(Cost-)effectiveness of optical coherence tomography versus regular punch biopsy in the diagnosis and subtyping of basal cell carcinoma: a multi-center randomized non-inferiority trial

Currently, the gold standard for diagnosing and subtyping basal cell carcinoma
(BCC) is a punch biopsy. Since this technique is invasive, new non-invasive
diagnostic methods have been developed, including optical coherence tomography
(OCT). In patients with clinical and dermoscopic suspicion of BCC, OCT makes it
possible to confirm and subtype BCC with high confidence, thereby obviating the
need for a punch biopsy in a substantial part of patients. Hence, BCC diagnosis
and treatment can be accomplished in one day. As a result, patients experience
less distress and costs can be saved. We hypothesize that the use of OCT is
non-inferior in terms of (cost-)effectiveness compared to regular care. We
expect that punch biopsy can be avoided in a substantial part of patients. By
discussing diagnosis and treatment with the patient directly, care can be
provided more efficiently, preventing treatment delay and saving extra hospital
visits.

Primary Objective: To investigate if use of OCT is (cost-)effective in the
diagnostic work-up of patients with clinically and dermoscopically suspected
basal cell carcinoma (BCC).

Secondary Objective(s):
To explore if OCT is a more patient friendly approach compared to regular care.
To evaluate diagnostic performance of OCT with respect to the ability to
discriminate between BCC and non-BCC and ability to discriminate between BCC
subtypes.

Multi-centre randomized controlled multi-centre non-inferiority trial.

OCT guided diagnosis.

This study is developed to evaluate the (cost-)effectiveness of OCT in
diagnosing and subtyping BCC. Patients will be randomized into two study arms:
the intervention arm, where patients receive an OCT scan and the regular care
arm, where patients are diagnosed and treated according to regular care. In the
intervention arm, treatment will be guided by OCT diagnosis only if the OCT
scan leads to high certainty about the presence of BCC and BCC subtype. In
patients where the OCT diagnosis reveals no BCC, or if there is any doubt about
the presence of a BCC, or in case the subtype is not certain, the protocol
states that a biopsy will still be taken. The treatment decision will be then
be based on the result of the punch biopsy. We expect that in only 40% of
patients randomized to the intervention arm a biopsy can be omitted. In all
patients where a biopsy can be omitted, treatment is discussed and started or
planned. After discussion of the treatment a *safety* punch biopsy will be
taken in all patients of the intervention arm to ensure that the treatment plan
can be revised if patient prognosis would be seriously compromised. The results
of the safety biopsy will be evaluated by a dermatologist specialized in skin
cancer diagnosis and treatmend (Nicole Kelleners Smeets; NKS), who is not
involved in the evaluation of the primary and secondary outcomes. On the basis
of the result of the punch biopsy and the intended treatment strategy, this
dermatologist will decide whether the chosen treatment would harm the patient
or not. The following possibilities exist:

There is a risk that in patients with an OCT scan highly suspected for BCC
(including subtype), the lesion is no BCC. NKS will determine whether the
intended treatment is appropriate. For example in case surgery is chosen, and
the appropriate treatment for this lesion is also surgery, no action will be
undertaken. However, if surgery is chosen for a lesion which is no skin cancer,
this would harm the patient and NKS will change the planned treatment according
to regular care for that diagnosis.
There is also a risk that the treatment decision is based on a high confidence
in OCT diagnosis but the BCC subtype is misclassified. For all subtypes of BCC
surgery is the gold standard.[2] Therefore, if surgery is chosen as treatment,
NKS will not interfere. Around 40% of the BCC*s is of a superficial subtype and
these are usually localised on the trunk or extremities. Although surgery is
also the gold standard treatment for superficial BCC*s, treatment with
non-invasive therapy is regular care because of the nicer cosmetic appearance
and relatively high long term cure rates of 80%. Patients diagnosed with a
superficial BCC on the OCT scan, who upon biopsy appear to have a
non-superficial BCC (solid or infiltrative BCC), requiring excision, run the
risk of being treated non-invasively. However, the risk for this group to be
undertreated is relatively low, since recent literature shows that imiquimod,
which is the first choice treatment of superficial BCC, has cure rates of 81.8%
at 3-year follow-up in nodular BCCs.[13] According to regular care all BCC*s
treated non-invasively will have a 3 month follow-up visit, to ensure that
treatment was effective.
In summary, we conclude that the risks for included patients who consent to
participate in this study are minimalized because:
1. Only a small percentage of the patients is treated with a method that does
not allow for histological control, namely the patients with high suspicion for
superficial BCC;
2. All patients will receive a *safety* biopsy that will prevent us from
starting a totally inappropriate treatment that would harm the patient;
3. In case of treatment of a nodular or infiltrative BCC with a non-invasive
treatment, this treatment might still be effective and if not, the 3 month
follow-of visit will enable us to retreat the patient with surgery.