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Indocyanine Green guided pelvic lymph node dissection in prostate cancer
Posted in Lectures on 2 July 2019

Miguel Ramírez Backhaus. MD. PhD. FEBU.
Associate Professor University CEU. Cardenal Herrera.
Senior Attending Urologist in Fundación IVO. Co-Director of urosalud SLP

Introduction

According to the Swedish National PCA Register, PCA was the most common cause of death among patients with intermediate or high-risk disease 1. One reason potentially explaining this high mortality could be that some of those cases are no longer organ-confined, with the affected patients already harboring occult metastasis at the time of diagnosis. 

Therefore, adding pelvic lymph node dissection to radical prostatectomy may play a critical role in the debulking capacity of surgery in these stages of the disease2

On the other hand, current clinical imaging, including PSMA Ga68, is not sufficiently accurate to detect LNM or systemic disease in the earlier course of the disease, with a representative lymph node (LN) dissection remaining superior to the best imaging tools.

Objectives

To increase the evidence that ICG guided pelvic lymph node dissection is useful to accurately stage the N status of a patient who undergoes radical prostatectomy and that it may improve the quality of the lymphadenectomy, as it describes the anatomy of the prostate gland’s lymphatic drainage.

Methods

We will describe the procedure and go through the updated results of prospective collected data from a single center experience. 

The procedure starts by diluting a dose of 25 mg ICG in 5 ml sterile water solution which will be used for injection. The patient is in a dorsal lithotomy position; trans-rectal ultrasound is used, the transducer should be mounted on a stepping device that allows for the prostate to be scanned. A brachytherapy implant grid mounted on the stepper is placed against the perineum. 2.5 ml of the dilution were injected the middle of the transitional zone in each prostatic lobe. Later the patient was re-positioned, scrubbed and draped for the prostatectomy. 

Surgery starts with the ICG-guided-PLND. ICG-stained-lymph nodes are independently resected and carefully sampled individually. An ex vivo test should be performed, in order to separate the node from the surrounding adipose tissue, and labelled according to a pelvic anatomic scheme. Sometimes, the lymph node vessel is observed driving fluorescence to nodes above the common iliac artery, but the dissection stops at the aorta bifurcation.  After the dissection of the fluorescents nodes, an ePLND should be performed, at least up to the crossing ureter, medial and lateral to the internal iliac artery. Lastly, a radical prostatectomy was conducted. We used a dedicated laparoscopic fluorescence imaging system (D-light P, Karl Storz, Tuttlingen, Germany) 2

All available tissue from ICG-stained-LN should be sliced at 250 μm and each level should be assessed by hematoxylin-eosin and immunohistochemistry staining.  The remaining nodes from the extended LND are usually processed in the usual manner, staining a central tissue slide. 2

Results

With this technique, we consecutively operated on 219 patients. The average operating time was 275 minutes. The average time from the injection of the ICG solution to the start of the laparoscopic inspection was 25 minutes (12-55), while the F-ICG-guided-PLND and the ePLND for validation took an average of 142 min (97-189). Almost 52% of patients had pathologically extra-capsular disease, 24.2% had positive margins. 

F-ICG-guided-PLND was feasible in all patients. The media ICG-stained-LN per patient was 6. The median LN per patient, excised during the extended lymphadenectomy was 22. LNMs were found in 25.7% of patients.  Most of them had a single 30 metastasis (52%), but there were two patients with 12 or 23 metastasis. No adverse effects related to the ICG injection were documented. 

Importantly, 53 out of the 58 patients had some of their LNM in ICG-stained-LN, with only 5 false negatives documented. The sensitivity for ICG guided lymph node dissection for detecting metastatic patient was 91.38% and the negative predictive value (NPV) was 96.99%. Regarding the number of nodes in the entire sample, 4780 were removed, and 1535 were ICG-stained-LN. Pathological examination revealed 172 metastatic nodes, 109 (63%) of which were ICG-stained-LN. 

F-ICG-stained-LN, and therefore metastasis were located in most of them in the proximal internal iliac artery, followed by the external and common bifurcation regions. 2

Conclusion

ICG helps us improve pelvic lymphadenectomy in prostate cancer and is the appropriate technique for regional staging during radical prostatectomy, but may not have the same cytoreductive capacity as extended lymphadenectomy.
1. Van Hemelrijck M, Folkvaljon Y, Adolfsson J, Akre O, Holmberg L, Garmo H, et al. Causes of death in men with localised prostate cancer: a nationwide, population-based study. BJU Int 2015.
2. Ramirez-Backhaus M, Mira Moreno A, Gomez Ferrer A, Calatrava Fons A, Casanova J, Solsona Narbon E, et al. Indocyanine Green Guided Pelvic Lymph Node Dissection: An Efficient Technique to Classify the Lymph Node Status of Patients with Prostate Cancer Who Underwent Radical Prostatectomy. J Urol 2016;196:1429-35.
3. Rogasch JM, Cash H, Zschaeck S, Elezkurtaj S, Brenner W, Hamm B, et al. Ga-68-PSMA PET/CT in treatment-naive patients with prostate cancer: Which clinical parameters and risk stratification systems best predict PSMA-positive metastases? Prostate 2018.