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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

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  1. Pattern and implication of lymphatic drainage in renal tumors Axel Bex, MD, PhD The Netherlands Cancer Institute FOIU Tel Aviv, July 4, 2018

  2. 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”] I have the following financial interests or Disclosure code relationships to disclose: Pfizer C, S Roche C Genentech C Ipsen C Novartis C BMS C 2

  3. Recommendations from EAU guidelines on RCC – updated 2014 • • For T1 RCCs, nephron-sparing surgery should be performed whenever possible. For T1 RCCs, nephron-sparing surgery should be performed whenever possible. Open partial nephrectomy currently remains the standard. Open partial nephrectomy currently remains the standard. A A • • Laparoscopic radical nephrectomy is recommended in T2 renal cell cancer when nephron- Laparoscopic radical nephrectomy is recommended in T2 renal cell cancer when nephron- sparing surgery is not suitable sparing surgery is not suitable B B • • Extended lymphadenectomy does not improve survival and can be restricted to staging purposes. Extended lymphadenectomy does not improve survival and can be restricted to staging purposes. A A • • Adrenalectomy is generally not recommended except when a normal adrenal gland cannot be excluded Adrenalectomy is generally not recommended except when a normal adrenal gland cannot be excluded by imaging and palpation. by imaging and palpation. B B • • Patients with small tumours and/or signi fi cant comorbidity who are un fi t for surgery should be considered Patients with small tumours and/or signi fi cant comorbidity who are un fi t for surgery should be considered for an ablative approach for an ablative approach (eg, cryotherapy and radiofrequency ablation). (eg, cryotherapy and radiofrequency ablation). A A EAU Guidelines on RCC – 2014 update, Ljungberg et al, Eur Urol 67:913-24, 2015

  4. 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

  5. Preoperative nomogram to predict nodal metastases • 1983 patients with cT any cN any cM any • Prevalence of nodal metastases 6.1 % • Accuracy 86.9 % Capitanio et al., BJU Int 112: E59-66, 2013

  6. Is there a template for lymph node dissection in RCC ? N=31 patients with N+ >1 cm Hadley et al, Urologic Oncology 2009

  7. 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 99m Tc-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

  8. Contralateral paraaortic SN location

  9. Supraclavicular lymph node metastases 4/22 patients with SPECT- SN identification (18.2 %) Brouwer et al., Lymph Res Biol 11:233-38, 2013

  10. 65% inside LND templates 35% outside from which 20% in thoracic area Kuusk et al., J Urol 2018

  11. Parker was the first to describe connections to the thoracic duct Parker 1935

  12. 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

  13. Direct drainage into the thoracic duct without intervening lymph nodes 5 of 13 right side, 3 of 13 left side Assouad et al., Lymphology 39:26-32, 2006

  14. 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

  15. Distribution of lymph node metastasis • Imaging study on 28 patients with cN1 identified from 101 with RCC Location Percentage (left/right combined Distant lymphadenopathy 29 % without hilar lymphadenopathy Interaortocaval 42 % retroaortocaval 46 % suprahilar 30 % Hadley et al. Urol Oncol 2009

  16. Paraaortic TD subclavian vein lung mediastinal nodes Brouwer et al, Assoud et al

  17. 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

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