MultiSPectral fLuorescence Imaging as a Tool to separate healthy and disease related lymphatic anatomies during lymph node dissections in prostate cancer.

We hypothesized that real-time multispectral fluorescence imaging of both the
lymphangiographic tracer fluorescein and the SN specific tracer
ICG-99mTc-nanocolloid is technically feasible and will allow us to
differentiate the lymphatic drainage profiles of healthy tissues, i.e. those of
the lower limbs (fluorescein) from those of the primary tumour
(ICG-99mTc-nanocolloid), respectively (Figure 1). The potential of this concept
was previously evaluated in male pigs (n = 5) (Meershoek et al. JNM 2018;
Meershoek et al. JRS 202021,22). Here, the lymph nodes that drained the lower
limbs were differentiated from the lymph nodes that drained the prostate.
Uniquely, no overlap could be observed between the lymphatic drainage pathways.
The chance of complications for ePLND vs limited PLND is much higher (OR =
2.118, 95% CI: 1.107*4.051, z = 2.27, P*= .023) (Zheng et al, prec. Med.
Sciences 2020)23, and is related to the number of lymph nodes resected. In
Rousseau et al. (prog urol. 2014) it is suggested that sparing the lateral side
of the iliac artery at the lateral dissection reduced risk of lymphatic
complications without decreasing metastasis detection rate24. Hence, we feel
that we are obliged to study whether in the future non-tumor-associated lymph
nodes i.e. of the lower limbs, in humans can remain in situ.

We aim to evaluate the technical feasibility of imaging two different lymphatic
drainage profiles, namely that of healthy tissue (i.e. the lower
limbs/abdominal wall) and that of the primary tumor (i.e. prostate). To realize
the differentiation, real-time multispectral fluorescence imaging of two
spectrally different tracers (the lymphangiographic tracer fluorescein
(injected in the lower limbs and abdominal wall) and SN specific tracer
ICG-nanocolloid (injected in the tumor)) will allow for multispectral (or
multicolor) fluorescence imaging.

An investigator initiated, prospective, non-randomized, feasibility study.

Group A: The injection of fluorescein in the lower limb(s) is the only
deviation from existing procedures (in prostate cancer the use of
ICG-99mTc-nanocolloid has already been evaluated in 452 patients at the NKI. A
previous study using intraprostatic administration of both fluorescein and
ICG-99mTc-nanocolloid in the same patient has shown that the use of fluorescein
does not expose the patients to any additional risk (vd Berg et al., Eur Urol
2017 (n=10))1. A negligible risk involved with participation are allergy
towards fluorescein or ICG. Fluorescein comes as a slightly basic compound.
This could cause a stinging feeling when injected, which is why this is done
when the patient is under general anaesthesia starting with 1:5 dilution with
saline 0.9%. Both compounds are clinically approved, have been extensively used
in humans and their allergy profile has been specified. Of important note, the
dissection templates of the ePLND procedure will not be changed for this study
and only additional SN*s identified via ICG-99mTc-nanocolloid will be resected
(as has been done previously in n=452). The urine and the skin at the
injection site may remain coloured for up to 2 days after injection. In Chang
et al., Asian. J. surg. 2019, no anaphylaxis and no cases of skin necrosis at
injection site were observed2.

Group B: The injection of ICG in the abdominal wall is the only deviation from
existing procedures.

There are no other burdens. The benefit of the study is that insight into the
lymphatic anatomy may in the future lead to less invasive procedures that spare
lymphatic structures that are not related to the primary tumor and as such
reduce the toxicity and complications of PLND. Key herein is that the
oncological outcome is preserved.