Pattern and implication of lymphatic

drainage in renal tumors Axel Bex, MD, PhD

The Netherlands Cancer Institute

FOIU Tel Aviv,

July 4, 2018

Financial and Other Disclosures Off-label use of drugs, devices, or other agents: None or FILL IN HERE; including your

local regulatory agency, such as FDA, EMA, etc.

Data from IRB-approved human research is presented [or state: “is not”]

2

I have the following financial interests or

relationships to disclose: Disclosure code

Pfizer C, S

Roche C

Genentech C

Ipsen C

Novartis C

BMS C

Recommendations from EAU guidelines on

RCC – updated 2014

• For T1 RCCs, nephron-sparing surgery should be performed whenever possible.

Open partial nephrectomy currently remains the standard. A

• Laparoscopic radical nephrectomy is recommended in T2 renal cell cancer when nephron-

sparing surgery is not suitable B

• Extended lymphadenectomy does not improve survival and can be restricted to staging purposes. A

• Adrenalectomy is generally not recommended except when a normal adrenal gland cannot be excluded

by imaging and palpation. B

• Patients with small tumours and/or significant comorbidity who are unfit for surgery should be considered

for an ablative approach

(eg, cryotherapy and radiofrequency ablation). A

EAU Guidelines on RCC – 2014 update, Ljungberg et al, Eur Urol 67:913-24, 2015

• For T1 RCCs, nephron-sparing surgery should be performed whenever possible.

Open partial nephrectomy currently remains the standard. A

• Laparoscopic radical nephrectomy is recommended in T2 renal cell cancer when nephron-

sparing surgery is not suitable B

• Extended lymphadenectomy does not improve survival and can be restricted to staging purposes. A

• Adrenalectomy is generally not recommended except when a normal adrenal gland cannot be excluded

by imaging and palpation. B

• Patients with small tumours and/or significant comorbidity who are unfit for surgery should be considered

for an ablative approach

(eg, cryotherapy and radiofrequency ablation). A

But……..

• The patient who can potentially be

cured by LND has very early lymph

node metastasis and no systemic

disease

Canfield et al., J Urol 175:864-869, 2006

Capitanio et al., BJU Int 112: E59-66, 2013

• 1983 patients with cT any cNany cMany

• Prevalence of nodal metastases 6.1 %

• Accuracy 86.9 %

Preoperative nomogram to predict nodal metastases

Is there a template for lymph node

dissection in RCC ?

Hadley et al, Urologic Oncology 2009

N=31 patients with N+ >1 cm

MATERIALS & METHODS

• OBJECTIVES: To study the lymphatic drainage of renal tumours

• 40 patients

• Local cT1-3 (<10 cm) cN0cM0

• US guided p/c injection of 0.4 ml 99mTc-nanocolloid into the tumour

• Preoperative lymphoscintigraphy with SPECT/CT

• Surgical treatment with intraoperative SN identification and sampling using a gamma probe

and mobile gamma camera

• SN and non-SN dissection

Contralateral paraaortic SN location

Supraclavicular lymph node metastases

4/22 patients with SPECT-

SN identification (18.2 %)

Brouwer et al., Lymph Res Biol 11:233-38, 2013

65% inside

LND

templates

35%

outside

from which

20% in

thoracic

area

Kuusk et al., J Urol 2018

Parker was the first to describe connections

to the thoracic duct

Parker 1935

1969 - A lymphographic and

histopathological investigation in RCC

• N=22 patients undergoing nephrectomy

• 7 (32 %) metastasis in lumbar and

ipsilateral iliac nodes

• 1 supraclavicular node

• Poor correlation of lymphography with

nodal metastasis but contrast filling of

mediastinal nodes observed

Hulten et al., Scand J Urol Nephrol 3:129-33, 1969

5 of 13 right side, 3 of 13 left side

Assouad et al., Lymphology 39:26-32, 2006

Direct drainage into the thoracic duct without

intervening lymph nodes

Distribution of lymph node metastases –

an autopsy study

• n= 1001 patients with metastatic RCC

Location %

neck + clavicle 20.7 %

mediastinum 10.3 %

hilus of lungs 66.2 %

hilus of kidney 7 %

paraaortal 26.8 %

retroperitoneal 36 %

mesenterial 14.4 %

Saitoh et al. J Urol 1982

Distribution of lymph node metastasis

• Imaging study on 28 patients with cN1 identified from

101 with RCC

Location Percentage (left/right

combined

Distant lymphadenopathy

without hilar

lymphadenopathy

29 %

Interaortocaval 42 %

retroaortocaval 46 %

suprahilar 30 %

Hadley et al. Urol Oncol 2009

Paraaortic TD subclavian vein lung mediastinal nodes

Brouwer et al, Assoud et al

Implications

• The pattern of lymphatic spread in RCC

is very unpredictable

• The true rate of single early occult LN

metastasis is unknown but seems low

• The sentinel node concept should be

studied in clinically high-risk cN0

patients or used for translational

research purposes