Surgeons Perspective: LN as a Draining Pattern. Jose A. Karam, MD, FACS Associate Professor Department of Urology
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1 Surgeons Perspective: LN as a Draining Pattern Jose A. Karam, MD, FACS Associate Professor Department of Urology
2 Disclosures EMD Serono, Pfizer, Novartis: Advisory board/consultant
3 Disclosures I perform lymph node dissection in selected patients
4 Why Even Bother with Lymph Node Dissection?
5 A BIT OF HISTORY
6 Historical Studies on Lymph Nodes Nuck A Mascagni P Poirier P, Cuneo B Kubik S. 2006
7 LND BASED ON SENTINEL NODE MAPPING
8 Sentinel Lymph Nodes-Pilot Study N=8 99m Tc colloid Lymphoscintigraphy SPECT/CT Bex A. Eur J Nucl Med Mol Imaging. 2010
9 Bex A et al Sentinel Lymph Nodes 20 patients (16 ccrcc) 14 patients with at least 1 SNL (Total SNL=26) Sherif A et al 11 patients (all ccrcc) 10 patients with at least 1 SNL (Total SNL=32) Bex A. World J Urol Sherif A. BJU Int. 2012
10 Issues to Keep in Mind in Sentinel Node Studies Size of tumor Dose of radiotracer Location of tracer injection (periphery vs center) Tumors can undergo different levels of lymphangiogenesis causing significant variations in lymphatic remodeling Timing of lymphoscintigraphy Preoperative SPECT/CT type Intraoperative sampling (in situ vs ex situ) Padera TP. Science Karmali R. BJU Int. 2014
11 Summary of Renal Lymphatic Drainage Right Kidney Left Kidney Anterior Efferent Lymphatic Vessels A. Paracaval B. Precaval C. Interaortocaval a. Retrocaval D. Preaortic E. Para-aortic Posterior Efferent Lymphatic Vessels A. Paracaval a. Retrocaval C. Interaortocaval - Thoracic duct D. Para-aortic b. Retroaortic - Thoracic duct Karmali R. BJU Int. 2014
12 Silvester CF. Am J Anat Job TT. Am J Anat Engeset TA. J Anat Roddenberry H. Anat Rec Lympho-Venous Communications (Animals) Primate Rat Primate
13 Drainage into Thoracic Duct Drainage into thoracic duct without any retroperitoneal node metastasis 4 patients underwent lymphoscintigraphy and SPECT/CT Early lymphatic drainage into the thoracic duct 1 patient had no retroperitoneal metastasis Assouad J. Lymphology Assouad J. Eur J Cardiothorac Surg Brouwer OR. Lymphat Res Biol 2013
14 Other Techniques for Sentinel Nodes FDG PET High specificity (100%), low sensitivity (75%) for detecting lymph node metastasis Lymphotropic nanoparticle-enhanced MRI High specificity (100%) and sensitivity (95.5%) PET/MRI (preclinical animal models) using 89 Zrfurmoxytol Kang DE. J Urol Guimaraes AR. Urology Thorek DL. Nature Commun. 2014
15 Future of Sentinel Node Mapping? IndoCyanine Green (ICG) with Near-Infrared Imaging (NIR) Used/studied in: Uterine/cervical cancers Melanoma Breast cancer Lung cancer
16 Proposed Protocol-MD Anderson Patients at high-risk of lymph node metastasis Clinical stage T2 or higher, fat invasion, or renal vein/ivc invasion Methods: CT renal protocol will be performed on all patients preoperatively Sentinel lymph node mapping will be performed on all patients intraoperatively using ICG RPLND will be performed on all patients CT findings and sentinel lymph node mapping results will be correlated with postoperative pathology evaluation
17 LND BASED ON PREOPERATIVE FACTORS
18 Preoperative Prediction of pn+ (2007) 4,658 patients 12 institutions ( ) pt3-4 in ~30% pn+ in 207 (4.2%)-N nodes removed? M+? Hilar LND only Hutterer GC. Int J Cancer. 2007
19 Preoperative Prediction of pn+ (2007) AUC= 78.4% Hutterer GC. Int J Cancer. 2007
20 Preoperative Prediction of pn+ (2013) 1,983 patients, single-institution ( ) No LND (n= 1109, 55.9%) Limited LND (n= 394, 19.9%) Side-specific LND (n= 293, 14.8%) Extended LND (n= 187, 9.4%) Capitanio U. BJU Int. 2013
21 Preoperative Prediction of pn+ (2013) ct3-4 = 9.6% cn1 = 12.9% M1 = 12.1% pn+ or LN progression = 8.8% Capitanio U. BJU Int. 2013
22 Preoperative Prediction of pn+ (2013) Accuracy 86.9% Capitanio U. BJU Int. 2013
23 Preoperative Prediction of pn+ (2015) 1,270 patients with M0 RCC 564 had RPLND (cn+ in 28.7%) 131 patients (23%) had pn+ Babaian KN. J Urol. 2015
24 Preoperative Prediction of pn+ (2015) Variable OR (95% CI) P ECOG PS (1 or greater vs 0) 2.03 ( ) 0.02 cn stage (cn1 vs cn0) ( ) < Local symptoms (yes vs no) 3.29 ( ) LDH (increased vs normal) 2.56 ( ) Babaian KN. J Urol. 2015
25 Nomogram Predicting Probability Of LN Metastasis C-index 0.89 Babaian KN. J Urol. 2015
26 Radiographic Prediction of pn+ Mayo Clinic 220 patients RN+LND (2000 to 2010) Two variables associated with pn+ Maximum LN short axis diameter (OR 1.19) Radiographic perinephric/sinus fat invasion (OR 44.64) AUC 0.85 Gershman B. BJU Int. 2016
27 LND BASED ON INTRAOPERATIVE FACTORS
28 1652 patients ( ) ccrcc cn0m0 had radical nephrectomy 955 patients had concurrent LND pn1: 57 (3%) pn2: 11 (1%) Blute ML. J Urol. 2004
29 Intraoperative Predictors of pn+ Feature OR (95% CI) p Grade 3+4 (vs. 1+2) 5.25 ( ) <0.001 Sarcomatoid component 4.11 ( ) <0.001 Tumor 10 cm 2.17 ( ) pt3+pt4 (vs. pt1+pt2) 2.00 ( ) Histological tumor necrosis 1.86 ( ) Blute ML. J Urol. 2004
30 Number of Features Associated with pn+ Number of Features pn0 pn (99.6) 3 (0.4) (99.0) 3 (1.0) (95.7) 12 (4.4) (87.6) 26 (12.4) (86.8) 16 (13.2) 5 7 (46.7) 8 (53.3) Blute ML. J Urol. 2004
31 Validation Study 415 patients ccrcc ( ) had radical nephrectomy 169 patients had 2 high risk features on intraoperative pathology 64 (38%) had pn+ Crispen PL. Eur Urol. 2011
32 Keep in Mind 35% of the patients had M1 disease Median number of lymph nodes = 6 (IQR: 3 13) Crispen PL. Eur Urol. 2011
33 Number Of Risk Factors And Presence Of Positive Lymph Nodes Number Of Positive Risk Factors Percentage Of Total Patients Percentage Of Patients With Positive Lymph Nodes 2 21% (35/169) 20% (7/35) 3 42% (71/169) 37% (26/71) 4 31% (53/169) 49% (26/53) 5 6% (10/169) 50% (5/10) Crispen PL. Eur Urol. 2011
34 Location Of Positive Lymph Nodes Based On Side Of Primary Tumor Crispen PL. Eur Urol. 2011
35 OUTCOMES FOR CONCURRENT LND IN N+MO PATIENTS AT TIME OF NEPHRECTOMY
36 Survival after Concurrent LND for pn+m0 MD Anderson Cancer Center 2,521 patients M0 ( ) had RN 68 patients pn+ Delacroix SE. J Urol. 2011
37 Survival after Concurrent LND for pn+m0 5-year OS = 37% Median 32 months 5-year DSS = 39% Median 32 months Delacroix SE. J Urol. 2011
38 Survival after Concurrent LND for pn+m0 Surgery could help a group of patients with pn+ M0 Papillary histology Complete resection Low number of positive nodes Absence of sarcomatoid dedifferentiation ECOG PS 0 or 1 Delacroix SE. J Urol. 2011
39 Survival after Concurrent LND for pn+m0 Mayo Clinic 138 patients with isolated pn1m0 RCC Median time to metastases 4.2 months 5-year CSS 26% 5-year OS 25% Gershman B. Eur Urol. 2017
40 Survival after Concurrent LND for pn+m0 Poor prognostic indicators: Symptoms at presentation Clear cell and collecting duct/nos pt3b/c pt4 Coagulative tumor necrosis Gershman B. Eur Urol. 2017
41 OUTCOMES FOR SALVAGE LND IN N+ PATIENTS, AFTER NEPHRECTOMY
42 Salvage LND at Recurrence-1 MD Anderson Cancer Center Databases of patients who had partial or radical nephrectomy (>6,000 patients) 41 patients (<1%) with isolated LN recurrence after radical nephrectomy 5-yr CSS 50% Thomas AZ. J Urol. 2015
43 Salvage LND at Recurrence-2 Mayo, Moffitt, Roswell Park, McGill Databases of patients who had radical nephrectomy (>5,000 patients) 50 patients (<1%) with isolated LN recurrence after radical nephrectomy 5-yr PFS 35.4% Russell CM. J Urol. 2015
44 Potential Algorithm cn1 Yes LND (Concurrent) N status at time of RN in M0 cn0 No LND Later pn1 M0 (<1%) Yes LND (Salvage) M1 No LND
45 Take Home Messages Need to refine sentinel node mapping (Use ICG?) LN involvement is usually a harbinger of systemic disease In cn0m0, is there a difference in survival for immediate LND for pn+ versus salvage LND for pnx with later LN recurrence? LND is mostly diagnostic Might help put the rare patient with pt1-2pn1 on adjuvant trials LND is rarely therapeutic -in select cases (LN-mets-only phenotype?) Papillary, low volume nodal disease, good PS, no sarcomatoid
46 Questions?
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