Treatment of basal cell carcinoma using a one-stop-shop with reflectance confocal microscopy: a randomized controlled multicenter trial

Basal cell carcinoma (BCC) is the most prevalent skin cancer, and its
prevalence is increasing. Histological analysis of punch biopsy remains the
golden standard to confirm the clinical diagnosis of BCCs and dividing
subtypes. However, due to the rising incidence of BCC there is a need for more
efficient, non-invasive methods to diagnose BCCs. The use of real-time in vivo
reflectance confocal microscopy (RCM) to diagnose BCCs has proven successful to
address this need. Various studies have demonstrated that RCM is safe and
accurate (sensitivity and specificity) to diagnose BCCs. Reported sensitivity
and specificity for RCM in diagnosing BCC range from 83.9%-91.6% and 95.7%-97%,
respectively. Furthermore, Peppelman et al. and Longo et al. recently reported
on RCM features that might classify between nodular, micronodular, superficial
and infiltrative subtypes of BCC. Incorporating RCM as non-invasive diagnostic
tool in a BCC one-stop-shop (OSS) concept for lesions suitable for conventional
surgical excision, in concordance with current Dutch guidelines, might reduce
time between clinical diagnosis and treatment, administrative workload and
costs. One-stop-shop implies that at the day of the initial outpatient clinic
consultation, the diagnosis and treatment both take place. Surgical treatment
of BCCs is generally performed under local anesthesia, which makes it suitable
for an OSS approach.

Primary: to compare the OSS concept with RCM in the surgical treatment of BCCs
with current standard of care.
Secondary: to assess the accuracy (sensitivity and specificity) of diagnosing
BCC by comparing RCM with punch biopsy as diagnostic tools.
Third: to assess the accuracy (sensitivity and specificity) of BCC subtyping by
comparing RCM diagnosis, including inter- and intra-observer agreement, with
final pathology report.
Fourth: to compare the following items of the OSS concept with RCM in the
surgical treatment of BCCs with current standard of care: 1. patient
satisfaction of the RCM OSS concept for the surgical treatment of BCCs. 2.
throughput time, defined by the time between arrival at consultation until end
of surgical treatment at our outpatient clinic.

Prospective non-inferiority, randomized controlled trial

I Study group: clinically suspected new primary BCC lesion will be diagnosed
and divided into subtypes using RCM imaging (Vivascope 1500; Lucid
Technologies, Henrietta, NY, USA) according to a standardized protocol. After
the diagnosis, excision of the BCC lesion with adequate margins will be
performed on the same day at the Department of Dermatology according to the
one-stop-shop concept. Clinically suspected primary BCCs that are not confirmed
by RCM will also receive surgical treatment with a margin of 3mm.

II Control group: clinically suspected new primary BCC lesion will be diagnosed
and divided into subtypes according to current standard of care. A conventional
3mm punch biopsy will be performed in the most elevated part of the lesion
using local anesthetics (1% xylocaine/adrenaline). Biopsy specimen will be
analyzed by a pathologist (within 2 weeks). After the diagnosis, excision of
the BCC lesion with adequate margins will be performed within the following 4
weeks according to current standard of care. Clinically suspected primary BCCs
that are not confirmed by punch biopsy will also receive surgical treatment
with a margin of 3mm.

Subjects participating in the study will be informed and will have to provide
written informed consent prior to enrollment. Study participation will not
result in additional follow-up visits other than clinically required 3 months
post-operative.
Real-time in vivo RCM uses a confocal microscope to noninvasively image a thin
surface of the skin at high resolution directly without the need for invasive
biopsies. The diagnostic procedure itself is painless and no side effects have
been reported. Outcome measures involve routinely processed surgical specimen
after excision, patient satisfaction, calculation of throughput time and
analyzing diagnostic accuracy of the RCM procedure in subtyping BCC lesions.
All together the burden due to the study is minimal. Possible inconvenience for
participating patients in the study group include that specific features for
BCC subtyping are still being established. Therefore a potential side effect
for those patients may include: less accurate subtyping of BCCs resulting in
less adequate surgical margins. At the same time, RCM imaging may be of
additional value in scanning the complete lesion, which potentially prevents
missing a more aggressive part of a tumor in contrast to a biopsy.
Thus there is a potential benefit for the participating subject, namely
non-invasive confirmation of clinical suspected BCC lesion followed by direct
surgical treatment. Considering the relatively quick and simple procedure,
non-invasiveness of diagnostic method, and the one-stop shop concept of
diagnosing and treating BCC at the same consultation, the balance between
burden, possible side effects and prospect for improvement might be very
favorable.