commonly used radiotracer is 99mTechnetium, used to label a colloid, such as a sulphur compound or albumin. 99mTc is used as it is less irradiating than some of the early tracers developed (such as 198Au) [11]. These were initially detected by planar gamma (y) cameras but this was shown to have a low detection rate of only 23% of patients by Liedberg et al. in their pilot study of 75 patients [12]. Reasons for this could include extensive metastasis obstructing the passage of lymph in the vessels (therefore, preventing the tracer reaching further downstream or forcing it to go to the contralateral side), and radioactive interference from the primary injection, site preventing nearby “hot spots” to be discerned (the “shine-through effect”).
Despite the benefits of preoperative lymphatic visualisation and SLN localisation, there are difficulties with low detection rates. Additionally, the general limitations of radiotracer use (radiation exposure, limited radiotracer availability, high costs, the "shine through" effect, long preparation times, and limited half-life of 99mTc (6 h)) prevent planar lymphoscintigraphy replacing current pre- or intraoperative modalities.

3. Computed Tomography (CT)/Single-Photon Emission Computer Tomography (SPECT)

Lymphadenectomy and histology are widely regarded as the most accurate methods for detecting metastatic deposits in lymph nodes. However, their association with morbidity—and, rarely, mortality—resulted in CT being explored as one of the first alternatives to evaluating and staging bladder cancer [13]. CT and MRI are now routinely utilised to stage advanced disease in candidates for radical cystectomy [14].
The initial use of CT showed low sensitivity and a high false-negative rate as it relied on visibly enlarged lymph nodes to detect disease spread. Of note, there are benign causes of enlarged lymph nodes, and the internal architecture of the nodes could not be discerned. The node itself may also be lost between the “slices” depending on its size [13][15]. Paik et al. reported CT resulted in accurate staging of 54.9% of LNs, with 39% under-staging and 6.1% over-staging [16].
Single-photon emission computer tomography (SPECT) is an imaging modality that uses radiotracers similarly to other methods mentioned above, but images the radiation given off with a gantry of y-cameras, using software to then create a 3D map of radiation hot spots. Studies combining CT with SPECT have the anatomical benefits of CT with the functional benefits of lymphoscintigraphy imaging [17].
The benefits of this technique were demonstrated by Polom et al., who compared these methods in a study of 38 patients with N0 staging according to CT/MRI [18]. The method involved injecting 99mTc-nanocolloid peritumourly via cystoscopy, then Hybrid SPECT/CT was performed 3–8 h later. This technetium tracer is a nanoparticle of radioactive 99mTc, releasing y radiation. Preoperative SPECT/CT has repeatedly been shown to significantly impact surgical approach. Polom et al. found using SPECT/CT altered surgical approach in 7.8% of cases to include resection of lymph nodes outside the PLND template. This method is also effective in melanoma, prostate, cervical, and endometrial cancers [19][20][21][22].

4. Positron Emission Tomography (PET)

Positron Emission Tomography (PET) scans use radioactive tracers to create 3D images similar to SPECT, but where SPECT uses tracers that release gamma rays, PET uses tracers that produce positrons which interact with local electrons in the body, releasing energy through photons, which are then detected [17]. The tracer used for this modality is 18F-fluorodeoxyglucose (FDG), meaning the scan is often referred to as FDG-PET. This glucose analogue differentiates PET from other imaging modalities, as the FDG acts as a proxy for the metabolism of glucose in the body, meaning PET allows functional imaging rather than structural imaging. Its utility in oncology is widely recognised due to the increased metabolic demand of neoplastic cells causing increased FDG uptake to these areas [23]. This also means that PET can potentially identify metastases in normal sized lymph nodes as it is not reliant on structural changes, unlike conventional CT/MRI. The main use of FDG-PET may be in evaluating lymph nodes deemed suspicious by CT/MRI. This is shown by Dason et al., who studied routine preoperative use of FDG-PET in 185 patients, and found a sensitivity of 92% and a specificity of 91% among 51 suspicious LNs [24]. This combined use of PET and CT/MRI can effectively rule out suspicious LNs. However, they also found low sensitivities (7–23%) in patients found to be N0 on CT. This is likely due to the low burden of disease with smaller median metastasis diameters, meaning less metabolic requirement and FDG uptake. As such, Dason et al. recommended that FDG-PET should not be used routinely in candidates for radical cystectomy, particularly if they lack clinically suspicious lymph nodes [24].

5. Magnetic Resonance Imaging (MRI)

MRI works by using powerful magnets to detect energy released from proton spin displacement to discern between types of tissue [25]. MRI is another imaging modality which requires changes in lymph node size or aberrant contrast enhancement to detect disease spread. As a result, it generally shows similar results to CT, as both modalities rely on lymph node morphology [15]. Although both CT and MRI are routinely used to stage disease in candidates for radical cystectomy, MRI has been shown to have a higher summary sensitivity—60% (CT—40%) [14]. Methods to address its weaknesses include using diffusion-weighted MRI (DW-MRI) and the use of ultra-small, superparamagnetic particles of iron oxide (USPIO) nanoparticles.
DW-MRI studies the random thermal motion of water molecules in the form of an apparent diffusion coefficient (ADC). The random diffusion of water is generally more restricted in neoplastic tissues than normal tissue due to the higher cell density and the abundance of intra- and extracellular membranes. Therefore, neoplastic tissues have lower ADCs than that of regular tissue. Papalia et al. showed the ADC of metastatic lymph nodes was significantly lower than that of regular lymph nodes [15]. The ADC represents an advantage over CT, and conventional MRI as it is not associated with lesion size. However, DW-MRI does have its own limits. ADC depends on many variables, such as body temperature, tissue pressure, perfusion rate, and magnetic environment, and the interpretation is operator-dependent [15].

6. Indocyanine Green (ICG) Near Infrared (NIR) Fluorescence

Optical imaging using near-infrared (NIR) fluorescence has emerged recently as a safe, real-time method of identifying lymph nodes intraoperatively. It uses intravenous injection of a fluorescent dye indocyanine green (ICG), which has a peak absorption in the NIR wavelength range (820 nm). This means it can be detected by these NIR waves at depths of 5–10 mm in tissues [26]. As the NIR spectrum is also outside visible light, it does not affect the surgical field. ICG’s half-life within the body is around 3–4 min and is excreted by the liver [26].
This technique has already enjoyed some success in identifying SLNs, with Jewell et al. identifying 95% of SLNs in their trial of 227 patients with uterine and cervical cancers by injecting ICG intracervically [27], and Schaafsma et al. achieving a 92% detection rate in patients with high grade bladder cancer when appropriately distending the bladder to maximise lymph drainage [28].

References

  1. Tomlinson, B.; Lin, T.Y.; Dall’Era, M.; Pan, C.X. Nanotechnology in bladder cancer: Current state of development and clinical practice. Nanomedicine 2015, 10, 1189.
  2. Avis, N.E.; Smith, K.W.; McGraw, S.; Smith, R.G.; Petronis, V.M.; Carver, C.S. Assessing quality of life in adult cancer survivors (QLACS). Qual. Life Res. 2005, 14, 1007–1023.
  3. Avis, N.E.; Deimling, G.T. Cancer survivorship and aging. Cancer 2008, 113, 3519–3529.
  4. Sherif, A.; Garske, U.; de La Torre, M.; Thörn, M. Hybrid SPECT-CT: An Additional Technique for Sentinel Node Detection of Patients with Invasive Bladder Cancer. Eur. Urol. 2006, 50, 83–91.
  5. Bassi, P.; Ferrante, G.D.; Piazza, N.; Spinadin, R.; Carando, R.; Pappagallo, G.; Pagano, F. Prognostic factors of outcome after radical cystectomy for bladder cancer: A retrospective study of a homogeneous patient cohort. J. Urol. 1999, 161, 1494–1497.
  6. Aljabery, F.; Shabo, I.; Olsson, H.; Gimm, O.; Jahnson, S. Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer: A prospective clinical study. BJU Int. 2017, 120, 329–336.
  7. Dorin, R.P.; Daneshmand, S.; Eisenberg, M.S.; Chandrasoma, S.; Cai, J.; Miranda, G.; Nichols, P.W.; Skinner, D.G.; Skinner, E.C. Lymph node dissection technique is more important than lymph node count in identifying nodal metastases in radical cystectomy patients: A comparative mapping study. Eur. Urol. 2011, 60, 946–952.
  8. Liss, M.A.; Noguchi, J.; Lee, H.J.; Vera, D.R.; Kader, A.K. Sentinel lymph node biopsy in bladder cancer: Systematic review and technology update. Indian J. Urol. 2015, 31, 170–175.
  9. Cabanas, R. An approach for the treatment of penile carcinoma. Cancer 1977, 39, 456–466.
  10. Tanis, P.J.; Nieweg, O.E.; Valdés Olmos, R.A.; Rutgers, E.J.T.; Kroon, B.B.R. History of sentinel node and validation of the technique. Breast Cancer Res. 2001, 3, 109–112.
  11. International Atomic Energy Agency. Radiopharmaceuticals for Sentinel Lymph Node Detection: Status and Trends; International Atomic Energy Agency: Vienna, Austria, 2015.
  12. Liedberg, F.; Chebil, G.; Davidsson, T.; Gudjonsson, S.; Månsson, W. Intraoperative sentinel node detection improves nodal staging in invasive bladder cancer. J. Urol. 2006, 175, 84–88.
  13. Salo, J.O.; Kivisaari, L.; Rannikko, S.; Lehtonen, T. The value of CT in detecting pelvic lymph node metastases in cases of bladder and prostate carcinoma. Scand. J. Urol. Nephrol. 1986, 20, 261–265.
  14. Crozier, J.; Papa, N.; Perera, M.; Ngo, B.; Bolton, D.; Sengupta, S.; Lawrentschuk, N. Comparative sensitivity and specificity of imaging modalities in staging bladder cancer prior to radical cystectomy: A systematic review and meta-analysis. World J. Urol. 2019, 37, 667–690.
  15. Papalia, R.; Simone, G.; Grasso, R.; Augelli, R.; Faiella, E.; Guaglianone, S.; Cazzato, R.; Del Vescovo, R.; Ferriero, M.; Zobel, B.; et al. Diffusion-weighted magnetic resonance imaging in patients selected for radical cystectomy: Detection rate of pelvic lymph node metastases. BJU Int. 2012, 109, 1031–1036.
  16. Paik, M.L.; Scolieri, M.J.; Brown, S.L.; Spirnak, J.P.; Resnick, M.I. Limitations of computerized tomography in staging invasive bladder cancer before radical cystectomy. J. Urol. 2000, 163, 1693–1696.
  17. Nuclear Medicine. Available online: https://www.nibib.nih.gov/science-education/science-topics/nuclear-medicine (accessed on 8 December 2021).
  18. Połom, W.; Markuszewski, M.; Cytawa, W.; Lass, P.; Matuszewski, M. Radio-guided lymph node mapping in bladder cancer using SPECT/CT and intraoperative γ-probe methods. Clin. Nucl. Med. 2016, 41, e362–e367.
  19. Veenstra, H.J.; Klop, W.M.C.; Speijers, M.J.; Lohuis, P.J.F.M.; Nieweg, O.E.; Hoekstra, H.J.; Balm, A.J.M. Lymphatic drainage patterns from melanomas on the shoulder or upper trunk to cervical lymph nodes and implications for the extent of neck dissection. Ann. Surg. Oncol. 2012, 19, 3906–3912.
  20. Vermeeren, L.; Valdés Olmos, R.A.; Meinhardt, W.; Bex, A.; Van Der Poel, H.G.; Vogel, W.V.; Sivro, F.; Hoefnagel, C.A.; Horenblas, S. Value of SPECT/CT for detection and anatomic localization of sentinel lymph nodes before laparoscopic sentinel node lymphadenectomy in prostate carcinoma. J. Nucl. Med. 2009, 50, 865–870.
  21. Sawicki, S.; Kobierski, J.; Łapińska-Szumczyk, S.; Lass, P.; Cytawa, W.; Bianek-Bodzak, A.; Wydra, D. Comparison of SPECT-CT results and intraoperative detection of sentinel lymph nodes in endometrial cancer. Nucl. Med. Commun. 2013, 34, 590–596.
  22. Wydra, D.; Sawicki, S.; Wojtylak, S.; Bandurski, T.; Emerich, J. Sentinel node identification in cervical cancer patients undergoing transperitoneal radical hysterectomy: A study of 100 cases. Int. J. Gynecol. Cancer 2006, 16, 649–654.
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  27. Jewell, E.L.; Huang, J.J.; Abu-Rustum, N.R.; Gardner, G.J.; Brown, C.L.; Sonoda, Y.; Barakat, R.R.; Levine, D.A.; Leitao, M.M. Detection of sentinel lymph nodes in minimally invasive surgery using indocyanine green and near-infrared fluorescence imaging for uterine and cervical malignancies. Gynecol. Oncol. 2014, 133, 274–277.
  28. Schaafsma, B.E.; Verbeek, F.P.R.; Elzevier, H.W.; Tummers, Q.R.J.G.; Van Der Vorst, J.R.; Frangioni, J.V.; Van De Velde, C.J.H.; Pelger, R.C.M.; Vahrmeijer, A.L. Optimization of Sentinel Lymph Node Mapping in Bladder Cancer using Near-Infrared Fluorescence Imaging. J. Surg. Oncol. 2014, 110, 845.
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Subjects: Urology & Nephrology
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