Evolving treatment of locoregional metastatic melanoma
Faut, Marloes
DOI:
10.33612/diss.93011206
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Publication date:
2019
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Faut, M. (2019). Evolving treatment of locoregional metastatic melanoma. University of Groningen.
https://doi.org/10.33612/diss.93011206
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Marloes Faut Schelto Kruijff Harald J Hoekstra Robert J. van Ginkel Lukas B Been
Barbara L. van Leeuwen
Abstract:
Background: In recent years there has been a plea to abandon the pelvic lymph
node dissection in the treatment of patients with metastatic melanoma to the groin. A trend towards a conservative surgical treatment is already evolving in several European countries. The purpose of this study is to identify factors associated with pelvic nodal involvement, in order to improve selection of patients whom might benefit from a pelvic nodal dissection.
Methods: A retrospective analysis was performed on prospectively collected data
concerning patients who underwent an inguinal lymph node dissection (ILND) with pelvic lymph node dissection for metastatic melanoma at the University Medical Center Groningen. Multivariable logistic regression analysis was performed to determine factors associated with pelvic nodal involvement. Diagnostic accuracy was calculated for 18F-FDG PET + contrast enhanced CT-scan and 18F-FDG PET+low dose CT-scan.
Results: Two-hundred-and-twenty-six ILND’s were performed in 223 patients. The
most common histologic subtype was superficial spreading melanoma (42.6%). In patients with micrometastatic disease, 15.7% had pelvic nodal involvement vs 28.2% in patients with macrometastatic disease (p:0.030). None of the characteristics known prior to the ILND, were associated with pelvic nodal involvement. Imaging methods were unable to accurately predict pelvic nodal involvement. Negative predictive value was 78% for 18F-FDG PET+low dose CT-scan and 86% for an 18F-FDG PET+contrast enhanced CT-scan.
Conclusion: There are no patient- or tumour characteristics available that can
predict pelvic nodal involvement in patients with melanoma metastasis to the groin. As no imaging technique is able to predict pelvic nodal involvement it seems unjust to abandon the pelvic lymph node dissection.
Introduction:
Cutaneous melanoma mainly spreads via the lymphogenic route from the sentinel lymph nodes to the adherent lymph node basin. At the time of primary staging, approximately 20 % of melanoma patients are SLNB positive.1-3 In case of a palpable
or sentinel node positive metastatic melanoma to the lymph nodes, a lymph node dissection is standard of care. An inguinal lymph node dissection (ILND) is a surgical procedure associated with a complication rate of up to 50%.4-7 There are two anatomic
regions harboring lymph nodes in the groin, the superficial region which consist of lymph nodes in the femoral triangle, and the pelvic region which consists of lymph nodes along the external iliac artery and obturator region. Whether a combined dissection is imperative in case of superficial nodal involvement is not clear, as pelvic nodes are involved in only 13-15% of patients with micrometastatic disease to the groin.8,9 In the last decade there has been a large amount of publications focusing on
the pelvic part of the ILND, often insisting on abandoning this part of the dissection. This in order to reduce postoperative complications and morbidity. Data showing an association between the extent of the dissection and postoperative morbidity are however, ambiguous.10,11 In the currently ongoing EAGLE-FM (ClinicalTrials.
gov Identifier: NCT02166788) this possible difference in morbidity caused by the pelvic part of the lymph node dissection is studied. Results however, are not to be expected in the near future. Despite the ongoing debate, somewhat prematurely, a trend towards a more conservative surgical treatment is already evolving in some European countries.8,12,13 It is questionable if this conservative surgical attitude
towards a highly aggressive malignancy, such as melanoma, is justified. It remains crucial to rule out occult pelvic nodal involvement before minimizing the extent of the ILND. The purpose of this study is to identify factors associated with pelvic nodal involvement in patients with metastatic melanoma to the groin based on a large prospective dataset.
Material and methods
Patients who underwent a combined superficial and pelvic ILND (ilio-inguinal lymph node dissection) for stage III melanoma between 1989 and 2016 at the University Medical Center Groningen (UMCG) were prospectively included in a database. The UMCG is a tertiary melanoma referral centre in the northern part of the Netherlands. Data were collected concerning patient characteristics, tumour characteristics, nodal yield, size of the metastasis, extracapsular extension (ECE), recurrence and survival. In the early years of ILND’s, information about the number of lymph nodes harvested and size of largest metastasis was not always reported in the pathology reports. Patients with incomplete pathology reports were excluded from further analysis. Follow-up was conducted at the UMCG. Patients with micrometastatic as well as macrometastatic disease were treated with an ilioinguinal lymph node dissection. The surgical procedure has been extensively described in the methods section of previous studies.4,14
Statistical analysis was performed with IBM SPSS version 22.0 (IBM, inc, Chicago, IL, USA). Differences between continuous variables were analysed with the one-way ANOVA or the Mann Whitney U. Differences between nominal variables were analysed using Chi square. Melanoma specific survival (MSS) and disease free survival (DFS) were calculated with a Kaplan-Meier analysis. MSS and DFS were compared between patients with and patients without pelvic nodal involvement and between patients whom underwent a completion lymph node dissection (CLND) or therapeutic lymph node dissection (TLND) and tested for significance with log rank. Patients lost to follow-up were entered in the DFS analysis, if the first recurrence had occurred before patients were lost to follow-up. They were excluded from the MSS analysis.
The following variables were analysed for a potential association with pelvic nodal involvement: sex, age at ILND, histological subtype, Breslow thickness, the presence of ulceration, location of primary, indication (macro-/microscopic metastasis), nodal yield (superficial and total), largest lymph node (LN) metastasis and the presence of extracapsular extension. The expected nodal yield for a superficial dissection is 8-10 LN’s and for the pelvic dissection 4-6 LN’s.15 The total nodal yield was entered as a
categorical variable (0-16 LN’s, 17-22 LN’s and >22 LN’s). The superficial nodal yield was also entered as a categorical variable (<8 LN’s, 8-10 LN’s, >10 LN’s). Variables on a 20% significance level in the univariate logistic regression were entered in the multivariable logistic regression. Variables with a p<0.05 in the multivariable logistic regression were identified as significant factors associated with pelvic nodal involvement. Diagnosis leading to dissection and total nodal yield were not included in the analysis due to their correlation with size of the largest metastasis and superficial nodal yield, respectively.
Metastasis found with a sentinel lymph node biopsy were defined as microscopic metastasis. Metastasis that were clinically evident were defined as macroscopic metastasis.
Imaging used to diagnose metastasis prior to TLND could be either computed tomography (CT), fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) with a low dose CT-scan or a 18F-FDG PET with a contrast enhanced
CT-scan. Results of this imaging method were used for the calculation of positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity. PPV was calculated as: true positive/(true positive + false positive), NPV was calculated as: true negative/(true negative + false negative), sensitivity was calculated as: true positive/(true positive + false negative) and specificity was calculated as: true negative/(false positive + true negative). Due to the low prevalence, none of these calculations were made for CT-scan. Recurrences were defined as follows: In transit metastasis and recurrence at primary site were defined as locoregional recurrence, recurrences in the nodal basin were defined as lymphatic. All distant recurrences were defined as distant.
The primary endpoint was pelvic lymph node involvement as proven by histopathological and/or cytological examination. Secondary endpoints were MSS and DFS in patients with pelvic nodal involvement. As well as the diagnostic accuracy of the different imaging modalities used to diagnose pelvic nodal involvement. Institutional review board approval was obtained and the study was conducted according to the declaration of Helsinki.
Results:
A total of 262 ilio-inguinal LND’s were performed in 259 patients between 1989 and May 2016. Median age was 57.4 (5.9-91.1) years, 53.4% were female and 46.6% were male. Three ilio-inguinal LND’s were combined with an isolated limb perfusion. In 36 patients, data concerning nodal yield and size of metastasis were incomplete, these patients were excluded. The analyses were thus performed on 226 ilio-inguinal LND’s in 223 patients. Baseline patient and tumor characteristics are displayed in Table 1. Thirty-two percent of the patients underwent an ilio-inguinal lymph node dissection due to micrometastatic disease and the remaining 68% due to macrometastatic disease. The most common histologic subtype was superficial spreading melanoma (SSM) 42.6% , followed by nodular melanoma (NM) 20.6% and acrolentigenous melanoma (ALM) 9.4%. Median Breslow thickness was 2.5 range (0.4-27) mm. A total of 33 patients were lost to follow-up.
In patients with micrometastatic disease, 15.7% had pelvic nodal involvement and in patients with macrometastatic disease this was 28.2% (p:0.030). In patients with pelvic nodal involvement the median size of the largest metastasis found in the dissected specimen was higher, 30mm (range 1.5-70) vs 22mm (range 0.2-95)( p:0.047) and the number of positive nodes was also higher 5 (range 1-36) vs 1 (range 0-17) (p:<0.001). Extracapsular extension was found more frequently (p:0.016) in the pathology specimen of the patients with pelvic nodal involvement (Table 2).
Table 1 Baseline characteristics
Char
acteristic
Baseline (n=223)
Without pelvic involv
ement (n=168) With pelvic in volv ement (n=55) p: n % Median Range n % median (r ange ) n % median (r ange ) Gender 0.840 Male 104 46.6 79 47 25 45.5 Female 119 53.4 89 52.9 30 54.5 Age, in y ears a 57.4 5.9-91.1 56.9 (5.9-89.1) 60 (20.2-91.1) 0.622
Localization of primary tumor
0.913 Trunk 26 11.7 21 12.5 5 9.1 Genital area 4 1.8 3 1.8 1 1.8 Thigh 60 26.9 47 28 13 23.6 Lower leg 76 34.1 54 32.1 22 40 Foot 42 18.8 32 19 10 18.2 Unknown primary 15 6.7 11 6.5 4 7.3 Histology of primary 0.308 Superficial spreading 95 42.6 72 42.9 23 41.8 Nodular melanoma 46 20.6 35 20.8 11 20 Acr al lentigenous 21 9.4 18 10.7 3 5.5 Other b 19 8.5 16 9.5 3 5.5 Unknown 42 18.8 27 16.1 15 27.3
Breslow thickness 2.5 0.4-27.0 2.5 (0.4-27.0) 2.5 (0.60-15) 0.918 T1: ≤1.00 19 8.5 12 7.1 7 12.7 0.268 T2:1.01-2.00 60 26.9 47 28 13 23.6 T3: 2.01-4.0 74 33.2 61 36.3 13 23.6 T4: >4.0 51 22.9 35 20.8 16 29.1 Ulcer ation 0.193 Ye s 80 35.9 62 36.9 18 32.7 No 110 49.3 88 52.4 22 40
a: age at ILND b: Other histological typings ar
e: v
Table 2 Results of the lymph node dissection Baseline (n=223) Without pelvic in volv ement (n=171) With pelvic in volv ement (n=55) n % Median Range n % median (r ange ) n % median (r ange ) Indication 0.030 Micrometastasis 72 32 61 35.7 11 20 Macrometastasis 154 68 110 64.3 44 80
Metastasis found in the ILND
Ye s 169 74.8 No 57 25.2 Nodal yield 15 1-44 15 (1-38) 17 (5-44) 0.110 0-16 132 58.4 105 61.4 27 49.1 0.270 17-22 58 25.7 41 24 17 30.9 >22 36 15.9 25 14.6 11 20 Largest metastasis 30 (1.5-70) 0.047 ≤1 mm 31 13.7 31 18.1 0 1.01-10 mm 33 14.6 25 14.6 8 14.5 10.01-40 mm 90 39.8 62 36.3 28 51 >40.01 mm 36 15.9 24 14 12 21.8
Superficial nodal yield
25 0.2-95 22 (0.2-95) 0.247 <8 68 30.1 48 28.1 20 36.4 8-10 64 28.3 53 31 11 20 >10 94 41.6 70 40.9 24 43.6
Number of positiv e nodes (sup ) 1 (0.0-17) 2 (0-30) <0.001 0 60 26.5 53 31 7 12.7 1-3 126 55.8 98 57.3 28 51 ≥ 4 40 17.7 20 11.7 20 36.4 Extr acapsular e xtension 0.016 Ye s 73 32.3 48 28.1 25 45.5 No 153 67.7 123 71.9 30 54.5 P elvic in volv ement Ye s 55 24.3 No 171 75.7
During the current median follow-up of 26.1 (range 0.16-234) months, 60.1% of patients experienced a recurrence. Differences between patients with and without pelvic nodal involvement are displayed in Table 3. Recurrences (p:0.001) were diagnosed more frequently in the pelvic nodal involvement group. There was no significant difference in site of first recurrence. In the group without pelvic nodal involvement two out of nine recurrences involved the pelvic bed, the remaining recurrences were superficial. In the group with pelvic nodal involvement, lymphatic recurrences occurred only in the superficial region.
Table 3 Recurrences
Baseline (n=223) Without pelvic
involvement (n=171) With pelvic involvement (n=55)
n % n % n % p
Recurrence 0.001
Yes 134 60.1 94 54.9 40 72.7
No 68 30.5 59 34.5 9 16.4
n.a. palliative dissection 3 1.3 - 3 5.5
Lost to follow-up 18 8.1 15 8.8 3 5.5
Type Recurrence 0.319
Locoregional 41 18.4 31 18.1 10 18.2
Lymphatic 11 4.9 9 5.3 2 3.6
Distant 83 37.2 54 31.6 28 50.9
Multivariable logistic regression revealed that the presence of more than four superficial nodal metastases was associated with the occurrence of pelvic nodal metastatic disease (HR10.31, p:0.005). None of the baseline patient or tumor characteristics were associated with the occurrence of pelvic nodal involvement (Table 4).
Table 4 Univariate and multivariable analysis of factors associated with pelvic nodal involvement.
Characteristic Pelvic nodal
involvement Univariate Overall MultivariableOverall
n/55 HR, p HR, p (95% CI)
Sex
Male 25 0.93, 0.805
Female 30
Agea, median (range) 60 (20.2-91.1) 1.01, 0.587 Histologic subtype SSM 23 1.00, 0.314 NM 11 0.94, 0.890 ALM 3 0.53, 0.340 Otherb 3 0.60, 0.441 Unknown 15 1.76, 0.157 Breslow thickness T1: ≤1.00 7 1.00, 0.282 1.00, 0.304 T2:1.01-2.00 13 0.46, 0.166 0.53, 0.464 (0.10-2.88) T3: 2.01-4.0 13 0.37, 0.075 0.20, 0.075 (0.03-1.18) T4: >4.0 16 0.76, 0.629 0.41, 0.342 (0.07-2.58) Location of primary Trunk 5 1.00, 0.894 Genital area 1 1.53, 0.734 Thigh 13 1.27, 0.680 Lower leg 22 1.84, 0.271 Foot 10 1.44, 0.553 Unknown primary 4 1.67, 0.501 1.83, 0.175 (0.76-4.36) Ulceration present 18 1.44, 0.129 Indication Micrometastasis 11 Macrometastasis 44 2.11, 0.046 Nodal yield 0-16 27 1.00, 0.274 17-22 17 1.61, 0.185 >22 11 1.71, 0.202
Superficial nodal yield
<8 20 1.00, 0.253 1.00, 0.097
8-10 11 0.50, 0.101 0.27, 0.032 (0.08-0.90)
Largest metastasis categorical ≤1 mm 0 1.01-10 mm 8 1.00, 0.020 1.00, 0.930 10.01-40 mm 28 3.16, 0.009 0.95, 0.937 (0.29-3.14) >40.01 mm 12 3.50, 0.015 1.16, 0.833 (0.29-4.73) Number of positive superficial nodes 0 7 1.00, <0.001 1.00, 0.010 1-3 28 2.16, 0.090 2.89, 0.125 (0.74-11.19) ≥ 4 20 7.57, <0.001 10.31, 0.005 (2.04-52.08) Extracapsular extension present 25 2.14, 0.018 1.84, 0.189 (0.74-4.54) a: age at ILND
b: Other histological typings are: verrucus, spitzoid, epitheloid, desmoplastic melanoma and Lentigo Maligna Melanoma.
Median melanoma specific survival (MSS) for the entire cohort was 44.4 (range 0.92-234) months. In patients with pelvic nodal involvement median MSS was 22.7 (range 2.6-234) months compared to a median of 76.3 (range 0.92-223.4) months in patients without pelvic nodal involvement (p:<0.001). In patients who underwent a completion lymph node dissection (CLND), median MSS was significantly worse if pelvic nodes were involved; 31.8 (range 9.2-88.8) months compared to 144.2 (range 6.3-217.6) if no pelvic nodes were involved (p:0.001). In patients whom underwent a therapeutic lymph node dissection (TLND), median MSS was also significantly worse if pelvic nodes were involved; 18.1 (range 2.6-234) months compared to 43.2 (range 0.92-223.4) if no pelvic nodes were involved (p:0.001) (Figure 1). Median DFS for the entire cohort was 17.2 (range 0.26-234) months. In patients with pelvic nodal involvement, median DFS was 8.7 (range 1.11-234) months compared to a median of 22.0 (range 0.26-223.4) months in patients without pelvic nodal involvement (p:<0.001) (Figure 2).
Figure 1: Melanoma specific survival for all ILND patients
A: MSS: Median 44.4 (range 0.92-234) months.
B: Green: MSS for patients with pelvic nodal involvement, median 22.7 (range 2.6-234) months. Blue: MSS for patients without pelvic nodal involvement, median 76.3 (range 0.92-223.4) months, p:<0.001.
Figure 2: Disease free survival for all ILND patients. A: DFS: Median 17.1 (range 0.26-234) months.
B: Green: DFS for patients with pelvic nodal involvement, median 8.7 (range 1.11-234 ) months. Blue: DFS for patients without pelvic nodal involvement, median 22.0 (range 0.26-223.4 ) months, p:<0.001.
In the 153 of 154 patients with macrometastatic disease, imaging was performed prior to the TLND. In 37 patients (24%) this was insufficient (i.e. ultrasound, chest X-ray) to diagnose pelvic nodal involvement. Of the remaining 116 patients, a CT-scan was performed in 4 patients (2.6%), an 18F-FDG PET with a low dose CT-scan
in 83 patients (53.9%) and an 18F-FDG PET with a contrast enhanced CT-scan in 29 patients (18.8%).
A review was performed to compare predictors for pelvic nodal involvement in the literature to those in the UMCG series, as well as the diagnostic accuracy of the different imaging methods and is shown in Table 5.
Table 5 Ov
erview of the liter
ature (supplementary data)
Author Y ear Type P opulation N P elvic nodal in volv ement CLND (%) P elvic nodal in v olv ement TLND (%)
Predicting factors for pelvic nodal involv
ement
CT
-scan
18F-FDG PET + low dose CT
-scan 18F-FDG PET + contr ast enhanced CT -scan This series 2016 retrospectiv e CLND + TLND 226 15.7 28.2 ≥4 positiv e
superficial lymph nodes
n.a. PPV 75% NPV 78% Sens 48% Spec 92% PPV 57% NPV 86% Sens 57% Spec 86% Hughes et al 16 2000 retrospectiv e TLND 72 -40
Increasing no. of positiv
e superficial nodes PPV 100% NPV 66% Sens 45% Spec 100% n.a. n.a. Badgwell et al 17 2007 retrospectiv e CLND + TLND 97 -Age 50 y ears or older , no. of positiv e superficial nodes, r adiologic suspicion PPV 84% NPV - Sens 50% Spec 91% n.a. n.a. V an der Ploeg et al 12 2011 retrospectiv e TLND 121 -24.8 n.a. PPV 59% NPV 91% Sens 71% Spec 85% n.a. n.a. Chu et al 18 2011 retrospectiv e CLND 42 11.9 -≥3 positiv e
superficial nodes, lymph node r
atio >0.2 n.a. n.a. n.a. Z dzienicki et al 8 2013 retrospectiv e CLND + TLND 390 15 27.5 Type of LND ,
higher Breslow thickness, extr
acapsular
extension, male gender
n.a. n.a. n.a. Niebling et al 9 2014 retrospectiv e CLND + TLND 129 13 31 >3 positiv e
superficial lymph nodes
n.a. n.a. n.a. Oude Ophuis et al 13 2015 retrospectiv e TLND 209 -35 P ositiv e imaging, no. of positiv e
superficial nodes, lymph node r
atio, extr acapsular extension PPV 80% NPV 83% Sens 57% Spec 93% PPV 68% NPV 79% Sens 61% Spec 83% n.a.
Discussion:
This retrospective study is the second largest series in the current literature aiming to detect risk factors for pelvic nodal involvement in stage III melanoma patients, and the largest to compare findings of imaging methods to outcome. Pelvic nodal involvement is significantly more frequent in patients with macrometastatic disease compared to patients with micrometastatic disease, 28.2% vs 15.7% respectively. But more importantly, pre-operative characteristics other than palpable nodal disease are unable to predict pelvic nodal involvement after ILND in this large single center cohort. This retrospective study also reveals that in case of pelvic nodal involvement, survival is worse. In patients with pelvic nodal involvement, still one-third to a quarter can be cured by surgical treatment.
In one out of seven patients with microscopic nodal disease, pelvic nodes were involved. In patients with macrometastasis, pelvic nodal involvement was encountered in almost one third of all cases. If pelvic nodes are involved, the number of positive superficial nodes is higher and the presence of extra capsular extension is more frequent. This has all been well described in the literature.8,9,13 These
unfavorable characteristics are an expression of the melanomas biological aggressive behavior, as is pelvic nodal involvement. In a previous analysis of a smaller cohort from the same center, pre-operative tumor characteristics were unable to predict pelvic nodal involvement, confirming our current findings.9 A retrospective analysis
recently performed by Oude Ophuis et al. on a multicenter cohort, revealed that a combination of negative imaging, low number of positive superficial nodes, absence of extra capsular extension and low lymph node ratio was able to predict the absence of pelvic nodes in 84% of patients.13 This however implies that 16% of all patients
undergoing a inguinalLND only, received an insufficient, potential curative surgical treatment. The required characteristics in the proposed model, are unknown prior to the ILND, leaving the treating physician clueless on whether to perform an inguinal lymph node dissection, or an ilio-inguinal lymph node dissection.
As displayed in the overview of the literature in Table 5, besides radiologic imaging and clinically evident nodal disease, there are no other characteristic prior to the ILND, predictive of pelvic nodal involvement.
With advancements made in imaging methods over the last years, perhaps pelvic nodal involvement can be accurately predicted by the different imaging methods. In the past, a fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG
PET) with low dose CT-scan was performed at the UMCG in case of clinically evident nodal disease to the groin, to rule out distant disease. The current study showed that with a PPV of 75% and a NPV of 78% this imaging methods are insufficient to diagnose pelvic nodal involvement prior to the ILND. The current imaging method is an 18F-FDG-PET combined with a diagnostic contrast-enhanced CT scan to rule
out distant disease. As reported in this series, the PPV of 57% and NPV of 86% are disappointing and insufficient to diagnose pelvic nodal involvement. The sensitivity of an 18F-FDG PET has been reported to be 92.7%- 94.2% for detecting melanoma metastasis.19,20 If an 18F-FDG PET is used for nodal staging only, sensitivity decreases
to 17% if metastasis are smaller than 3mm.21,22 Sensitivity of CT-scan alone has been
reported to be 71% in patients with macrometastatic disease.12
Survival was significantly worse if pelvic nodes were involved (median MSS 31.8 vs 144.2 months) compared to patients without pelvic nodal involvement. These survival data are also confirmed in the case of clinically palpable disease to the groin.8,12,16
Adjuvant treatment for high risk stage III melanoma improves disease free and overall survival.23 Therefore it seems even more important to rule out pelvic nodal
involvement, as patients with pelvic nodal involvement could be classified as high risk stage III melanoma that might benefit from adjuvant immunotherapy in the future. The concept of a wait and see policy was introduced in order to prevent possible overtreatment. With the results of the MSLT-II trial, it is clear that survival is not affected by a delayed CLND.12,24-27 It is important to realize however, that timing of
surgery is not to be confused with the extent of surgery. As survival is not affected by a delayed CLND after a positive SLNB, the discussion evolving around the extent
of the dissection is even more important. As in current times, with the availability of effective systemic treatments for metastatic melanoma such a BRAF-inhibitors and immunotherapy28,29 a trend towards a conservative surgical therapy and a progressive
systemic therapy in the treatment of metastatic melanoma is evolving. Authors suggesting a conservative surgical approach neglect the potential consequences of abandoning (the pelvic part of) the ILND.8,12,13 Abandoning surgical treatment
in stage III melanoma and replacing it with systemic therapy would lead to an overtreatment of approximately 50% of patients in this study that will never develop stage IV melanoma. As described above, no diagnostic tool is available to help select patients with potential pelvic nodal involvement and thus a worse prognosis. Taking other factors such as side effects, response rates and costs of systemic therapy into account, it seems premature to determine systemic treatment of stage III melanoma as standard of care.
In our opinion pelvic nodes should always be resected during an ILND, until conclusive evidence is provided that leaving occult metastatic disease to the pelvic lymph nodes untreated, does not affect prognosis. In light of the recently published results of the MSLT-II trial, CLND might not be standard of care in the future.27 Should a positive
SLNB be followed by a CLND, this dissection should involve both the inguinal and iliac basin.
There is no conclusive evidence that an ilio-inguinal lymph node dissection increases postoperative morbidity compared to an inguinalLND.2,16 The contradictory data
on this suggest, that if there is a difference, the difference in morbidity is small. In the current ongoing EAGLE-FM trial (ClinicalTrials.gov Identifier: NCT02166788) this possible difference in morbidity caused by the pelvic lymph node dissection is studied. As long as results are awaited, it seems premature to abandon the pelvic part of the lymph node dissection based on a gut feeling. Therefore for now, morbidity should be considered as a sophism in determining whether the pelvic part of the ILND should be abandoned.
To resume, even anno 2016 the discussion evolving around the necessity of the ILND in metastatic melanoma to the groin and more specifically the pelvic part of the ILND
has not yet come to an end. As long as no selection tool exists accurate enough to predict pelvic nodal involvement prior to the ILND, it does not seem just to omit the pelvic lymph node dissection outside a trial. Especially since survival is highly affected by the presence of pelvic metastatic nodes.
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