Sentinel Lymph Node Biopsy Is Valuable For All Cancer. Surgery Grand Rounds Debate October 6, 2008 Joel Baumgartner

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1 Sentinel Lymph Node Biopsy Is Valuable For All Cancer Surgery Grand Rounds Debate October 6, 2008 Joel Baumgartner

2 History Lymphatics first described by Rasmus Bartholin in 1653 Rudolf Virchow postulated that lymph nodes filter particulates from lymph

3 History Led to Halstedian en bloc resections at end of 19 th Century based on locoregional spread of cancer Animal studies in 1950s showed filtration of injected carcinoma cells by lymph nodes

4 SLNB Rationale Less invasive technique to evaluate status of draining LN basin from primary tumor Assumes determination of LN status is beneficial For therapeutic advantage For prognostic advantage Alternative is doing routine LN dissection or selective LN dissection once clinically positive

5 History First documented use of SLN concept during total parotidectomy by Gould in 1951 Gould E, et al. Cancer 1960;13:77-78

6 History First description of lymphatic mapping for SNLB in penile cancer by Cabañas in 1977 Performed penile lymphangiography in 100 patients, identifying an anatomically predictable SLN Performed blind SLN biopsy and completion LN dissection in 46 patients 15 were +, 12 of these without additional + LNs 31 were Cabanas. -, all Cancer without 1977;39: additional + LNs (0% FN rate)

7 Cabañas Description of SLNB Cabanas. Cancer 1977;39:

8 History SLN location variable Development of intraoperative techniques to identify SLN Initially studied in feline model: injection of vital blue dye, dissection of lymphatic channels to SLNs Isosulfan blue proved to be most useful Wong JH, et al. Ann Surg 1991;214:637.

9 History Further developments Radio-isotope labeling with technetium-99mlabeled colloid first described in feline model by Alex in 1993 Finer SLN sectioning IHC Alex J, et al. Surg Oncol 1993;2:

10 Cochran AJ, et al. Nat Rev Immunol 2006;6:

11 SLNB In Melanoma LN status an important prognostic factor in melanoma Balch CM, et al. J Clin Oncol 2001;19:

12 SLNB in Melanoma First description of routine use of SLNB in any cancer by Morton in 1992 Intradermal injection of isosulfan blue around tumor, incision in regional lymphatic basin, removal of blue-stained nodes, then completion LN dissection Of 223 patients, 21% with + SLNs 5% rate of + non-sentinel LNs (FN) Morton DL, et al. Arch surg 1992;127:

13 SLNB in Melanoma Morton s FN rate has been confirmed by others 2% FN rate in 118 SLNBs by Thompson et al. 0% FN rate in 42 SLNBs by Reintgen et al. SLN status an independent predictor of survival in study of 612 patients by Gershenwald Thompson JF, et et al. Melanoma al. Res 1995;5: Reintgen D, et al. ann surg 1994;220: Gershenwald JE, et al. J Clin Oncol 1999;17:

14 SLNB in Melanoma SLNB and survival Multicenter Selective Lymphadenectomy Trial (MSLT) RCT of 1269 patients with intermediatethickness melanoma to WLE + SLNB +/- LND vs. WLE + observation for clinically + LNs +/- LND 16% + SLN rate 3% FN SLNB rate Morton DL, et al. NEJM 2006;355:

15 SLNB Group With Higher Survival 78% vs. 73% Morton DL, et al. NEJM 2006;355:

16 SLN + Group With Higher Survival Than Observation Group 72% 52% Morton DL, et al. NEJM 2006;355:

17 SLNB In Breast Cancer + LNs are an independent risk factor for breast cancer mortality Carter CL, et al. Cancer 1989;63:

18 SLNB In Breast Cancer SLNB with intra-operative lymphatic mapping for breast cancer first described by Giuliano in % FN rate using dye only Noted differences from melanoma SLNB More isosulfan blue required High background radiation from proximity of tumor to axilla Guiliano AE, et al. Ann Surg 1994;220:

19 SLNB In Breast Cancer High SLN detection rate, low FN rate Hsueh EC, et al. J Am Coll Surg 1999;189:

20 SLNB In Breast Cancer Less morbidity with SLNB vs. ALND ALMANAC RCT of 1031 patients to SLNB +/- ALND vs. routine ALND 98% SLN localization rate 5% vs. 13% lymphedema (p < 0.001) 11% vs. 31% sensory loss (p < 0.001) Reduced drain usage, LOS and time to return to normal activities in SLNB group Improved QOL in SLNB group Mansel RE, et al. J Natl Cancer Inst 2006;98:

21 SLNB In Breast Cancer No proven difference in survival in SLNB +/- ALND vs. routine ALND RCT of 697 patients 95% SLNB localization rate, 17% FN rate, 29% + SLN rate SLNB arm with 1/2 lymphedema and numbness of ALND arm (p = 0.01 and < , respectively) 90% 5yr DFS in ALND arm vs. 88% in SLNB arm (p = 0.77), likely underpowered Survival results of NSABP B-32 still pending (RCT of 5000 pts) Zavagno G, et al. Ann Surg 2008;247:

22 SLNB In Colorectal Cancer Stage III disease with 50% 5yr survival vs. 75% for stage II disease Recommended minimum 12 LNs in resection Theoretic advantage To limit nodal resection and associated morbidity of deep mesenteric division

23 SLNB In Colorectal Cancer Variable results have been published % localization rate Up to 15-30% FN rate Up to 25% upstaging Most studies with poor localization rates and high % FN include advanced tumors with grossly positive LNs Bilchik et al with 0% FN rate using cytokeratin IHC and PCR for stage I-II tumors Cahill RA. World J Gastroenterol 2007;13: Bilchik AJ, et al. J Clin Oncol 2001;19:

24 SLNB In Gyn Cancers No RCTs, mostly feasibility trials Cervical CA Tx typically involves RP lymphadenectomy, but only 10% have + LNs 80-86% detection rate, 0-5% FN rate Endometrial CA: 50-80% detection rate, 0-15% FN rate Vulvar CA: 85-99% detection rate, 0-15% FN rate Ayhan A, et al. World J Surg Oncol 2008;6:53-64.

25 SLNB in Other Cancers Lung Cancer Blue dye less helpful because of black anthracosis in thoracic LNs 80-85% detection rate Esophageal cancer % detection rate, 15-25% FN rate Pancreatic cancer Only 1 published study with 9 patients Liptay MJ. Ann Thorac Surg 2008;85: Schlag PM, et al. Eur J Cancer 2004;40:

26 SLNB In Gastric Cancer Gastric cancer LN dissection important, although degree of lymphadenectomy controversial (D1 vs. D2) Schlag PM, et al. Eur J Cancer 2004;40:

27 SLNB In Other Cancers Merkel cell carcinoma H & N SCC Thyroid cancer

28 Future Directions Is completion LND necessary after + SLNB? MSLT-II looking at SLN + patients, randomized to completing LND vs. observation Meta-analysis of ALND studies in breast CA showed 5.4% survival advantage with LN dissection Macrometastasis vs. micrometastasis Orr RK. Ann Surg Oncol 1999;6:

29 Summary SLNB is feasible 95% detection rate in breast cancer SLNB is accurate FN rates around 5% for many different cancers Higher FN rates mostly from small, feasibility studies SLNB is less morbid 1/2 the lymphedema and neuropathy rate as complete LN dissection in breast cacner

30 Dr. Jordan Rat lymph doctor Lymphatologist