Reviewer’s report
Title: 
The potential risk of contralateral non-sentinel groin node metastasis in
women with early primary vulvar cancer following unilateral sentinel node
metastasis: a single center evaluation in University Hospital of Düsseldorf
Version: 
0 
Date: 
02 Nov 2020
Reviewer's report:
This work from Winarno et al addresses a topic of great clinical interest because
growing incidence of vulvar cancer. Lymph node metastasis have been shown to
represent the most significant prognostic factor in vulvar carcinoma and sentinel
lymph node biopsy (SLNB) has been proposed as a minimally invasive surgical
approach for lymph node staging but effective at reducing the morbidities related
to bilateral inguinal-femural lymphadenectomy. After the Groningen
International Study on Sentinel node in Vulvar Cancer (GROINSS-V-I) SLNB
showed to be safe in early-stage vulvar cancer. Interesting is to understand how
this procedure impacts the oncological outcomes, especially on contralateral
groin's node metastasis after IFL. Nowadays, bilateral IFL is suggested after a
finding of positive lymph node sentinel but this recommendation is debatable in
case of bilateral SLN biopsy and only unilateral positive sentinel node.
I sincerely appreciate this work, and I only have few comments I appointed
below. 
Sentinel lymph node biopsy is a surgical management topic and a wide
epidemiological, histological pattern dissertation appeared too verbose. The
background section should avoid the wide general introduction and focus on the
topic of the work reporting evidence-base on clinical and cost-efficency benefit
of SNLB. Improvement of quality life and reduction in morbility/mortality rates
are just mentioned at lines 74-75. I suggest to develop this aspect in order to
underline actuality of the debate.
As reported in 
Methods section free margin after resection was 3 mm but it could
be interesting understand if this cut-off was used as an inclusion criteria and if
data from free margin <3 mm have been analyzed. 
According to a large work of
Covens et al groin recurrence rates appeared to be similar between LND and
SLND only under optimal conditions (unifocal tumors < 4 cm, clinically non-
suspicious nodes in the groin, specific infrastructure, human resource,
appropriate techniques, and procedures) but methods' section lacks of clear
inclusion and exclusion criteria. Nevertheless, an ongoing nationwide study in
Sweden is investigating the possibility of extending the inclusion criteria and
could change the clinical approach to SLNB (ClinicalTrials.gov ID:
NCT04147780). 
The work took place in a German Hospital and German guidelines stress the
importance of a well conducted counseling concerning advantages and possible
oncological risks of this technique. This aspect is not mentioned by the authors
and I suggest to introduce this concept in the Discussion. At the same way is
useful to underline as every case of VC and SNLB benefits of a centralized
management in a high-volume center with an experienced team in marking
sentinel lymph nodes. 
The authors followed a SNLB protocol from GROINSS-V trial and not others or
more recent protocols are mentioned in the discussion. Latest evidence in
literature indicate that sentinel lymph node detection is facilitated by a
combination of radioactive tracer and blue dye or indocyanine green in order to
reduce the false negative results. From a perspective of a critical analysis of
current and future scenarios I suggest to consider the manuscript of 
Collarino et
al. (DOI: 10.1007/s00259-019-04650-8).
In the Discussion the authors correctly reported the most know prognostic
factors. Nonetheless they did not consider the perineural invasion though it has
been shown an important independent prognostic factor of unfavorable course. I
suggest to annoverate this aspect among limits of the study citing this manuscript
as reference: DOI: 10.1016/j.ejso.2019.07.029.
Vulvar cancer in pregnancy is a real concern and management is a clinical
challenge for the gynecologist. Despite the interesting case reported in the
manuscript, in my opinion, VC in this particular setting is worthy of a proper
work. Timing of diagnostic procedure, use of radioactive traces and treatment
have to be deeply analyzed and a systematic review of the literature is suggested
as further future paper.
I will be very happy to review the revised version of this work.
Best regards
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