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Is pelvic sentinel node biopsy necessary for lower extremity and trunk melanomas?
The American Journal of Surgery xxx (2017) 1e5
Contents lists available at ScienceDirect
The American Journal of Surgery journal homepage: www.americanjournalofsurgery.com
Is pelvic sentinel node biopsy necessary for lower extremity and trunk melanomas? Darryl Schuitevoerder, MBBS a, *, Stanley P.L. Leong, MD b, Jonathan S. Zager, MD c, Richard L. White, MD d, Eli Avisar, MD e, Heidi Kosiorek, MS f, Amylou Dueck, PhD f, Jeanine Fortino, HIMA g, Mohammed Kashani-Sabet, MD b, Kyle Hart, MS a, John T. Vetto, MD g a
Department of Surgery, Oregon Health & Science University, Portland, OR, USA Center for Melanoma Research and Treatment, Department of Surgery, California Pacific Medical Center, San Francisco, CA, USA c Departments of Cutaneous Oncology and Sarcoma, Moffitt Cancer Center, Tampa, FL, USA d Department of Surgery, Levine Cancer Institute, Carolinas Medical Center, Charlotte, NC, USA e Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA f Section of Biostatistics, Mayo Clinic Arizona, Phoenix, AZ, USA g Department of Surgery, Division of Surgical Oncology, Oregon Health & Science University, Portland, OR, USA b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 17 December 2016 Received in revised form 17 January 2017 Accepted 21 March 2017
Objective: There is currently no consensus regarding how to address pelvic sentinel lymph nodes (PSLNs) in melanoma. Thus, our objectives were to identify the incidence and clinical impact of PSLNs. Methods: Retrospective review of a prospectively collected multi-institutional melanoma database. Results: Of 2476 cases of lower extremity and trunk melanomas, 227 (9%) drained to PSLNs (181 to both PSLNs and superficial (inguinal or femoral) sentinel lymph nodes (SSLN) and 46 to PSLNs alone). Seventeen (7.5%) of 227 PSLN cases were positive for nodal metastasis, 8 of which drained to PSLNs only while 9 drained to both PSLNs and SSLNs. Complication rates between PSLN and SSLN biopsy were similar (15% vs. 14% respectively). In 181 cases with drainage to both SSLNs and PSLNs, PSLN biopsy upstaged one patient (0.6%), and completion dissection based on a positive PSLN did not upstage any. Conclusions: PSLN biopsy is safe, however in the setting of negative SSLNs there is minimal clinical impact. We therefore recommend PSLN biopsy when the SSLNs are positive or when the tumor drains to PSLNs alone. © 2017 Elsevier Inc. All rights reserved.
Keywords: Pelvic node Iliac/obturator node Sentinel lymph node biopsy Melanoma
1. Introduction Sentinel lymph node biopsy (SLNB) remains central to the accurate staging of cutaneous melanoma. The current National Comprehensive Cancer Network guidelines recommend sentinel node biopsy for all melanomas greater than 1 mm thick and consideration of sentinel lymph node biopsy for thin melanomas with high-risk features.1 The status of the sentinel lymph node (SLN), defined as the node that receives direct drainage from the primary tumor,2 is widely accepted as the single most important prognostic factor for patients with cutaneous melanoma.3 The
* Corresponding author. Oregon Health & Science University, Department of Surgery, 3181 S.W. Sam Jackson Park Rd., Mail code L223, Portland, OR 97239, USA. E-mail address: [email protected] (D. Schuitevoerder).
current standard for localization of the sentinel node is the “dual dye technique” using a combination of preoperative lymphoscintigraphy/intraoperative gamma probe and intraoperative peritumoral blue dye injection. In the case of lower extremity and truncal melanomas, drainage to pelvic sentinel lymph nodes (iliac/obturator) (PSLN) is not uncommon. The exact incidence is unclear, however it has been reported as being observed in 8e23% of cases.4,5 The traditional teaching is that the skin of the lower extremity drains to inguinofemoral nodes (superficial sentinel lymph nodes or SSLNs) first and then to the pelvic nodes, while truncal lesions theoretically could drain to the pelvic nodes first via inferior epigastric lymphatic channels. However, this notion has been challenged, with reports of lower extremity afferent lymphatics leading directly to pelvic nodes.6,7
http://dx.doi.org/10.1016/j.amjsurg.2017.03.028 0002-9610/© 2017 Elsevier Inc. All rights reserved.
Please cite this article in press as: Schuitevoerder D, et al., Is pelvic sentinel node biopsy necessary for lower extremity and trunk melanomas?, The American Journal of Surgery (2017), http://dx.doi.org/10.1016/j.amjsurg.2017.03.028
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D. Schuitevoerder et al. / The American Journal of Surgery xxx (2017) 1e5
Among clinicians there is no consensus regarding how to address pelvic sentinel nodes for cutaneous melanomas of the lower extremity and trunk. There is a reluctance to perform PSLN biopsy for melanoma given it's technically challenging nature, potential for complications, and uncertainty as to whether the results will alter management. The incidence of pelvic nodal metastases in the setting of macro or micoremetastasis to the inguinofemoral nodes has been thoroughly examined,8e11 however in clinically node negative patients with drainage to PSLNs on lymphoscintigraphy the data is limited. Thus the objectives of this study were to identify the incidence of PSLNs, define the correlation between SSLNs and PSLNs, and in doing so, determine the clinical impact of PSLNs based on upstaging of disease. 2. Methods We performed a retrospective review of a prospectively collected, IRB approved, multi-institutional melanoma database (Sentinel Lymph Node Working Group; SLNWG). All clinically node negative patients undergoing SLNB for primary cutaneous melanoma of the lower extremity or trunk from 1993 to 2016 were reviewed. Of the 12 SLNWG institutions, only 7 contributed data regarding pelvic sentinel lymph nodes. Thus, the numbers we present are from these 7 contributing institutions only. During this time period, 2,476 patients were treated for lower extremity or trunk primary melanoma. One thousand three hundred thirty trunk and 14 cases of lower extremity melanoma did not drain to either PSLNs or SSLNs. Accordingly, these patients were included in order to determine the incidence of PSLN drainage, however they were not useful in further analysis due to lack of SSLN or PSLN drainage. All sentinel nodes were identified using radiocolloid, blue dye, or a combination of both. The sentinel node was defined as that receiving direct drainage from the tumor and the 10% rule was used to ensure complete removal of sentinel nodes.2,12 R statistics package version 3.0.2 (R Foundation for Statistical Computing, Vienna, Austria) was used to perform all statistical analysis.13 Pearson's chi-square test was used to compare categorical variables while Student's t-test or Wilcoxon rank-sum test were used to compare continuous variables. Multivariable logistic regression analysis was performed to determine predictors of PSLN drainage. For cases with drainage to both SSLNs and PSLNs, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated to determine the ability of the SSLN status to predict the outcome of PSLN biopsy. The pathological examination of the sentinel nodes was performed at each center using some modification of the Augsburg Consensus,14 including serial sectioning, H&E examination, and immunohistochemistry staining. 3. Results From 1993 to 2016 there were 2476 cases of primary lower extremity and trunk cutaneous melanomas. One thousand eighty-six had drainage to superficial (inguinal or femoral) sentinel lymph nodes (SSLN) and 227 (9%) drained to PSLNs (181 to both PSLNs and SSLNs and 46 to PSLNs alone) (Fig. 1). On univariable analysis, older age (52.4 vs 55.9, p ¼ 0.005) and tumor subtype (p < 0.001) were found to be significantly associated with identification of PSLNs (Table 1). On multivariable logistic regression analysis, older age (OR 1.01 for each 1-year increase, p ¼ 0.011), nodular melanoma subtype (OR 2.76, p ¼ 0.004), and other melanoma subtype (OR 2.40 p ¼ 0.003) were found to be predictive of drainage to pelvic sentinel nodes. Interestingly, primary tumor location and Breslow thickness were not found to be
Fig. 1. Stylistic representation of nodal drainage.
predictive of pelvic drainage (Table 2). Of the 227 cases with PSLN biopsy, 17 (7.5%) were positive for nodal metastasis; 8 patients had drainage to PSLNs only. The remaining 9 cases with a positive PSLN biopsy also had a SSLN biopsy with 8 out of the 9 cases having positive SSLNs. Eight of the 17 positive PSLN cases had completion pelvic node dissection, 2 (25%) having disease in non-sentinel nodes, both of which also had positive non-sentinel inguinofemoral nodes. On analysis of patient and tumor features in these 227 cases with PSLN biopsy, male sex, tumor thickness, and melanoma subtype were significantly
Table 1 Tumor features and demographics of patients undergoing SLNB by pelvic SLN status. Characteristics
No pelvic SLN (N ¼ 905)
Age 52.4 ± 16.9 Gender Male 357 (39%) Female 548 (61%) Tumor location LE 744 (82%) Trunk 161 (18%) Breslow Thickness (mm) Average 1.6 (1.1e2.6) Ulceration Yes 525 (72%) No 205 (28%) Mitotic rate <1/mm2 81 (16%) 1/mm2 415 (84%) Regression Yes 67 (16%) No 360 (84%) LVI Yes 76 (16%) No 405 (84%) Tumor subtype SS 197 (28%) Nodular 71 (10%) AL 86 (12%) Other 343 (49%)
Pelvic SLN (N ¼ 227)
p-Value
55.9 ± 16.2
0.005a
91 (40%) 136 (60%)
0.920b
186 (82%) 41 (18%)
1b
1.6 (1e2.7)
0.591c
129 (68%) 62 (32%)
0.272b
25 (23%) 85 (77%)
0.145b
13 (12%) 93 (88%)
0.464b
12 (12%) 91 (88%)
0.359b
27 (14%) 22 (11%) 23 (12%) 121 (63%)
<0.001b
x ± x indicates mean ± standard deviation; x.x (x.x e x.x) indicates median and inter-quartile range. LE: lower extremity; LVI: lymphovascular invasion; SS: superficial spreading; AL: acral lentiginous. Unknown values not represented in table and excluded from statistical analysis. a Student's t-test (two-sided). b Pearson's chi-squared test. c Wilcoxon rank-sum test with continuity correction.
Please cite this article in press as: Schuitevoerder D, et al., Is pelvic sentinel node biopsy necessary for lower extremity and trunk melanomas?, The American Journal of Surgery (2017), http://dx.doi.org/10.1016/j.amjsurg.2017.03.028
D. Schuitevoerder et al. / The American Journal of Surgery xxx (2017) 1e5 Table 2 Multivariable logistic regression model of PSLN drainage. Characteristic Age at diagnosis 1-year increase Location Trunk LE Melanoma Subtype Nodular Acral lentiginous Superficial spreading Other histology Breslow Thickness 1 mm increase Ulceration Present Absent Mitotic rate <1/mm2 1/mm2 Regression Present Absent LVI Present Absent
OR (95% CI)
p-Value
1.01 (1.00e1.02)
0.011
1.09 (0.72e1.64) 1
0.700
2.76 (1.37e5.56) 1.63 (0.80e3.32) 1 2.40 (1.34e4.29)
0.004 0.175
1.06 (0.99e1.13)
0.099
1.12 (0.75e1.66) 1
0.581
1 0.62 (0.35e1.11)
0.003
0.108
0.59 (0.29e1.21) 1
0.151
0.81 (0.41e1.62) 1
0.549
OR indicates odds ratio; CI indicates confidence interval. LE: lower extremity; LVI: lymphovascular invasion.
associated with positive PSLNs (Table 3). Of the 181 cases with drainage to both SSLNs and PSLNs the sensitivity and specificity of the SSLN status for determining PSLN biopsy outcome was 88.9% and 87.8% respectively. The NPV was 99.3% (CI 0.958e0.999) and the PPV was 27.6% (CI 0.134e0.475). In
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these 181 cases with drainage to both SSLNs and PSLNs, PSLN biopsy upstaged one patient (0.6%), and completion dissection based on a positive PSLN did not upstage any. Of the 46 cases of isolated PSLN without SSLN, 39 were from patients with LE primaries and 7 were from patients with truncal melanomas. In 3 cases popliteal SLNs were biopsied, in 2 cases axillary SLNs, and in 1 case an in-transit lymph node was biopsied. Regardless of the drainage pattern the complication rates between cases with PSLN and SSLN biopsy were similar (15 vs. 14% respectively, p ¼ 0.82). 4. Discussion Pending the results of the MSLT-II trial the current standard of care remains performance of a completion lymph node dissection for positive sentinel nodes. However, despite numerous prior studies, the management of pelvic lymph nodes remains unclear. Several studies show a high rate of positive pelvic lymph nodes after dissection of this nodal basin for either a positive SSLN or palpable disease in the inguinofemoral nodes (12e25% and 28e55% respectively).8e10,15e19 In our study the positive predictive value of the SSLN was 27.6%, meaning that if we had performed completion pelvic node dissection for the positive SSLNs in this study, 27.6% of cases would harbor positive nodes. These high rates of pelvic node metastases have led some to advocate for routine ilioinguinal lymphadenectomy for positive inguinofemoral nodes. However, it is uncertain whether such an approach confers benefit to the patient. A recent, albeit small, study by Egger et al. failed to show any advantage in terms of rates of lymph node recurrence, overall, or disease free survival when comparing patients who had inguinal and pelvic node dissection to those with inguinal dissection alone.8 Given these findings, it appears that if pelvic lymph node
Table 3 Tumor features and demographics of patients by PSLN biopsy status. Characteristics
Negative PSLN (N ¼ 210)
Positive PSLN (N ¼ 17)
p-Value
Age Gender Male Female Tumor location LE Trunk Breslow Thickness (mm) Average Ulceration Yes No Mitotic rate <1/mm2 1/mm2 Regression Yes No LVI Yes No Tumor subtype SS Nodular AL Other
55.8 ± 16.3
56.1 ± 15.9
0.943a
78 (37%) 132 (63%)
13 (76%) 4 (24%)
0.003b
173 (82%) 37 (18%)
13 (76%) 4 (24%)
0.518c
1.6 (1.1e2.6)
2.6 (1.9e6)
0.002d
55 (31%) 120 (69%)
7 (44%) 9 (56%)
0.466b
24 (24%) 77 (76%)
1 (11%) 8 (89%)
0.681c
13 (13%) 87 (87%)
0 (0%) 6 (100%)
1.000c
10 (10%) 87 (90%)
2 (33%) 4 (67%)
0.144c
25 (14%) 18 (10%) 20 (11%) 117 (65%)
2 4 3 4
0.021c
(15%) (31%) (23%) (31%)
x ± x indicates mean ± standard deviation; x.x (x.x e x.x) indicates median and inter-quartile range. PSLN: pelvic sentinel lymph node; LE: lower extremity; LVI: lymphovascular invasion; SS: superficial spreading; AL: acral lentiginous. Unknown values not represented in table and excluded from statistical analysis. a Student's t-test (two-sided). b Pearson's chi-squared test. c Fisher's exact test. d Wilcoxon rank-sum test with continuity correction.
Please cite this article in press as: Schuitevoerder D, et al., Is pelvic sentinel node biopsy necessary for lower extremity and trunk melanomas?, The American Journal of Surgery (2017), http://dx.doi.org/10.1016/j.amjsurg.2017.03.028
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D. Schuitevoerder et al. / The American Journal of Surgery xxx (2017) 1e5
dissection is performed in addition to inguinal node dissection for positive SSLN, we would be over-treating >70% of pelvic nodes. Thus, in the face of both inguinofemoral and pelvic sentinel nodes one might consider frozen section of the inguinofemoral sentinel node; if that node is negative there is no need for further PSLN biopsy (based on our finding of a NPV of 99%), however, if that node is positive one could consider performing PSLN biopsy to determine whether completion lymph node dissection of that basin is necessary. A similar approach has been to use the status of Cloquet's node during inguinofemoral dissection to determine the status of the pelvic nodes. However, variability in drainage patterns and low rates of disease involvement of this node has led some to question the reliability of this approach.20,21 In our study we found male sex, tumor thickness, and melanoma subtype to be predictive of positive PSLNs. However, given the small number of cases with a positive PSLN, 17, it is difficult to draw definitive conclusions from this data, and these findings should not influence the decision to perform PSLN biopsy. In the setting of both SSLN and PSLN biopsy, a negative SSLN was found to be an accurate and robust predictor of the absence of disease in the PSLN (NPV 99%). Out of the 152 such cases, 1 (0.7%) had a positive PSLN, the remainder were negative. This finding is in keeping with other studies that showed a 1e2.5% rate of pelvic lymph node recurrence after negative SSLN biopsy.15,22 Similarly, in a recent publication by Miranda et al., of 86 cases with drainage to both SSLNs and PSLNs, 74 had negative a SSLN biopsy. In all of these cases the PSLN was also negative.23 In 2476 cases of primary lower extremity and trunk cutaneous melanomas there were 227 cases of PSLNs identified (9%). This is similar to the 8% incidence found by van der Ploeg et al.,4 but considerably lower than the 23% described by Karakousis et al.5 The discrepancy here may be explained by the fact that in the study by Karakousis et al. the majority of cases had weaker tracer uptake in pelvic nodes and thus those nodes were often considered secondechelon, while ours represented the true sentinel node. Of the 227 cases of drainage to PSLNs, 46 (20%) drained exclusively to this basin without sentinel nodes identified in the inguinofemoral region. Of these, 39 were from LE primaries and 7 were from primary tumors of the trunk. This finding goes against the traditional dogma that pelvic nodes are considered second order, but is supported by other studies demonstrating similar lymphatic drainage patterns.6,7 Nevertheless out of these 46 cases of isolated pelvic sentinel node drainage, 8 (17%) were positive for metastatic disease, highlighting the need to perform SLNB in this situation. Furthermore we found PSLN biopsy to be safe with an equivalent complication rate to SSLN biopsy (15 vs 14% respectively). This finding is supported by a recent study by Chang et al. looking at postoperative complication rates for inguinofemoral node dissection. In their study the addition of pelvic node dissection did not significantly increase the risk of wound complications.24 5. Conclusions In conclusion, we found PSLN biopsy to be safe, with an equivalent complication rate to SSLN biopsy. The fact that 20% of cases with PSLNs identified did not have drainage to SSLN challenges the traditional teaching that lower extremity melanoma always drains in a stepwise fashion and warrants consideration when dealing with this disease process. In this situation, isolated pelvic nodes should be biopsied in order to provide accurate staging. However, in the face of drainage to both SSLNs and PSLNs, the finding of negative SSLNs almost always predicted negative PSLNs. Thus performing routine PSLN biopsy appears to hold minimal clinical impact. Given the poor PPV of SSLNs, in the setting of positive SSLNs, PSLN biopsy could be used to determine which patients
would benefit from pelvic node dissection. Therefore, we would recommend PSLN biopsy when the SSLNs are positive or when the tumor drains only to pelvic nodes. Conflict of interest None. References 1. Network NCC. Melanoma. https://www.nccn.org/professionals/physician_gls/ pdf/melanoma.pdf. Accessed Oct. 29th, 2016. 2. Nieweg OE, Tanis PJ, Kroon BB. The definition of a sentinel node. Ann Surg Oncol. 2001;8(6):538e541. 3. Balch CM, Gershenwald JE, Soong SJ, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol Of J Am Soc Clin Oncol. 2009;27(36): 6199e6206. 4. van der Ploeg IM, Kroon BB, Valdes Olmos RA, Nieweg OE. Evaluation of lymphatic drainage patterns to the groin and implications for the extent of groin dissection in melanoma patients. Ann Surg Oncol. 2009;16(11): 2994e2999. 5. Karakousis GC, Pandit-Taskar N, Hsu M, et al. Prognostic significance of drainage to pelvic nodes at sentinel lymph node mapping in patients with extremity melanoma. Melanoma Res. 2013;23(1):40e46. 6. Everett M, Gutman H. Lymphatic drainage of calf melanoma skipping the superficial groin. Lymphat Res Biol. 2007;5(4):265e268. 7. Miura H, Ono S, Nagahata M, et al. Lymphoscintigraphy for sentinel lymph node mapping in Japanese patients with malignant skin neoplasms of the lower extremities: comparison with previously investigated Japanese lymphatic anatomy. Ann Nucl Med. 2010;24(8):601e608. 8. Egger ME, Brown RE, Roach BA, et al. Addition of an iliac/obturator lymph node dissection does not improve nodal recurrence or survival in melanoma. J Am Coll Surg. 2014;219(1):101e108. 9. Glover AR, Allan CP, Wilkinson MJ, Strauss DC, Thomas JM, Hayes AJ. Outcomes of routine ilioinguinal lymph node dissection for palpable inguinal melanoma nodal metastasis. Br J Surg. 2014;101(7):811e819. 10. Niebling MG, Wevers KP, Suurmeijer AJ, van Ginkel RJ, Hoekstra HJ. Deep lymph node metastases in the groin significantly affects prognosis, particularly in sentinel node-positive melanoma patients. Ann Surg Oncol. 2015;22(1): 279e286. 11. Glumac N, Hocevar M, Zadnik V, Snoj M. Inguinal or inguino-iliac/obturator lymph node dissection after positive inguinal sentinel lymph node in patients with cutaneous melanoma. Radiol Oncol. 2012;46(3):258e264. 12. Emery RE, Stevens JS, Nance RW, Corless CL, Vetto JT. Sentinel node staging of primary melanoma by the “10% rule”: pathology and clinical outcomes. Am J Surg. 2007;193(5):618e622. discussion 622. 13. R Core Team. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing; 2013. ISBN 3-900051-07-0. Available at: http://www.R-project.org. 14. Cochran AJ, Balda BR, Starz H, et al. The Augsburg Consensus. Techniques of lymphatic mapping, sentinel lymphadenectomy, and completion lymphadenectomy in cutaneous malignancies. Cancer. 2000;89(2):236e241. 15. Soteldo J, Ratto EL, Gandini S, et al. Pelvic sentinel lymph node biopsy in melanoma patients: is it worthwhile? Melanoma Res. 2010;20(2):133e137. 16. Mozzillo N, Pasquali S, Santinami M, et al. Factors predictive of pelvic lymph node involvement and outcomes in melanoma patients with metastatic sentinel lymph node of the groin: a multicentre study. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol. 2015;41(7):823e829. 17. Allan CP, Hayes AJ, Thomas JM. Ilioinguinal lymph node dissection for palpable metastatic melanoma to the groin. ANZ J Surg. 2008;78(11):982e986. 18. Zdzienicki M, Rutkowski P, Nowecki ZI, et al. The analysis of the outcomes and factors related to iliac-obturator involvement in cutaneous melanoma patients after lymph node dissection due to positive sentinel lymph node biopsy or clinically detected inguinal metastases. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol. 2013;39(3):304e310. 19. Chu CK, Delman KA, Carlson GW, Hestley AC, Murray DR. Inguinopelvic lymphadenectomy following positive inguinal sentinel lymph node biopsy in melanoma: true frequency of synchronous pelvic metastases. Ann Surg Oncol. 2011;18(12):3309e3315. 20. Teramoto Y, Nakamura Y, Sato S, Yamazaki N, Yamamoto A. Low probability of lymphatic drainage to Cloquet's node is of limited value as indicator for pelvic lymph node dissection in patients with lower limb melanoma. Lymphat Res Biol. 2016;14(2):109e114. 21. Chu CK, Zager JS, Marzban SS, et al. Routine biopsy of Cloquet's node is of limited value in sentinel node positive melanoma patients. J Surg Oncol. 2010;102(4):315e320. 22. Essner R, Scheri R, Kavanagh M, Torisu-Itakura H, Wanek LA, Morton DL. Surgical management of the groin lymph nodes in melanoma in the era of sentinel lymph node dissection. Arch Surg. 2006;141(9) (Chicago, Ill: 1960) 877-882; discussion 882e874. 23. Miranda SG, Parrett BM, Li RR, et al. Selective sentinel lymph node dissection in lower extremity melanoma. Plastic Reconstr Surg. 2016;137(3):1031e1038.
Please cite this article in press as: Schuitevoerder D, et al., Is pelvic sentinel node biopsy necessary for lower extremity and trunk melanomas?, The American Journal of Surgery (2017), http://dx.doi.org/10.1016/j.amjsurg.2017.03.028
D. Schuitevoerder et al. / The American Journal of Surgery xxx (2017) 1e5 24. Chang SB, Askew RL, Xing Y, et al. Prospective assessment of postoperative complications and associated costs following inguinal lymph node dissection (ILND) in melanoma patients. Ann Surg Oncol. 2010;17(10):2764e2772.
Discussion: Vance Sohn, MD; Gig Harbor, WA I would like to thank Drs Schuitevoerder and Vetto on their work entitled “Is Pelvic Sentinel Node Biopsy Necessary for Lower Extremity and Trunk Melanomas?” In their retrospective analysis of a multi-institutional melanoma database, the authors challenge the notion that lymphatic spread for melanoma occurs in an orderly, step wise fashion, the so called spectrum theory. The authors sought to identify the incidence of pelvic sentinel lymph nodes, define the correlation between superficial and pelvic sentinel nodes, and to determine the clinical impact of pelvic sentinel lymph nodes. Over a 23 year experience, 227 of the 2476 clinically node negative lower extremity and truncal melanomas that underwent pelvic sentinel node sampling comprised the study cohort. Of the 227, 181 had both pelvic and superficial nodal drainage and 46 had only pelvic drainage. These 46 patients are the most interesting to me, with 39 patients who had lower extremity melanoma with only deep groin nodes. A notable conclusion of their findings was that 20% of cases with pelvic sentinel lymph nodes did not have drainage to the superficial nodal basin and therefore. Furthermore, the authors suggest that if there are both superficial and pelvic sentinel nodes, but the superficial node is negative, then the need
5
for a deep node biopsy is obviated. I would like to congratulation the authors on addressing an interesting, albeit unusual, clinical issue. My questions include: 1. Based on my own personal experience, I imagine that SLN sampling, particularly for lower extremity melanomas, is grossly underestimated and underperformed by most oncologic surgeons. Certainly for truncal melanomas that have variable drainage patterns, pre-operative mapping is essential; however, for most lower extremity melanomas, routine mapping is not performed. In light of the recommendation that routine Stage III cancers do not undergo routine pre-operative imaging unless indicated, how are pelvic nodes identified pre-operatively1? At your institution, who gets pre-operative lymphoscintography? 2. The study period encompasses patients who were enrolled starting 1993 and yet, Dr Morton first described the technique for melanoma first at the SSO in 1990.2 During your analysis, did the era of the diagnosis, especially when sentinel node sampling was in it's infancy, affect any of your findings? 3. I am curious to hear the authors perspectives on how these findings may alter the NCCN recommendations regarding a deep pelvic lymphadenectomy. Again, congratulations on an interesting paper.
1 NCCN Melanoma, https://www.nccn.org/professionals/physician_gls/pdf/ melanoma.pdf, Version1.2017, accessed 1 November 2016. 2 Morton D, Cagle L, Wong J, et al. Intraoperative lymphatic mapping and selective lymphadenectomy: technical details of a new procedure for clinical stage I melanoma. Presented at the Annual Meeting of the Society of Surgical Oncology; Washington, DC. 1990.
Please cite this article in press as: Schuitevoerder D, et al., Is pelvic sentinel node biopsy necessary for lower extremity and trunk melanomas?, The American Journal of Surgery (2017), http://dx.doi.org/10.1016/j.amjsurg.2017.03.028
Contents lists available at ScienceDirect
The American Journal of Surgery journal homepage: www.americanjournalofsurgery.com
Is pelvic sentinel node biopsy necessary for lower extremity and trunk melanomas? Darryl Schuitevoerder, MBBS a, *, Stanley P.L. Leong, MD b, Jonathan S. Zager, MD c, Richard L. White, MD d, Eli Avisar, MD e, Heidi Kosiorek, MS f, Amylou Dueck, PhD f, Jeanine Fortino, HIMA g, Mohammed Kashani-Sabet, MD b, Kyle Hart, MS a, John T. Vetto, MD g a
Department of Surgery, Oregon Health & Science University, Portland, OR, USA Center for Melanoma Research and Treatment, Department of Surgery, California Pacific Medical Center, San Francisco, CA, USA c Departments of Cutaneous Oncology and Sarcoma, Moffitt Cancer Center, Tampa, FL, USA d Department of Surgery, Levine Cancer Institute, Carolinas Medical Center, Charlotte, NC, USA e Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA f Section of Biostatistics, Mayo Clinic Arizona, Phoenix, AZ, USA g Department of Surgery, Division of Surgical Oncology, Oregon Health & Science University, Portland, OR, USA b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 17 December 2016 Received in revised form 17 January 2017 Accepted 21 March 2017
Objective: There is currently no consensus regarding how to address pelvic sentinel lymph nodes (PSLNs) in melanoma. Thus, our objectives were to identify the incidence and clinical impact of PSLNs. Methods: Retrospective review of a prospectively collected multi-institutional melanoma database. Results: Of 2476 cases of lower extremity and trunk melanomas, 227 (9%) drained to PSLNs (181 to both PSLNs and superficial (inguinal or femoral) sentinel lymph nodes (SSLN) and 46 to PSLNs alone). Seventeen (7.5%) of 227 PSLN cases were positive for nodal metastasis, 8 of which drained to PSLNs only while 9 drained to both PSLNs and SSLNs. Complication rates between PSLN and SSLN biopsy were similar (15% vs. 14% respectively). In 181 cases with drainage to both SSLNs and PSLNs, PSLN biopsy upstaged one patient (0.6%), and completion dissection based on a positive PSLN did not upstage any. Conclusions: PSLN biopsy is safe, however in the setting of negative SSLNs there is minimal clinical impact. We therefore recommend PSLN biopsy when the SSLNs are positive or when the tumor drains to PSLNs alone. © 2017 Elsevier Inc. All rights reserved.
Keywords: Pelvic node Iliac/obturator node Sentinel lymph node biopsy Melanoma
1. Introduction Sentinel lymph node biopsy (SLNB) remains central to the accurate staging of cutaneous melanoma. The current National Comprehensive Cancer Network guidelines recommend sentinel node biopsy for all melanomas greater than 1 mm thick and consideration of sentinel lymph node biopsy for thin melanomas with high-risk features.1 The status of the sentinel lymph node (SLN), defined as the node that receives direct drainage from the primary tumor,2 is widely accepted as the single most important prognostic factor for patients with cutaneous melanoma.3 The
* Corresponding author. Oregon Health & Science University, Department of Surgery, 3181 S.W. Sam Jackson Park Rd., Mail code L223, Portland, OR 97239, USA. E-mail address: [email protected] (D. Schuitevoerder).
current standard for localization of the sentinel node is the “dual dye technique” using a combination of preoperative lymphoscintigraphy/intraoperative gamma probe and intraoperative peritumoral blue dye injection. In the case of lower extremity and truncal melanomas, drainage to pelvic sentinel lymph nodes (iliac/obturator) (PSLN) is not uncommon. The exact incidence is unclear, however it has been reported as being observed in 8e23% of cases.4,5 The traditional teaching is that the skin of the lower extremity drains to inguinofemoral nodes (superficial sentinel lymph nodes or SSLNs) first and then to the pelvic nodes, while truncal lesions theoretically could drain to the pelvic nodes first via inferior epigastric lymphatic channels. However, this notion has been challenged, with reports of lower extremity afferent lymphatics leading directly to pelvic nodes.6,7
http://dx.doi.org/10.1016/j.amjsurg.2017.03.028 0002-9610/© 2017 Elsevier Inc. All rights reserved.
Please cite this article in press as: Schuitevoerder D, et al., Is pelvic sentinel node biopsy necessary for lower extremity and trunk melanomas?, The American Journal of Surgery (2017), http://dx.doi.org/10.1016/j.amjsurg.2017.03.028
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D. Schuitevoerder et al. / The American Journal of Surgery xxx (2017) 1e5
Among clinicians there is no consensus regarding how to address pelvic sentinel nodes for cutaneous melanomas of the lower extremity and trunk. There is a reluctance to perform PSLN biopsy for melanoma given it's technically challenging nature, potential for complications, and uncertainty as to whether the results will alter management. The incidence of pelvic nodal metastases in the setting of macro or micoremetastasis to the inguinofemoral nodes has been thoroughly examined,8e11 however in clinically node negative patients with drainage to PSLNs on lymphoscintigraphy the data is limited. Thus the objectives of this study were to identify the incidence of PSLNs, define the correlation between SSLNs and PSLNs, and in doing so, determine the clinical impact of PSLNs based on upstaging of disease. 2. Methods We performed a retrospective review of a prospectively collected, IRB approved, multi-institutional melanoma database (Sentinel Lymph Node Working Group; SLNWG). All clinically node negative patients undergoing SLNB for primary cutaneous melanoma of the lower extremity or trunk from 1993 to 2016 were reviewed. Of the 12 SLNWG institutions, only 7 contributed data regarding pelvic sentinel lymph nodes. Thus, the numbers we present are from these 7 contributing institutions only. During this time period, 2,476 patients were treated for lower extremity or trunk primary melanoma. One thousand three hundred thirty trunk and 14 cases of lower extremity melanoma did not drain to either PSLNs or SSLNs. Accordingly, these patients were included in order to determine the incidence of PSLN drainage, however they were not useful in further analysis due to lack of SSLN or PSLN drainage. All sentinel nodes were identified using radiocolloid, blue dye, or a combination of both. The sentinel node was defined as that receiving direct drainage from the tumor and the 10% rule was used to ensure complete removal of sentinel nodes.2,12 R statistics package version 3.0.2 (R Foundation for Statistical Computing, Vienna, Austria) was used to perform all statistical analysis.13 Pearson's chi-square test was used to compare categorical variables while Student's t-test or Wilcoxon rank-sum test were used to compare continuous variables. Multivariable logistic regression analysis was performed to determine predictors of PSLN drainage. For cases with drainage to both SSLNs and PSLNs, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated to determine the ability of the SSLN status to predict the outcome of PSLN biopsy. The pathological examination of the sentinel nodes was performed at each center using some modification of the Augsburg Consensus,14 including serial sectioning, H&E examination, and immunohistochemistry staining. 3. Results From 1993 to 2016 there were 2476 cases of primary lower extremity and trunk cutaneous melanomas. One thousand eighty-six had drainage to superficial (inguinal or femoral) sentinel lymph nodes (SSLN) and 227 (9%) drained to PSLNs (181 to both PSLNs and SSLNs and 46 to PSLNs alone) (Fig. 1). On univariable analysis, older age (52.4 vs 55.9, p ¼ 0.005) and tumor subtype (p < 0.001) were found to be significantly associated with identification of PSLNs (Table 1). On multivariable logistic regression analysis, older age (OR 1.01 for each 1-year increase, p ¼ 0.011), nodular melanoma subtype (OR 2.76, p ¼ 0.004), and other melanoma subtype (OR 2.40 p ¼ 0.003) were found to be predictive of drainage to pelvic sentinel nodes. Interestingly, primary tumor location and Breslow thickness were not found to be
Fig. 1. Stylistic representation of nodal drainage.
predictive of pelvic drainage (Table 2). Of the 227 cases with PSLN biopsy, 17 (7.5%) were positive for nodal metastasis; 8 patients had drainage to PSLNs only. The remaining 9 cases with a positive PSLN biopsy also had a SSLN biopsy with 8 out of the 9 cases having positive SSLNs. Eight of the 17 positive PSLN cases had completion pelvic node dissection, 2 (25%) having disease in non-sentinel nodes, both of which also had positive non-sentinel inguinofemoral nodes. On analysis of patient and tumor features in these 227 cases with PSLN biopsy, male sex, tumor thickness, and melanoma subtype were significantly
Table 1 Tumor features and demographics of patients undergoing SLNB by pelvic SLN status. Characteristics
No pelvic SLN (N ¼ 905)
Age 52.4 ± 16.9 Gender Male 357 (39%) Female 548 (61%) Tumor location LE 744 (82%) Trunk 161 (18%) Breslow Thickness (mm) Average 1.6 (1.1e2.6) Ulceration Yes 525 (72%) No 205 (28%) Mitotic rate <1/mm2 81 (16%) 1/mm2 415 (84%) Regression Yes 67 (16%) No 360 (84%) LVI Yes 76 (16%) No 405 (84%) Tumor subtype SS 197 (28%) Nodular 71 (10%) AL 86 (12%) Other 343 (49%)
Pelvic SLN (N ¼ 227)
p-Value
55.9 ± 16.2
0.005a
91 (40%) 136 (60%)
0.920b
186 (82%) 41 (18%)
1b
1.6 (1e2.7)
0.591c
129 (68%) 62 (32%)
0.272b
25 (23%) 85 (77%)
0.145b
13 (12%) 93 (88%)
0.464b
12 (12%) 91 (88%)
0.359b
27 (14%) 22 (11%) 23 (12%) 121 (63%)
<0.001b
x ± x indicates mean ± standard deviation; x.x (x.x e x.x) indicates median and inter-quartile range. LE: lower extremity; LVI: lymphovascular invasion; SS: superficial spreading; AL: acral lentiginous. Unknown values not represented in table and excluded from statistical analysis. a Student's t-test (two-sided). b Pearson's chi-squared test. c Wilcoxon rank-sum test with continuity correction.
Please cite this article in press as: Schuitevoerder D, et al., Is pelvic sentinel node biopsy necessary for lower extremity and trunk melanomas?, The American Journal of Surgery (2017), http://dx.doi.org/10.1016/j.amjsurg.2017.03.028
D. Schuitevoerder et al. / The American Journal of Surgery xxx (2017) 1e5 Table 2 Multivariable logistic regression model of PSLN drainage. Characteristic Age at diagnosis 1-year increase Location Trunk LE Melanoma Subtype Nodular Acral lentiginous Superficial spreading Other histology Breslow Thickness 1 mm increase Ulceration Present Absent Mitotic rate <1/mm2 1/mm2 Regression Present Absent LVI Present Absent
OR (95% CI)
p-Value
1.01 (1.00e1.02)
0.011
1.09 (0.72e1.64) 1
0.700
2.76 (1.37e5.56) 1.63 (0.80e3.32) 1 2.40 (1.34e4.29)
0.004 0.175
1.06 (0.99e1.13)
0.099
1.12 (0.75e1.66) 1
0.581
1 0.62 (0.35e1.11)
0.003
0.108
0.59 (0.29e1.21) 1
0.151
0.81 (0.41e1.62) 1
0.549
OR indicates odds ratio; CI indicates confidence interval. LE: lower extremity; LVI: lymphovascular invasion.
associated with positive PSLNs (Table 3). Of the 181 cases with drainage to both SSLNs and PSLNs the sensitivity and specificity of the SSLN status for determining PSLN biopsy outcome was 88.9% and 87.8% respectively. The NPV was 99.3% (CI 0.958e0.999) and the PPV was 27.6% (CI 0.134e0.475). In
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these 181 cases with drainage to both SSLNs and PSLNs, PSLN biopsy upstaged one patient (0.6%), and completion dissection based on a positive PSLN did not upstage any. Of the 46 cases of isolated PSLN without SSLN, 39 were from patients with LE primaries and 7 were from patients with truncal melanomas. In 3 cases popliteal SLNs were biopsied, in 2 cases axillary SLNs, and in 1 case an in-transit lymph node was biopsied. Regardless of the drainage pattern the complication rates between cases with PSLN and SSLN biopsy were similar (15 vs. 14% respectively, p ¼ 0.82). 4. Discussion Pending the results of the MSLT-II trial the current standard of care remains performance of a completion lymph node dissection for positive sentinel nodes. However, despite numerous prior studies, the management of pelvic lymph nodes remains unclear. Several studies show a high rate of positive pelvic lymph nodes after dissection of this nodal basin for either a positive SSLN or palpable disease in the inguinofemoral nodes (12e25% and 28e55% respectively).8e10,15e19 In our study the positive predictive value of the SSLN was 27.6%, meaning that if we had performed completion pelvic node dissection for the positive SSLNs in this study, 27.6% of cases would harbor positive nodes. These high rates of pelvic node metastases have led some to advocate for routine ilioinguinal lymphadenectomy for positive inguinofemoral nodes. However, it is uncertain whether such an approach confers benefit to the patient. A recent, albeit small, study by Egger et al. failed to show any advantage in terms of rates of lymph node recurrence, overall, or disease free survival when comparing patients who had inguinal and pelvic node dissection to those with inguinal dissection alone.8 Given these findings, it appears that if pelvic lymph node
Table 3 Tumor features and demographics of patients by PSLN biopsy status. Characteristics
Negative PSLN (N ¼ 210)
Positive PSLN (N ¼ 17)
p-Value
Age Gender Male Female Tumor location LE Trunk Breslow Thickness (mm) Average Ulceration Yes No Mitotic rate <1/mm2 1/mm2 Regression Yes No LVI Yes No Tumor subtype SS Nodular AL Other
55.8 ± 16.3
56.1 ± 15.9
0.943a
78 (37%) 132 (63%)
13 (76%) 4 (24%)
0.003b
173 (82%) 37 (18%)
13 (76%) 4 (24%)
0.518c
1.6 (1.1e2.6)
2.6 (1.9e6)
0.002d
55 (31%) 120 (69%)
7 (44%) 9 (56%)
0.466b
24 (24%) 77 (76%)
1 (11%) 8 (89%)
0.681c
13 (13%) 87 (87%)
0 (0%) 6 (100%)
1.000c
10 (10%) 87 (90%)
2 (33%) 4 (67%)
0.144c
25 (14%) 18 (10%) 20 (11%) 117 (65%)
2 4 3 4
0.021c
(15%) (31%) (23%) (31%)
x ± x indicates mean ± standard deviation; x.x (x.x e x.x) indicates median and inter-quartile range. PSLN: pelvic sentinel lymph node; LE: lower extremity; LVI: lymphovascular invasion; SS: superficial spreading; AL: acral lentiginous. Unknown values not represented in table and excluded from statistical analysis. a Student's t-test (two-sided). b Pearson's chi-squared test. c Fisher's exact test. d Wilcoxon rank-sum test with continuity correction.
Please cite this article in press as: Schuitevoerder D, et al., Is pelvic sentinel node biopsy necessary for lower extremity and trunk melanomas?, The American Journal of Surgery (2017), http://dx.doi.org/10.1016/j.amjsurg.2017.03.028
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D. Schuitevoerder et al. / The American Journal of Surgery xxx (2017) 1e5
dissection is performed in addition to inguinal node dissection for positive SSLN, we would be over-treating >70% of pelvic nodes. Thus, in the face of both inguinofemoral and pelvic sentinel nodes one might consider frozen section of the inguinofemoral sentinel node; if that node is negative there is no need for further PSLN biopsy (based on our finding of a NPV of 99%), however, if that node is positive one could consider performing PSLN biopsy to determine whether completion lymph node dissection of that basin is necessary. A similar approach has been to use the status of Cloquet's node during inguinofemoral dissection to determine the status of the pelvic nodes. However, variability in drainage patterns and low rates of disease involvement of this node has led some to question the reliability of this approach.20,21 In our study we found male sex, tumor thickness, and melanoma subtype to be predictive of positive PSLNs. However, given the small number of cases with a positive PSLN, 17, it is difficult to draw definitive conclusions from this data, and these findings should not influence the decision to perform PSLN biopsy. In the setting of both SSLN and PSLN biopsy, a negative SSLN was found to be an accurate and robust predictor of the absence of disease in the PSLN (NPV 99%). Out of the 152 such cases, 1 (0.7%) had a positive PSLN, the remainder were negative. This finding is in keeping with other studies that showed a 1e2.5% rate of pelvic lymph node recurrence after negative SSLN biopsy.15,22 Similarly, in a recent publication by Miranda et al., of 86 cases with drainage to both SSLNs and PSLNs, 74 had negative a SSLN biopsy. In all of these cases the PSLN was also negative.23 In 2476 cases of primary lower extremity and trunk cutaneous melanomas there were 227 cases of PSLNs identified (9%). This is similar to the 8% incidence found by van der Ploeg et al.,4 but considerably lower than the 23% described by Karakousis et al.5 The discrepancy here may be explained by the fact that in the study by Karakousis et al. the majority of cases had weaker tracer uptake in pelvic nodes and thus those nodes were often considered secondechelon, while ours represented the true sentinel node. Of the 227 cases of drainage to PSLNs, 46 (20%) drained exclusively to this basin without sentinel nodes identified in the inguinofemoral region. Of these, 39 were from LE primaries and 7 were from primary tumors of the trunk. This finding goes against the traditional dogma that pelvic nodes are considered second order, but is supported by other studies demonstrating similar lymphatic drainage patterns.6,7 Nevertheless out of these 46 cases of isolated pelvic sentinel node drainage, 8 (17%) were positive for metastatic disease, highlighting the need to perform SLNB in this situation. Furthermore we found PSLN biopsy to be safe with an equivalent complication rate to SSLN biopsy (15 vs 14% respectively). This finding is supported by a recent study by Chang et al. looking at postoperative complication rates for inguinofemoral node dissection. In their study the addition of pelvic node dissection did not significantly increase the risk of wound complications.24 5. Conclusions In conclusion, we found PSLN biopsy to be safe, with an equivalent complication rate to SSLN biopsy. The fact that 20% of cases with PSLNs identified did not have drainage to SSLN challenges the traditional teaching that lower extremity melanoma always drains in a stepwise fashion and warrants consideration when dealing with this disease process. In this situation, isolated pelvic nodes should be biopsied in order to provide accurate staging. However, in the face of drainage to both SSLNs and PSLNs, the finding of negative SSLNs almost always predicted negative PSLNs. Thus performing routine PSLN biopsy appears to hold minimal clinical impact. Given the poor PPV of SSLNs, in the setting of positive SSLNs, PSLN biopsy could be used to determine which patients
would benefit from pelvic node dissection. Therefore, we would recommend PSLN biopsy when the SSLNs are positive or when the tumor drains only to pelvic nodes. Conflict of interest None. References 1. Network NCC. Melanoma. https://www.nccn.org/professionals/physician_gls/ pdf/melanoma.pdf. Accessed Oct. 29th, 2016. 2. Nieweg OE, Tanis PJ, Kroon BB. The definition of a sentinel node. Ann Surg Oncol. 2001;8(6):538e541. 3. Balch CM, Gershenwald JE, Soong SJ, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol Of J Am Soc Clin Oncol. 2009;27(36): 6199e6206. 4. van der Ploeg IM, Kroon BB, Valdes Olmos RA, Nieweg OE. Evaluation of lymphatic drainage patterns to the groin and implications for the extent of groin dissection in melanoma patients. Ann Surg Oncol. 2009;16(11): 2994e2999. 5. Karakousis GC, Pandit-Taskar N, Hsu M, et al. Prognostic significance of drainage to pelvic nodes at sentinel lymph node mapping in patients with extremity melanoma. Melanoma Res. 2013;23(1):40e46. 6. Everett M, Gutman H. Lymphatic drainage of calf melanoma skipping the superficial groin. Lymphat Res Biol. 2007;5(4):265e268. 7. Miura H, Ono S, Nagahata M, et al. Lymphoscintigraphy for sentinel lymph node mapping in Japanese patients with malignant skin neoplasms of the lower extremities: comparison with previously investigated Japanese lymphatic anatomy. Ann Nucl Med. 2010;24(8):601e608. 8. Egger ME, Brown RE, Roach BA, et al. Addition of an iliac/obturator lymph node dissection does not improve nodal recurrence or survival in melanoma. J Am Coll Surg. 2014;219(1):101e108. 9. Glover AR, Allan CP, Wilkinson MJ, Strauss DC, Thomas JM, Hayes AJ. Outcomes of routine ilioinguinal lymph node dissection for palpable inguinal melanoma nodal metastasis. Br J Surg. 2014;101(7):811e819. 10. Niebling MG, Wevers KP, Suurmeijer AJ, van Ginkel RJ, Hoekstra HJ. Deep lymph node metastases in the groin significantly affects prognosis, particularly in sentinel node-positive melanoma patients. Ann Surg Oncol. 2015;22(1): 279e286. 11. Glumac N, Hocevar M, Zadnik V, Snoj M. Inguinal or inguino-iliac/obturator lymph node dissection after positive inguinal sentinel lymph node in patients with cutaneous melanoma. Radiol Oncol. 2012;46(3):258e264. 12. Emery RE, Stevens JS, Nance RW, Corless CL, Vetto JT. Sentinel node staging of primary melanoma by the “10% rule”: pathology and clinical outcomes. Am J Surg. 2007;193(5):618e622. discussion 622. 13. R Core Team. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing; 2013. ISBN 3-900051-07-0. Available at: http://www.R-project.org. 14. Cochran AJ, Balda BR, Starz H, et al. The Augsburg Consensus. Techniques of lymphatic mapping, sentinel lymphadenectomy, and completion lymphadenectomy in cutaneous malignancies. Cancer. 2000;89(2):236e241. 15. Soteldo J, Ratto EL, Gandini S, et al. Pelvic sentinel lymph node biopsy in melanoma patients: is it worthwhile? Melanoma Res. 2010;20(2):133e137. 16. Mozzillo N, Pasquali S, Santinami M, et al. Factors predictive of pelvic lymph node involvement and outcomes in melanoma patients with metastatic sentinel lymph node of the groin: a multicentre study. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol. 2015;41(7):823e829. 17. Allan CP, Hayes AJ, Thomas JM. Ilioinguinal lymph node dissection for palpable metastatic melanoma to the groin. ANZ J Surg. 2008;78(11):982e986. 18. Zdzienicki M, Rutkowski P, Nowecki ZI, et al. The analysis of the outcomes and factors related to iliac-obturator involvement in cutaneous melanoma patients after lymph node dissection due to positive sentinel lymph node biopsy or clinically detected inguinal metastases. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol. 2013;39(3):304e310. 19. Chu CK, Delman KA, Carlson GW, Hestley AC, Murray DR. Inguinopelvic lymphadenectomy following positive inguinal sentinel lymph node biopsy in melanoma: true frequency of synchronous pelvic metastases. Ann Surg Oncol. 2011;18(12):3309e3315. 20. Teramoto Y, Nakamura Y, Sato S, Yamazaki N, Yamamoto A. Low probability of lymphatic drainage to Cloquet's node is of limited value as indicator for pelvic lymph node dissection in patients with lower limb melanoma. Lymphat Res Biol. 2016;14(2):109e114. 21. Chu CK, Zager JS, Marzban SS, et al. Routine biopsy of Cloquet's node is of limited value in sentinel node positive melanoma patients. J Surg Oncol. 2010;102(4):315e320. 22. Essner R, Scheri R, Kavanagh M, Torisu-Itakura H, Wanek LA, Morton DL. Surgical management of the groin lymph nodes in melanoma in the era of sentinel lymph node dissection. Arch Surg. 2006;141(9) (Chicago, Ill: 1960) 877-882; discussion 882e874. 23. Miranda SG, Parrett BM, Li RR, et al. Selective sentinel lymph node dissection in lower extremity melanoma. Plastic Reconstr Surg. 2016;137(3):1031e1038.
Please cite this article in press as: Schuitevoerder D, et al., Is pelvic sentinel node biopsy necessary for lower extremity and trunk melanomas?, The American Journal of Surgery (2017), http://dx.doi.org/10.1016/j.amjsurg.2017.03.028
D. Schuitevoerder et al. / The American Journal of Surgery xxx (2017) 1e5 24. Chang SB, Askew RL, Xing Y, et al. Prospective assessment of postoperative complications and associated costs following inguinal lymph node dissection (ILND) in melanoma patients. Ann Surg Oncol. 2010;17(10):2764e2772.
Discussion: Vance Sohn, MD; Gig Harbor, WA I would like to thank Drs Schuitevoerder and Vetto on their work entitled “Is Pelvic Sentinel Node Biopsy Necessary for Lower Extremity and Trunk Melanomas?” In their retrospective analysis of a multi-institutional melanoma database, the authors challenge the notion that lymphatic spread for melanoma occurs in an orderly, step wise fashion, the so called spectrum theory. The authors sought to identify the incidence of pelvic sentinel lymph nodes, define the correlation between superficial and pelvic sentinel nodes, and to determine the clinical impact of pelvic sentinel lymph nodes. Over a 23 year experience, 227 of the 2476 clinically node negative lower extremity and truncal melanomas that underwent pelvic sentinel node sampling comprised the study cohort. Of the 227, 181 had both pelvic and superficial nodal drainage and 46 had only pelvic drainage. These 46 patients are the most interesting to me, with 39 patients who had lower extremity melanoma with only deep groin nodes. A notable conclusion of their findings was that 20% of cases with pelvic sentinel lymph nodes did not have drainage to the superficial nodal basin and therefore. Furthermore, the authors suggest that if there are both superficial and pelvic sentinel nodes, but the superficial node is negative, then the need
5
for a deep node biopsy is obviated. I would like to congratulation the authors on addressing an interesting, albeit unusual, clinical issue. My questions include: 1. Based on my own personal experience, I imagine that SLN sampling, particularly for lower extremity melanomas, is grossly underestimated and underperformed by most oncologic surgeons. Certainly for truncal melanomas that have variable drainage patterns, pre-operative mapping is essential; however, for most lower extremity melanomas, routine mapping is not performed. In light of the recommendation that routine Stage III cancers do not undergo routine pre-operative imaging unless indicated, how are pelvic nodes identified pre-operatively1? At your institution, who gets pre-operative lymphoscintography? 2. The study period encompasses patients who were enrolled starting 1993 and yet, Dr Morton first described the technique for melanoma first at the SSO in 1990.2 During your analysis, did the era of the diagnosis, especially when sentinel node sampling was in it's infancy, affect any of your findings? 3. I am curious to hear the authors perspectives on how these findings may alter the NCCN recommendations regarding a deep pelvic lymphadenectomy. Again, congratulations on an interesting paper.
1 NCCN Melanoma, https://www.nccn.org/professionals/physician_gls/pdf/ melanoma.pdf, Version1.2017, accessed 1 November 2016. 2 Morton D, Cagle L, Wong J, et al. Intraoperative lymphatic mapping and selective lymphadenectomy: technical details of a new procedure for clinical stage I melanoma. Presented at the Annual Meeting of the Society of Surgical Oncology; Washington, DC. 1990.
Please cite this article in press as: Schuitevoerder D, et al., Is pelvic sentinel node biopsy necessary for lower extremity and trunk melanomas?, The American Journal of Surgery (2017), http://dx.doi.org/10.1016/j.amjsurg.2017.03.028