Added value of OCT for diagnosing recurrent BCC after non-invasive treatment

Skin cancer incidence rises worldwide due to high sun exposure and ageing.
Basal cell carcinoma (BCC) is the most prevalent form, with a lifetime risk of
16-20% in the Netherlands.[1] Although there are many histological subtypes, a
simplified classification by Rippey [2] roughly groups all BCCs into three
histopathological subtypes: superficial, nodular and infiltrative. Knowledge of
the histopathological subtype is especially relevant in determining the optimal
treatment.
A third of all BCCs are of the superficial subtype and are nowadays often
treated with topical therapy (e.g. imiquimod, 5-fluorouracil, photodynamic
therapy) to optimize cosmetic outcome and limit invasive and scarring
procedures. These treatments generally have higher recurrence rates opposed to
surgical excision, making adequate follow-up a necessity. As a consequence, the
development of improved non-invasive diagnostic methods becomes increasingly
relevant in the follow-up of these patients.
Currently, the histopathological examination of a punch biopsy remains the gold
diagnostic standard to confirm BCC diagnosis and subtype [3], however a punch
biopsy is an invasive procedure that may be painful and carries a (small) risk
of complications such as bleeding, scarring and infection. With the high volume
of BCCs and potential drawbacks of invasive diagnostics, interest in
non-invasive diagnostic methods is increasing. Optical coherence tomography
(OCT) is an imaging technique that generates real-time in vivo cross-sectional
images of tissue microarchitecture with a depth of 1.5-2 mm.[4], OCT is based
on light interferometry: the interference of two optical beams reflected by the
tissue produces distinguishable shades in the black and white spectrum.
Morphologic characteristics of BCC that may be distinguished on OCT images have
been established in recent years.[5]
The diagnostic accuracy of OCT has been investigated in a number of studies,
using conventional OCT with relatively large sample sizes, demonstrating quite
large ranges in sensitivity (58-95.7%) and specificity (43-96%).[6-8] In a
recent prospective cohort study conducted at our department, we found a
specificity of 76.8% with a sensitivity of 95.2% in the diagnosis of BCC. The
AUC for clinical examination increased from 85.6% to 91.2% when OCT was added
(p=0.061).[9]
In this study, specificity to detect superficial BCC significantly increased
from 47.8% with clinical and dermoscopic examination alone to 78.3% when OCT
was added.
Therefore we hypothesize that the adjunct use of OCT might increase the
detection of recurrent BCC over clinical and dermoscopic examination alone in
patients with a superficial BCC which were treated with topical therapy, and
possibly at an earlier stage. .Hussain et al., evaluated whether the addition
of OCT to clinical and dermoscopic examination increased detection rate of
recurrent BCC in patients who underwent curettage and/or MAL-PDT. With the
adjunct use of OCT, the detection rate increased by 50% (6/12). In 7% of the
cases, OCT unrightfully raised suspicion for BCC recurrence (3/43), leading to
a PPV of 80%. *
We hypothesize that the addition of OCT to clinical and dermoscopic examination
increases detection rate of recurrent BCC in patients with a superficial BCC
which were treated with topical therapy. Increased detection and consequently
detection at an earlier stage enables early re-treatment and herewith might
reduce the burden of the BCC. Detection of BCC subtype by means of OCT is
relevant, since recurrent superficial BCC may be treated with another round of
imiquimod, whereas as nodular and infiltrative BCCs will be excised.

To investigate the added value of OCT as a non-invasive tool for the diagnosis
of recurrent BCC.

In this prospective cohort study, patients who underwent non-invasive therapy
for a histopathologically confirmed superficial BCC will be included. Patients
will receive patiënt information via e-mail or postal mail, prior to their
visit at the clinic. This will give the patient sufficient time to consider
participation.
Clinical and dermoscopic examination will be conducted by the treating
physician and confidence in presence of recurrent BCC will be scored using a
five-point Likert-scale (4= certain recurrent BCC and certain about the
subtype, 3= certain recurrent BCC, but doubtful about the subtype, 2=not sure,
1=probably no recurrent BCC, 0=surely no recurrent BCC).
Prior to inclusion, all eligible patients will be provided with written
information about the study, at their first presentation at the outpatient
clinic. The coordinating investigator, who will be present at the outpatient
clinic, will thereupon call the patient and further explain the study. This
creates an opportunity for the patient to ask further questions regarding the
study to the investigator. If the patient is willing to participate, the
informed consent form is signed by the patient and the investigator. After
informed consent is obtained, OCT images will be obtained of the treated skin
area and confidence in presence of recurrent BCC will be scored for OCT using
the same five-point Likert-scale as mentioned above. In case of a Likert score
of 3 or 4 based on clinical and dermoscopic examination, a punch biopsy will be
obtained to confirm recurrent BCC, according to regular care. In case of a
Likert score of 0 or 1 based on clinical and dermoscopic examination and high
confidence (Likert score 3 or 4) based on OCT, a punch biopsy will also be
obtained to confirm the presence of recurrent BCC. In the latter case, the
diagnostic strategy is based on OCT and not conform regular care. In clinical
practice, no biopsy is performed in cases with no or only low suspicion of
recurrent BCC based on clinical, dermoscopic and OCT examination. However, for
the purpose of the study, these patients will be offered the choice to obtain a
punch biopsy in order to histopathologically confirm that there is indeed no
residual or recurrent BCC present. The sample of patients who agree to obtain a
biopsy will be used to estimate the frequency of histopathologically verified
recurrent BCC in patients with negative results on clinical/ dermoscopic
examination and OCT examination, respectively.

Optical Coherence Tomography

Imaging with the OCT device is a non-invasive and harmless technique, yet
capable of collecting valuable information for the clinician and more
importantly the patient. There are no estimated risks of this technique. A
punch biopsy for therapeutic indications is common practice at the dermatology
department. Injection of lidocain 1% as local anaesthetic could induce a short
burning sensation of the skin. After local anaesthesia, the biopsy is painless.
Independent of the patient*s decision to be part of the study or not, there are
certain risks associated with the biopsy, such as scar formation, bleeding,
wound infection and nerve damage. These risks are not influenced by OCT
imaging. Only if there is low confidence in the presence of recurrent BCC based
on clinical and dermoscopic examination and high confidence in the presence of
recurrent BCC based on OCT (certainty about BCC diagnosis (and possibly
subtype)) a punch biopsy will be performed, which is based on OCT findings.
In clinical practice, no biopsy is performed in cases with no or only low
suspicion of recurrent BCC based on clinical, dermoscopic and OCT examination.
However, for the purpose of the study, these patients will be offered the
choice to obtain a punch biopsy in order to histopathologically confirm that
there is indeed no residual or recurrent BCC present. The sample of patients
who agree to obtain a biopsy will be used to estimate the frequency of
histopathologically verified recurrent BCC in patients with negative results on
clinical/ dermoscopic examination and OCT examination, respectively.