Hybrid Indocyanine Green-99mTc-nanocolloid for Single-photon Emission Computed Tomography and Combined Radio- and Fluorescence-guided Sentinel Node Biopsy in Penile Cancer: Results of Inguinal Basins Assessement at a Single Institution - Beyond the Abstra

The presence of lymph node metastasis in penile cancer is the main predictor of 5-year cancer-specific survival, which drops rapidly from 96% for pN0 patients to 37% for pN3 patients with pelvic lymph node metastasis or extranodal extension.1 As the delayed treatment of lymph node metastasis has a worse prognosis and the gold standard inguinal lymph node dissection (ILND) is burdened with high morbidity rates, our group introduced dynamic sentinel node biopsy (DSNB) for penile cancer in 1994.2 Over the years, several enhancements to the traditional approach have made DSNB for penile cancer into the reliable procedure it is today.3

The most recent enhancement has been the introduction of the hybrid tracer Indocyanine Green (ICG)-99mTc-nanocolloid for Single-photon Emission Computed Tomography (SPECT/CT) and intraoperative radio and fluorescence guidance.4 The addition of SPECT/CT to standard scintigraphy improves preoperative sentiel node (SN) identification with its increased sensitivity and the addition of the third dimension. Intraoperatively, fluorescence imaging of ICG leads to a significantly higher (optical) SN visualization rate compared to the traditionally used blue dye. Nevertheless, due to the limited tissue penetration depth of the fluorescent signal compared to the radioactive signal, the combined use of radio guidance intraoperatively remains indispensable.

In this article, we present our nearly 10 years of experience with the hybrid tracer and SPECT/CT for DSNB of penile cancer. The tracer has been developed by the Interventional Molecular Imaging Laboratory at the Leiden University Medical Center, led by Prof. Fijs van Leeuwen. It is interesting to note that back then, dr. Oscar Brouwer, who is currently the senior author (and successor of Prof. Horenblas), worked as a PhD student and wrote his thesis on the introduction of the tracer and initiated the first prospective study with ICG-99mTc-nanocolloid in 2011.5,6 From this endeavor, a great collaboration sparked which has been a major driver for this innovations. This alliance and its results have made DSNB as described throughout our manuscript the current standard of care in our institution for lymph node staging in all penile cancer patients with negative palpation, negative ultrasound, and fine-needle aspiration cytology and a primary tumor staging higher or equal to pT1G2.

We hope that these developments and this publication will (re-)ignite the worldwide interest for the use of DSNB in penile cancer patients. While we are aware that the logistics, costs, and materials needed for DSNB might encompass more than performing traditional ILND, we believe the lower complication rates and added patient quality of life are worth it. We firmly believe we can only move forward by collaborating, especially in rare diseases such as penile cancer. Therefore, we hope that the DSNB technique is adopted in more centers, and invite interested urologists to contact us and visit Amsterdam to learn the procedure at our center.

Written by: Hielke-Martijn de Vries, PhD Candidate in Urology, and Oscar Brouwer, MD, PhD, FEBU, Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands

References:

  1. Djajadiningrat, Rosa S., Niels M. Graafland, Erik van Werkhoven, Wim Meinhardt, Axel Bex, Henk G. van der Poel, Hester H. van Boven, Renato A. Valdés Olmos, and Simon Horenblas. "Contemporary management of regional nodes in penile cancer—improvement of survival?." The Journal of urology 191, no. 1 (2014): 68-73.
  2. Horenblas, Simon, LIESBETH JANSEN, Willem Meinhardt, Cornelis A. Hoefnagel, D. A. P. H. N. E. de JONG, and OMGO E. NIEWEG. "Detection of occult metastasis in squamous cell carcinoma of the penis using a dynamic sentinel node procedure." The Journal of urology 163, no. 1 (2000): 100-104.
  3. Wever, Lieke, Hielke-Martijn de Vries, Henk van der Poel, Fijs van Leeuwen, Simon Horenblas, and Oscar Brouwer. "Minimally invasive evaluation of the clinically negative inguinal node in penile cancer: Dynamic sentinel node biopsy." In Urologic Oncology: Seminars and Original Investigations. Elsevier, 2020.
  4. Dell’Oglio, Paolo, Hielke M. de Vries, Elio Mazzone, Gijs H. KleinJan, Maarten L. Donswijk, Henk G. van der Poel, Simon Horenblas, Fijs WB van Leeuwen, and Oscar R. Brouwer. "Hybrid Indocyanine Green–99mTc-nanocolloid for Single-photon Emission Computed Tomography and Combined Radio-and Fluorescence-guided Sentinel Node Biopsy in Penile Cancer: Results of 740 Inguinal Basins Assessed at a Single Institution." European Urology (2020).
  5. Brouwer, Oscar R., Tessa Buckle, Lenka Vermeeren, W. Martin C. Klop, Alfons JM Balm, Henk G. van der Poel, Bas W. van Rhijn et al. "Comparing the hybrid fluorescent–radioactive tracer indocyanine green–99mTc-nanocolloid with 99mTc-nanocolloid for sentinel node identification: a validation study using lymphoscintigraphy and SPECT/CT." Journal of Nuclear Medicine 53, no. 7 (2012): 1034-1040.
  6. Brouwer, Oscar R., Nynke S. van den Berg, Hanna M. Mathéron, Thomas Wendler, Henk G. van der Poel, Simon Horenblas, Renato A. Valdés Olmos, and Fijs WB van Leeuwen. "Feasibility of intraoperative navigation to the sentinel node in the groin using preoperatively acquired single photon emission computerized tomography data: transferring functional imaging to the operating room." The Journal of urology 192, no. 6 (2014): 1810-1816.
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