Comment
High Tumor Clearance Rates With OCT
This study yielded a clearance rate of 95.70% for all BCCs, 96.10% for facial BCCs, and 93.75% for nonfacial BCCs. This rate is higher than the clinical or histologic clearance rate (or both) of earlier studies on facial and nonfacial BCCs, which ranged from 25% to 95%.8-11 In this study, we were able to utilize OCT and histology to confirm clearance. Optical coherence tomography, which has been shown to have a high sensitivity ranging from 86% to 95.7%, is therefore optimally used in treatment monitoring.19,26,28 Optical coherence tomography has a broader specificity range of 75.3% to 98% and was not utilized for diagnostic purposes in this study. Combining OCT with a color wheel dermoscopic approach was helpful in confirming treatment efficacy of nonsurgical therapies and is significantly more accurate than clinical analysis alone (P<.01).19,26,28
We suspect that the higher clearance rates observed in our study were due to the OCT-guided treatment protocol. Optical coherence tomography was used for margination while providing a modality for tailored treatment through visualization of residual tumor on clinically and dermoscopically clear follow-ups, given that several studies found residual tumor at the lateral edge of the tumor margin on histopathologic analysis.5 Utilizing noninvasive imaging technology to delineate tumor margins before treatment can improve efficacy and limit unnecessary treatment to the surrounding normal skin (eFigure 2).29
eFigure 2. A 67-year-old woman with a clinically evident erythematous macule at the center of a hypopigmented scarred nasal tip, which was found to be a biopsy-proven recurrent nodular basal cell carcinoma (BCC) in a surgical scar from prior Mohs micrographic surgery. A, A clinical photograph 2 months after 3 laser treatments showed normal-appearing skin. B, Optical coherence tomography 2 months after 3 laser treatments demonstrated hyperechogenic tumorlike silhouettes consistent with residual BCC (yellow outline).
After grouping lesions by number of laser treatments, the clearance rate remained similar among facial BCCs with 3 or fewer treatments (59/61 [96.72%]), but there was a slightly decreased clearance rate for facial BCCs with more than 3 treatments (15/16 [93.75%]), which may be explained by the need for more laser treatments for larger BCCs (eTable 3). The relationship between facial BCC size and number of laser treatments was found to correlate positively (Pearson r=0.319). The largest lesion (24 mm) was successfully treated with 5 treatments (Figure). The number of nonfacial lesions was limited in this study and was not statistically significant.
A, A 45-year-old woman with a 24-mm biopsy-proven nodular basal cell carcinoma (BCC) on the forehead appearing as a large erythematous crusted plaque. B, After 5 pulsed dye laser and fractional laser treatments, there was evidence of hypopigmentation at 4-month follow-up, but
there was no clinical evidence of residual BCC.
Cosmetic Outcome
Adverse effects, including erythema, purpura, blistering, and crusting, were short-term and well tolerated. Few patients had subsequent hypopigmentation in the initial months after treatment, which we consider an optimal cosmetic outcome. For example, the patient shown in the Figure would have required extensive reconstruction of the defect using bilateral rotation flaps with incisions along the hairline, grafting, or second-intention healing with partial closure to avoid brow-lifting.30 Given the relatively young age of this patient (a 45-year-old woman) and therefore limited skin laxity, secondary intention or even attempting to match grafted tissue could have resulted in a less than optimal cosmetic outcome. None of the patients experienced clinical or dermoscopic evidence of scarring from the laser treatment.
A few lesions were found to have subclinical inflammation on OCT, which might have obscured residual tumor on the 1-month follow-up scan. This condition may be similar to how pre-MMS diagnostic biopsy scars mask skin cancer during surgery, making it necessary to obtain additional layers beyond the biopsy scar tissue. This scar tissue would otherwise obscure tumor on histology during MMS, similar to subclinical inflammation obscuring residual tumor on OCT.21-23,31 Invasive and noninvasive management of skin cancers will have different healing times and therefore different optimal times to confirm clearance by histology compared to noninvasive imaging. All of the lesions in which inflammation was obscured on OCT 1-month posttreatment remained cleared. However, 1 lesion was found to be clear at a 4-week clearance scan after only 2 nonablative laser treatments and was confirmed as scar tissue on histology. Scar tissue on histology might have obscured any residual tumor. The patient appeared clinically and dermoscopically to have a milia in the same location only 5 months later; however, on OCT and histology, the lesion was confirmed to be a BCC.
Treatment Intervals
Several other studies either used a set number of treatments or determined the number of treatments based on clinical clearance.3-8 When determining the best treatment interval, we considered the period for patients to be clinically and dermoscopically healed to be 1 month. Patients came for their final follow-up scan an additional month after the final treatment in case there was any obscuring inflammation on OCT at 1 month. Given that patients responded well to nonablative laser treatment once skin clinically healed and most patients required 3 treatments, the PI began recommending a total of 3 treatments performed 4 to 6 weeks apart in clinical practice, followed by a final clearance scan 2 months after the third treatment. A period of 2 months was considered ideal for the final clearance scan because no inflammation was seen at the 2-month follow-up in the group of patients who had inflammation at the 1-month follow-up on OCT in our study. Some patients had an extended treatment duration because of noncompliance with the 4- to 6-week follow-up regimen. Although this extension of treatment duration potentially skews the clearance rate, we still included these patients, given the retrospective design of this study.
Lesions That Did Not Clear
Four BCCs did not clear, 3 of which were facial BCCs. All 4 lesions demonstrated residual tumor on OCT. Of the 3 facial lesions that did not clear:
• One was the patient who had obscuring inflammation at the 1-month follow-up and only scar tissue on histologic confirmation.
• Another was a pigmented BCC on the right cheek of a patient with Fitzpatrick skin type IV. This patient received 3 treatments without a response clinically or on OCT. (Most patients who showed complete clearance also showed reduction in tumor size after the first laser treatment. Of note, there were other patients who had lighter skin types with pigmented BCCs and all of these patients had complete response to this treatment regimen; therefore, we do not think that a pigmented BCC is an exclusion to this therapy.)
• The third was a BCC on the nose of a nonadherent patient, which may have contributed to the lack of clearance. We defined nonadherent patients as those who did not follow-up within the appropriate periods and who therefore ran the risk for tumor growth in between treatments.
The nonfacial BCC that did not clear had histologic features of focal sclerosing BCC, a more aggressive subtype of basal cell skin cancer.
Tumor Recurrence
Only 4 of 89 BCCs (4.49%) recurred, with a 5.41% (4/74) recurrence rate among facial BCCs. All recurrences lacked clinical and dermoscopic evidence of BCC but were found on follow-up OCT scan and confirmed with RCM. All recurrences were found 1.5 to 3.9 years posttreatment.
Recurrent tumors following MMS required, on average, more laser treatments than primary tumors to achieve successful tumor clearance, which we attribute to scar tissue from prior therapy obscuring recurrence, resulting in delayed diagnosis, and to inflammation and fibrosis masking residual tumors (eFigure 1). An added benefit of laser treatment is that all 4 recurrent tumors demonstrated improved cosmetic appearance of the original MMS scar.
The benefit of using OCT scans to check for recurrences is that OCT can find residual skin cancers despite the area looking clinically clear, which is especially important during clinical evaluation of a healed postsurgical scar for recurrence because OCT imaging allows us to look as deep as 2 mm under the skin. Nonsurgical treatments also enable us to leave skin intact and avoid creating scar tissue, which makes it easier to detect and manage recurrence.
Limitations
There were several important limitations of this retrospective study:
• Patients were treated by 1 of 5 medically trained fellows. Although the fellows worked under the supervision of the PI, variation in their work from one to another might have led to different end points.
• All patients who appeared clinically clear were offered biopsy to confirm clearance on histology. Some patients agreed to biopsy, but many did not because they were pleased with the cosmetic outcome, which is similar to other studies exhibiting only clinical clearance rates without providing histologic clearance following nonsurgical therapy.6 We believe that imaging with OCT circumvents this problem and offers more accurate confirmation than clinical or dermoscopic correlation alone, or the combination of the 2 modalities.
• Lack of treatment standardization and short length of follow-up can result in underestimation of the recurrence rate. In particular, most patients were followed up with OCT in less than 6 months. These are unavoidable features in a retrospective study and we are currently addressing this problem in a new prospective study.
Extended Follow-up
Although this study is not a prospective design, it does provide recurrence data over extended follow-up for the nonablative laser management of BCCs (eTables 4 and 5). Studies have demonstrated that MMS has a 5-year cure rate as high as 99% for BCC.32 Given the limited follow-up period of prior nonablative laser management studies, recurrences might not have been fully evaluated. Our study had a 4.49% recurrence rate for all BCCs and a 5.41% recurrence rate for facial BCCs but was not detectable by clinical examination combined with dermoscopic findings alone. All recurrences required the utilization of OCT or RCM or a combination of these modalities to be diagnosed. In 1 patient with recurrence, we were able to see residual tumor on both OCT and RCM without any inflammation obscuring the scan, given that 3 years had passed. Although 2 months is an optimal follow-up time for OCT, we have not found an optimal follow-up time for RCM, which is another reason why OCT might be preferable to other imaging modalities, such as RCM and high-definition OCT, that have higher resolution but provide less depth on imaging. Although only 40 of 89 patients (4.49%) had follow-up ranging from 3 years to greater than 5 years, long-term follow-up to date has been limited in prior studies.
We believe the high clearance rates and limited recurrence are secondary to the utilization of noninvasive imaging, as the majority of these recurrences would not have been diagnosed based on clinical and/or dermoscopic information alone. Additionally, the 4 biopsy-proven post-MMS recurrence patients that were treated in this study also may not have been diagnosed this early without the use of additional noninvasive imaging. In our opinion, although laser management can be used without noninvasive imaging guidance—dermoscopy, OCT, and/or RCM—this technology is critical not only for early detection but also for proper management of patients.