Radiol Oncol 2021; 55(1): 50-56. doi: 10.2478/raon-2020-0056
50
research article
Completely resected stage III melanoma 
controversy - 15 years of national tertiary 
centre experience 
Barbara Peric1,2, Sara Milicevic1, Andraz Perhavec1,2, Marko Hocevar1,2,3, Janez Zgajnar1,2
1 Department of Surgery, Institute of Oncology Ljubljana, Ljubljana, Slovenia
2 Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
3 Faculty of Medicine, University of Maribor, Maribor, Slovenia
Radiol Oncol 2021; 55(1): 50-56.
Received 28 May 2020 
Accepted 24 July 2020
Correspondence to: Assist. Prof. Barbara Perić, M.D., Ph.D., Institute of Oncology Ljubljana, Zaloška 2, SI-1000 Ljubljana, Slovenia. E-mail: 
bperic@onko-i.si
Disclosure: No potential conflicts of interest were disclosed. 
Background. Two prospective randomized studies analysing cutaneous melanoma (CM) patients with sentinel 
lymph node (SLN) metastases and rapid development of systemic adjuvant therapy have changed our approach to 
stage III CM treatment. The aim of this study was to compare results of retrospective survival analysis of stage III CM 
patients’ treatment from Slovenian national CM register to leading international clinical guidelines.
Patients and methods. Since 2000, all Slovenian CM patients with primary tumour ≥ TIb are treated at the Institute 
of Oncology Ljubljana and data are prospectively collected into a national CM registry. A retrospective analysis of 
2426 sentinel lymph node (SLN) biopsies and 789 lymphadenectomies performed until 2015 was conducted using 
Kaplan-Meier survival curves and log-rank tests.  
Results. Positive SLN was found in 519/2426 (21.4%) of patients and completion dissection (CLND) was performed 
in 455 patients. The 5-year overall survival (OS) of CLND group was 58% vs. 47% of metachronous metastases group 
(MLNM) (p = 0.003). The 5-year OS of patients with lymph node (LN) metastases and unknown primary site (UPM) was 
45% vs. 21% of patients with synchronous LN metastasis. Patients with SLN tumour burden < 0.3 mm had 5-year OS 
similar to SLN negative patients (86% vs. 85%; p = 0.926). The 5-year OS of patients with burden > 1.0 mm was similar to 
the MLNM group (49% vs. 47%; p = 0.280). 
Conclusions. Stage III melanoma patients is a heterogeneous group with significant OS differences. CLND after posi-
tive SLNB might still remain a method of treatment for selected patients with stage III. 
Key words: cutaneous melanoma; sentinel node biopsy; completion lymph node dissection; overall survival
Introduction
Since Morton has introduced the concept of senti-
nel lymph node (SLN) biopsy, the procedure had 
been a central part of cutaneous melanoma (CM) 
treatment. The information about SLN metastases 
is considered as one of the most important indica-
tors of recurrence and survival of CM patients.1,2 
Completion lymph nodes dissection (CLND) was 
offered to patients with positive SLN despite sig-
nificant morbidity which is only slightly lower in 
case of CLND compared to therapeutic lymphad-
enectomy.3 Common belief was that at least 20% of 
patients with positive non-SLN would benefit from 
that kind of treatment.4 
Despite all attempts to prove otherwise, two 
prospective randomised studies conducted in re-
cent years have shown that CLND does not im-
prove survival of patients with positive SLN com-
pared to follow up of the nodal basin with ultra-
sound (US).5,6 
Although there was no significant improvement 
of overall survival (OS), the MSLT-2 study did in-
dicate, that immediate CLND offers better regional 
Radiol Oncol 2021; 55(1): 50-56.
Peric B et al. / Resected stage III melanoma controversy 51
control and that non-SLN burden is an independ-
ent prognostic indicator for recurrence (hazard ra-
tio [HR]: 1.78; p = 0.005).5 
In years to follow, studies comparing systemic 
adjuvant treatment of CM to those receiving place-
bo after surgical treatment have shown improved 
regional relapse free survival (RFS) and OS in pa-
tients with targeted therapy.7-9 That knowledge 
combined with results of MSLT-II and DeCOG led 
clinicians to belief, that CLND in patients with pos-
itive SLN is no longer warranted.10 
But group of stage III patients is one of the 
most heterogeneous groups with expected 5-year 
OS ranging from 30–60% and adjuvant systemic 
therapy is potentially toxic and costly.11,12 In case of 
first reported adjuvant systemic therapy trial, 43% 
of patients receiving ipilimumab had grade 3 or 4 
side effects but in later studies, the percentage has 
dropped to approximately 14%.7,8 Toxicity rates 
have dropped and at the same time 1-year RFS has 
increased to 70.5% in completely resected stage III 
CM patients treated with anti-PD-1 agent nivolum-
ab and 75.4% in case of adjuvant pembrolizumab.13 
But one has to keep in mind that individual costs of 
adjuvant immunotherapy treatment in our coun-
try can reach up to 67.000 Euros per year. How to 
make adjuvant systemic treatment combined with 
suitable follow up of regional lymph node basin 
available to all patients are nowadays concerns of 
many clinicians. 
Perhaps additional piece of information is hid-
ing in the SLN burden. Studies in the past have as-
sociated SLN burden of > 1 mm with significantly 
worse outcome and a need for adjuvant systemic 
treatment. On the other hand different studies 
were not able to confirm the minimal SLN burden 
as reproducible factor for excellent survival at all 
sites. Despite that it seems, that burden of < 0.1 mm 
is associated with 5-year survival of 83–91%, with 
non-SLN positivity rates between 0 and 12%.14 
The aim of our study was to compare survival 
based on retrospective analyse of stage III CM 
from national CM base to current understanding 
of lymph node surgery. 
Patients and methods
Data of CM patients treated at the Institute of 
Oncology Ljubljana (OI) were prospectively col-
lected into clinical melanoma registry. Data of SLN 
biopsy procedures were collected since January 
2000, the year of the SLN biopsy introduction in 
Slovenia. Complete lymph node dissection data 
were registered since 2003. In Slovenia all CM sur-
gical procedures (with exclusion of skin biopsy) 
are performed at the OI. Clinical melanoma regis-
try of the OI serves as a substitute of the national 
CM database.
Data of 2426 patients with CM (CM ≥ TIb based 
on confirmed histology) undergoing SLN biopsy at 
the OI between 2000 and 2015 were analysed. The 
SLN biopsy procedure was performed according to 
established recommendations.15 During described 
period, gross and microscopic examination of SLN 
was performed by 4 dedicated pathologists at the 
institute using SLN protocol that has been adopted 
by the EORTC as the standard procedure for path-
ological handling of SLN for CM.16 The false nega-
tive rate (FNR) was defined as false negative/true 
positive combined with false negative. All patients 
with positive SLN and performance status ECOG 
0–2, who agreed to further surgical treatment, un-
derwent CLND. Altogether there were 455 patients 
with positive SLN and CLND.
To that number we added the analysis of 149 pa-
tients with synchronous primary CM and clinically 
detected regional lymph node metastasis (SLNM), 
121 patients with metachronous primary CM and 
regional lymph node metastasis (MLNM), and 64 
patients with melanoma of unknown primary site 
(UPM). Synchronous metastases were defined as 
metastases detected clinically prior to surgery or 
occurring within 6 months of the initial CM diag-
nosis. Patients with first recurrence of the disease 
in the regional lymph node basin later in course of 
the disease were classified to the MLNM group. 
UPM was defined as clinically detected and his-
tologically confirmed nodal melanoma metastases 
with no evidence of primary lesion. Patients with 
synchronous nodal and in-transit metastases were 
excluded from the study as were patients with 
previously excised pigmented skin lesion without 
proper histological evaluation. Finally, data of 789 
patients after complete lymph node dissection di-
vided in four groups (CLND, SLNM, MLNM and 
UPM) operated between 2003 and 2015 were retro-
spectively analysed.
The date of study closure was January 15th 
2019. Data were summarized as mean ± SD, un-
less otherwise specified. Chi-square test was used 
for categorical variables while quantitative vari-
ables were compared using Kruskal-Wallis test. 
Overall survival (OS) time was calculated from the 
date of the excision of primary lesion (or the date 
of lymph node dissection in the case of UPM) to 
the date of death and censored at the closing date 
for survivors. Survival analyses were performed 
Radiol Oncol 2021; 55(1): 50-56.
Peric B et al. / Resected stage III melanoma controversy52
by constructing Kaplan-Meier survival curves 
and compared using log-rank tests. Comparisons 
between groups of patients undergoing complete 
lymph node dissection (CLND, MLNM, SLNM 
and UPM) for each parameter were calculated us-
ing χ2 or nonparametric Kruskal-Wallis analysis as 
indicated. Statistical analysis was performed using 
SPSS for Windows, version 22.0. A p-value < 0.05 
was considered statistically significant. 
Ethical considerations
The study was approved by the Institutional 
Review Board Committee and was conducted in 
accordance with the ethical standards laid down in 
an appropriate version of the 1964 Declaration of 
Helsinki.
TABLE 1. Demographics of sentinel lymph node biopsy (SLNB) group
Negative 
SLN
No. (%)
Positive SLN
No. (%)
Unfound SLN
No. (%)
All SLNB
No. (%)
Number of 
patients 1837(75.7) 519 (21.4) 70 (2.9) 2426 (100.0)
Tumour site
   Head 174 (9.5) 34 (6.6) 21 (30.0) 229 (9.4)
   Neck 30 (1.6) 6 (1.2) 7 (10.0) 43 (1.8)
   Trunk 857 (46.7) 268 (51.6) 30 (42.9) 1155 (47.6)
   Limbs 776 (42.2) 211 (40.7) 12 (17.1) 999 (41.2)
Breslow thickness (mm)
   < 1.5 757 (41.2) 67 (12.7) 24 (32.9) 848 (34.8)
   1.5–3.5 735 (40.0) 226 (43.5) 26 (37.1) 987 (40.7)
   3.5 323 (17.6) 224 (43.2) 20 (28.6) 567 (23.4)
   Unknown 20 (1.1) 3 (0.6) 1 (1.4) 24 (1.0)
Ulceration
   Yes 554 (30.2) 234 (45.1) 40 (57.1) 828 (34.1)
   No 1054 (57.4) 232 (44.7) 22 (31.4) 1308 (53.9)
   Unknown 229 (12.5) 53 (10.2) 8 (11.4) 290 (12.0)
Tumour subtype
   SSM 260 (14.2) 62 (11.9) 9 (12.9) 331 (13.6)
   NM 277 (15.1) 129 (24.9) 10 (14.3) 416 (17.1)
   LMM 14 (0.8) 1 (0.2) 1 (1.4) 16 (0.7)
   ALM 29 (1.6) 10 (1.9) 0 (0.0) 39 (1.6)
   Other 105 (5.7) 25 (4.8) 2 (2.9) 132 (5.4)
   Unknown 1152 (62.7) 292 (56.3) 48 (68.6) 1492 (61.5)
ALM = acral lentiginous melanoma; LMM = lentigo malignant melanoma; NM = nodular 
melanoma; SLN = sentinel lymph node; SLNB = sentinel lymph node biopsy; SSM = superficial 
spreading melanoma 
Results
Between 2000 and 2015, 2426 CM patients had SLN 
biopsy procedures at the OI. Positive SLN was 
found in 519 (21.4%) patients, of these 13 (2.5%) 
had metastatic lymph nodes in two nodal basins. 
The size of SLN metastasis was recorded (in mm) 
in 91.7% of cases. 
SLN biopsy procedure was unsuccessfully per-
formed in 70 patients (70/2426, 2.9%). Preoperative 
lymphoscintigraphy failed to detect the SLN in 
23/2426 (0.9%) patients. Unsuccessful surgical re-
trieval was recorded in 47/2426 (1.9%) patients. 
Lymph node basin with the highest percentage of 
unsuccessful surgery was neck 24/310 (7.7%), fol-
lowed by interval lymph nodes 6/115 (5.2%), axilla 
13/1238 (1.1%) and groin 4/693 (0.6%). 
In 455 patients with positive SLN, CLND was 
performed. Patients with unsuccessfully retrieved 
SLN or negative SLN and lymph node recurrence 
discovered during follow up (88/1837; 4.7%) were 
considered as false negative (FN). According to 
that the FNR was 14.5%. In addition, there were 
33 patients with only wide local excision who de-
veloped nodal recurrence. Since there was no sta-
tistically significant difference in OS between the 
two subgroups of patients (p = 0.373) they were 
in further analysis merged together as MLNM. 
Demographics of patients undergoing SLN biopsy 
are depicted in Table 1.
Demographics of four groups of patients un-
dergoing complete lymph node dissection (CLND, 
SLNM, MLNM, UPM) are summarized in Table 2.
Median follow-up of patients after lymphad-
enectomy was 47 months (range 20 days - 198 
months). At the time of data cut-off, 60.1% of pa-
tients died. The 5-year OS of CLND group was 
58%, MLNM 47%, SLNM 21% and UPM 45%, 
while 10-year OS was as follows: 45% for CLND, 
29% for MLNM, 19% for SLNM and 40% for UPM 
group (Figure 1). 
The 5-year OS of MLNM group was significant-
ly worse than survival of CLND group (47% vs. 
58%; p = 0.003). However, the 5-year OS of CLND 
group was heterogeneous based on different tu-
mour burden in SLN: < 0.3 mm 86%, 0.3–0.69 mm 
72%, 0.7–1.0 mm 61% and > 1.0 mm 49% (Figure 2). 
Patients with SLN tumour burden < 0.3 mm had 
the 5-year OS similar to SLN negative group (86% 
vs. 85%; p = 0.926). The 5-year OS of patients with 
SLN tumour burden > 1.0 mm was comparable to 
the MLNM group (49% vs. 47%; p = 0.280). 
The percentage of positive non-SLN differed 
according to the size of the SLN tumour burden; 
Radiol Oncol 2021; 55(1): 50-56.
Peric B et al. / Resected stage III melanoma controversy 53
3.2% (2/63) of patients with SLN metastasis < 0.3 
mm, 7.4% (5/68) of patients with SLN metastasis 
0.3–0.69 mm, 11.9% (7/59) of patients with SLN 
metastasis 0.7–1.0 mm, 23.0% (51/222) of patients 
with SLN metastasis > 1 mm and 32.6% (14/43) of 
patients with SLN metastasis of unknown size had 
positive non-SLN. 
Discussion 
Data of 2426 patients with CM undergoing SLN 
biopsy and 789 patients after CLND treated at the 
Institute of Oncology Ljubljana during 15-year 
period were retrospectively analysed. The results 
have shown that 5-year OS of patients with SLN 
tumour burden < 0.3 mm is comparable to OS of 
patients with negative SLN (p = 0.926). On the 
other end of spectrum were patients with SLN 
tumour burden of > 1 mm with survival com-
parable to patients with metachronous regional 
lymph node metastasis (5-year OS 49% vs. 47%, 
p = 0.280). Patients with CLND after positive SLN 
had significantly improved survival compared to 
those with dissection after delayed dissection (p 
= 0.003).
In last two decades three prospective rand-
omized studies have addressed the management 
of regional lymph nodes in CM patients.2,5,6 The 
result of the first, MSLT-I, confirmed the critical 
role of the SLN biopsy although it did not demon-
strate the melanoma specific survival (MSS) ben-
efit. Despite that, the results did show that early 
removal of lymph node metastases in intermediate 
thickness CM could improve survival. 10-year dis-
tant disease free survival was 54.8% in the group 
with intermediate thickness CM following CLND 
after positive SLN biopsy and 35.6% in the case of 
observation and nodal recurrence. According to 
our analysis 10-year OS was 45% in CLND group 
compared to the 29% OS of the MLNM group 
which had the characteristics similar to the true 
observational group. The survival difference was 
slightly smaller in our population in comparison 
to MSLT-1 trial which can be explained by popula-
tion differences. MSLT-I included 81.6% of patients 
with intermediate thickness CM with median 
thickness of 1.8 mm in biopsy group, while median 
thickness in our population was 3 mm. One third 
of patients had SLN tumour burden > 1 mm.2,11 
In our population the percentage was 48.8%. The 
observed differences in survival indicate that the 
benefit of the CLND is not limited only to patients 
with intermediate thickness CM.
TABLE 2. Demographics of the four groups with lymph node dissection 
CLND
No. (%)
MLNM
No. (%)
SLNM
No. (%)
UPM
No. (%) p
Number of 
patients 455 (57.7) 121 (15.3) 149 (18.9) 64 (8.1)
Age (years) 0.005
   Mean 56 60 59 58
   Median 56 64 61 61
Gender 0.198
   F 206 (45.3) 63 (52.1) 65 (43.6) 23 (36.0)
   M 249 (54.7) 58 (47.9) 84 (56.4) 41 (64.0)
Primary tumour site 0.254
   Head 29 (6.4) 16 (13.2) 25 (16.8) -
   Neck 5 (1.1) 4 (3.3) 2 (1.3) -
   Trunk 235 (51.6) 48 (39.7) 64 (43.0) -
   Limbs 186 (40.9) 53 (43.8) 58 (39.0) -
Breslow thickness (mm) < 0.001
   Mean ± SD 3.9 ± 0.1 3.5 ± 0.3 8.5 ± 0.8 -
   Median 3.0 2.6 6.0 -
   < 1.5 60 (13.2) 28 (23.1) 12 (8.1) -
   1.5–3.5 202 (44.4) 54 (44.6) 21 (14.1) -
   > 3.5 190 (41.8) 35 (28.9) 105 (70.5) -
   Unknown 3 (0.7) 4 (3.3) 11 (7.4) -
Clark level < 0.001
   II 2 (0.4) 1 (0.8) 1 (0.7) -
   III 87 (19.1) 32 (26.4) 16 (10.7) -
   IV 234 (51.4) 50 (41.3) 63 (42.3) -
   V 41 (9.0) 7 (5.8) 33 (22.1) -
   Unknown 91 (20.0) 31 (25.6) 36 (24.2) -
Ulceration
   Present 197 (43.4) 47 (38.8) 91 (61.1) - < 0.001
   Absent 213 (46.8) 52 (43.0) 18 (12.1) -
   Unknown 45 (9.9) 22 (18.2) 40 (26.8) -
Number of positive nodes < 0.001
   Mean ± S.D. 1.6 ± 1.8 3.3 ± 4.0 4.3 ± 5.4 4.5 ± 7.0
   Median 1 2 2 2
Diameter of the largest lymph node metastases (mm) < 0.001
   Mean ± S.D. 3.5 ± 5.7 35.3 ± 30.7 20.8 ± 14.2  46.0 ± 27.2
   Median 1.4 28 16 47
CLND = completion lymph nodes dissection; MLNM = metachronous lymph node metastasis; SLNM 
= synchronous lymph node metastasis; UPM = unknown primary site metastases
Radiol Oncol 2021; 55(1): 50-56.
Peric B et al. / Resected stage III melanoma controversy54
Studies following MSLT-I and addressing the 
question of improved OS survival after the CLND 
included small proportion of patients with SLN 
tumour burden > 1 mm (two thirds of patients in 
each DeCOG study arm had SLN tumour burden 
≤ 1 mm) which would, together with exclusion of 
patients with head and neck CM and those with 
extracapsular extension, indicate selection bias 
during study accrual.5,6,11 One interesting notion 
comparing our results to the results of the MSLT-
II is, that they have include approximately 6% less 
patients with ulceration (37.0% of CLND com-
pared to our 43.3%) and 20% less patients with 
thick melanoma (21.8% MSLT-II vs. 41.8%). The 
percentage of patients with SLN tumour burden 
> 1 mm was 21.7% in MSLT-II CLND group and 
48.8% in our study respectively. The comparison 
imposes a question whether one can rely on the 
prospective randomized trials while facing a spe-
cific real life population? Differences in our na-
tional results indicate that direct implementation 
of the conclusions of randomised trials may not 
always be suitable. Results of DeCOG and MSLT-
II studies failed to prove the OS survival benefit 
of the CLND. In case of our cohort the 5-year OS 
of patients following CLND was improved by 
11% compared to the MLNM group (58% vs. 47%, 
p = 0.003) with no signifficant difference in the 
Breslow thicknes or presence of ulceration be-
tween the two groups.
Intriguing relationship between Breslow thick-
ness and nodal burden was observed. In our study 
the worst OS survival was associated with SLNM 
group with only 21% alive after 5 years. The group 
of SLNM patients had substantially thicker CM 
yet their nodal burden was smaller compared to 
MLNM group (35.3 ± 30.7 mm MLNM vs. 20.8 ± 
14.2 mm) indicating different primary tumour bi-
ology but also indicating the effect of the delayed 
lymphadenectomy on the size of the nodal burden. 
If the timing of lymphadenectomy is a vital part 
of treatment the concern about possible loss of re-
gional control during observation after SLN biopsy 
is raised. Many clinicians are aware that unresect-
able regional disease is a serious clinical problem 
in CM. At the moment it is not known in how many 
cases observation and sequential regional relapse 
would actually cause loss of regional control.11 
But not only regional control, other results could 
also be influenced by timing, as indicated in the 
Delgado meta-analysis. They concluded that there 
appears to be a time-dependent disease specific 
survival advantage related to early or immediate 
surgery regardless of the extent of the procedure 
compared to delayed or none in the case of nodal 
metastases.17 
Can we reassure our patient that it is safe to 
leave the possible CM metastases in lymph node 
basin in cases where SLN biopsy is not followed 
by CLND? Many would argue that in the case of 
high risk for disease progression, small tumour 
burden in lymph node basin makes no change.6,11 
Interestingly that is in contrast to some basic re-
search showing that especially in CM models stem-
like tumour cells have been found to reside in the 
vessels in the vicinity of lymphatic nodes, suggest-
FIGURE 1. Overall survival (OS) of groups with completion 
lymph nodes dissection (CLND), synchronous lymph node 
metastasis (SLNM), metachronous lymph node metastasis 
(MLNM), unknown primary site metastases (UPM).
FIGURE 2. Overall survival (OS) according to sentinel lymph 
node (SLN) tumour burden.
Radiol Oncol 2021; 55(1): 50-56.
Peric B et al. / Resected stage III melanoma controversy 55
ing that there is a kind of ‘lymphovascular’ stem 
cell niche which is not removed without CLND. 
It is speculated that these stem-like tumour cells 
might ‘hibernate’ for a long time span within the 
lymphovascular niche, and may form new tumours 
even years after surgical removal of the primary 
tumour. Similarly, the persistence of metastatic tu-
mour cells in non-SLN subcapsular sinuses might 
also relate to a tumour cell survival supporting 
function of lymphatic vessels, which could play a 
role in premetastatic lymphatic niches as well.18 On 
the other hand, lymphatic endothelial cells (LEC) 
are expressing PD-L1 surface receptors that direct-
ly interface with leukocytes and causes dysfunc-
tional T cell activation, so one would speculate that 
the risk of tumour progression can be minimized 
with adjuvant immunotherapy. Studies aimed at 
adjuvant therapy in CM patients did show less re-
lapses compared to placebo group and indicated 
that adjuvant systemic therapy can lead to sus-
tained and durable survival benefit. However ad-
ditional validation of this approach with extended 
follow-up in patients receiving adjuvant systemic 
therapy for CM is warranted, including correla-
tion with OS data.19 It is important to note that tri-
als that influenced our understanding of stage III 
melanoma treatment (MSLT-1, MSLT-2, DeCOG) 
included patients with completely resected CM 
and SLN burden > 1 mm.11 
With results of MSLT-II and underpowered 
DeCOG trial indicating no benefit from CLND after 
positive SLN we can expect, that only a small num-
ber of patients will be advised to have CLND in 
the future. It will be up to clinicians to decide, who 
with stage III disease should receive adjuvant sys-
temic therapy and the decision will be based only 
on information gathered from SLN biopsy instead 
on information gathered from CLND available for 
adjuvant trials. Unfortunately, until new conclu-
sions are available, results from previous adjuvant 
trials cannot simply be extrapolated to patients 
who only had SLN biopsy. The information about 
the non-SLN status might be lacking.20 Our own 
results show that 17.4% of patients (79/455) had 
positive non-SLN and with that possible decision 
influencing information.
The issue of additional information gained from 
CLND was addressed by Verver and colleagues. 
They used a retrospective cohort of SN-positive 
patients previously collected and described to con-
struct a model of risk stratification based solely on 
primary CM and SLN biopsy information. Their 
model is based on presence or absence of the ul-
ceration and SLN burden of > 1 mm or ≤ 1 mm. 
They concluded that CLND upstaged 19% of pa-
tients in the N-category and 5% of patients in AJCC 
stage 8Th edition (6% AJCC stage upstaging in the 
7th edition). The survival analysis showed signifi-
cant difference between low risk group (absent ul-
ceration and SLN burden ≤ 1 mm) with 5-year MSS 
of 82.4% and intermediate risk (ulceration present 
and SLN ≤ 1 mm or ulceration absent and SLN > 1 
mm) with survival around 67.6% and substantial 
gap between intermediate and high risk group (ul-
ceration present and SLN > 1 mm) with 44% 5-year 
MSS in the later.20 Verver’s model is a significant 
step to understanding the stage III survival het-
erogeneity but if tumor burden is an important 
prognostic indicator, four group prognostication 
sounds somehow crude. In our analysis we defined 
groups according to SLN burden. The OS survival 
analysis done according to the four group strati-
fication caused previously described CLND curve 
to fan out. The analysis proved that group of pa-
tients with SLN burden > 1 mm are high risk pa-
tients with 5-year OS of 49%. In fact, their survival 
did not differ statistically from the MLNM group. 
On the other side of the spectrum are patients with 
SLN burden < 0.3 mm with excellent prognosis and 
5-year OS of 86% similar to the group with nega-
tive SLN. In the middle are those with SLN bur-
den > 0.3 mm and ≤ 1 mm with 60–70% 5-year OS. 
Additional analysis showed that 9.4% of these pa-
tients had metastases in non-SLN. Based on current 
recommendations those patients would not receive 
any additional adjuvant treatment. For those CM 
patents not receiving adjuvant systemic treatment 
and not being able to undergo regular nodal ba-
sin US, surgery remains a treatment option, which 
should be taken under consideration.
Conclusions
Stage III melanoma patients are extremely hetero-
geneous group with significant survival differenc-
es. Since not all of them can be treated with systemic 
adjuvant therapy, CLND after positive SLNB may 
be offered to selected CM patients. Considering 
adjuvant treatment, CLND provides independent 
prognostic information that at the moment cannot 
be replaced satisfactorily by other variables. 
Authors‘ contribution
BP contributed to the conception of the study, 
drafted the work and interpretated the data. SM 
Radiol Oncol 2021; 55(1): 50-56.
Peric B et al. / Resected stage III melanoma controversy56
performed data acquisition, analysis and contrib-
uted to data interpretation. AP contributed to in-
terpretation of data and substantively revised the 
manuscript. MH made substantial contributions to 
the conception and design of the work and added 
critical remarks to the revised version. JZ contrib-
uted to the conception, interpretation of data and 
substantively revised the manuscript.
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