Research Letter
The cost of non-melanoma skin cancer (NMSC) has risen disproportionately relative to other malignancies, necessitating research into cost-effective management options.1 Mohs micrographic surgery (MMS) remains the gold standard for treatment of NMSC due to superior cure rates and cosmetic favorability.2 However, patients most affected by NMSCs are often poor surgical candidates due to advanced age, frailty, comorbidities, and other risk factors.3 Furthermore, elderly patients with limited life expectancy may not experience the long-term benefits of MMS.4 Superficial x-ray therapy (SXRT) has been used to treat NMSCs for over a century, and despite its demonstrated efficacy and relatively minor long-term sequelae (i.e., radiotoxicity, telangiectasias, fibrosis, and hypopigmentation), SXRT remains an underutilized tool in dermatologists’ armamentariums.3 Recent literature has highlighted the reintroduction of SXRT due to more precise equipment, ease of use, and cost-effectiveness.3,4 Although SXRT treatment guidelines are reasonably cost-effective, hypofractionated scheduling, defined as greater fraction sizes (300–800 cGy) delivered in fewer (10 or less) total treatments and administered daily, on alternate days, or once weekly, may further reduce treatment-associated costs and provide comparable cure rates.5
To evaluate hypofractionated SXRT in the management of non-aggressive NMSCs, we conducted a single-institution 22-year retrospective analysis of 2490 biopsy-proven NMSCs (449 nodular BCC, 176 superficial BCC, 66 invasive SCC, 1759 SCC in situ, and 40 combined) from 1082 elderly patients treated between January 1, 2000, and June 1, 2022. A subset of 199 patients were included from our original study because they were alive and followed for recurrence past 2011.3
All tumor biopsies were reviewed by one of the principal authors (W.H.G. and A.B.C.) during the treatment selection process. SCCs were deemed aggressive if they exhibited perineural invasion (PNI), were poorly differentiated, or invaded subcutaneous tissue. BCCs were deemed aggressive if they exhibited PNI or were sclerosing, morpheaform, micronodular, or infiltrative histologic subtypes. Aggressive tumors were treated via MMS or referred to radiation oncology. Patients with at least one month of follow-up were included in the study and followed biannually or annually. Recurrences were defined as any malignancy histologically similar to the original tumor arising in or immediately around the radiation treatment field.3 The results are demonstrated in Table I.
Table I.
BCC, basal cell carcinoma; CI, confidence interval; HR, hazard ratio; SCC, squamous cell carcinoma.
| (N=2490) | ||||||||
|---|---|---|---|---|---|---|---|---|
|
|
||||||||
| 2-year recurrence (95% CI) | ate 5-year recurrence rate (95% CI) | 10-year recurrence rate (95% CI) | ||||||
| Type | ||||||||
| - All | 2.2% (1.5%-2.9%) | 6.0% (4.7%-7.4%) | 10.5% (7.8%-13.3%) | |||||
| - BCC | 2.8% (1.2%-4.4%) | 6.9% (3.8%-10.0%) | 12.4% (6.4%-18.5%) | |||||
| - SCC | 2.0% (1.2%-2.7%) | 5.8% (4.2%-7.3%) | 9.9% (6.8%-12.9%) | |||||
|
| ||||||||
| Univariate Analysis | Multivariate Analysis | |||||||
|
| ||||||||
| HR | 95% CI lower | 95% CI upper | P Value | HR | 95% CI lower | 95% CI upper | P Value | |
|
| ||||||||
| Age, years | 0.98 | 0.95 | 1 | 0.09 | 0.99 | 0.96 | 1.02 | 0.55 |
| Sex | ||||||||
| - Male† | ||||||||
| - Female | 0.53 | 0.33 | 0.86 | 0.01* | 0.59 | 0.36 | 0.98 | 0.04* |
| Type | ||||||||
| - BCC† | ||||||||
| - SCC | 0.86 | 0.56 | 1.32 | 0.48 | 0.45 | 0.06 | 3.37 | 0.44 |
| Stage | ||||||||
| - S0 (Tis)† | ||||||||
| - S1 (T1 or T2) | 1.1 | 0.72 | 1.69 | 0.66 | 0.46 | 0.06 | 3.3 | 0.44 |
| Site | ||||||||
| - Chin† | ||||||||
| - Nose | 2.21 | 1.14 | 4.28 | 0.02* | 2.16 | 1.08 | 4.3 | 0.03* |
| - Other | 0.88 | 0.41 | 1.92 | 0.75 | 0.85 | 0.39 | 1.86 | 0.69 |
| - Scalp | 2.59 | 1.31 | 5.15 | 0.01* | 2.12 | 1.04 | 4.3 | 0.04* |
| Size | ||||||||
| -≤2cm† | ||||||||
| - >2cm | 1.53 | 0.38 | 6.22 | 0.55 | 1.46 | 0.35 | 6.01 | 0.6 |
Reference groups in Cox analysis are Male, BCC, S0 (Tis), Chin, ≤2 cm.
Significant values (p<0.05) for lesions in males (p=0.04) and locations on the nose and scalp demonstrated higher rates of recurrence (p-values 0.03 and 0.04, respectively), which is likely attributable to increased ultraviolet radiation in those areas and/or less anatomic suitability for SXRT treatment. The predilection for males is not fully understood but is consistent with previous research. In contrast to our original study, we found no association between lesions 2 cm or larger (stage T2) and higher risk of recurrence in this study, likely due to the small sample of original tumors 2 cm or larger. Male-to-female was approximately 1:1. Mean age (SD) at time of treatment was 85.2 (6.6) years. Average duration of follow-up was 48.4 (40.3) months. Average time to recurrence following treatment was 37.8 (28.5) months. Average lesion size was 0.76 (0.53) cm x 1.0 (0.75) cm, and average lesion recurrence size was 0.73 (0.48) cm × 0.93 (0.68) cm. The average number of fractions, kV, and total dose was 5.47, 53.7, and 3566.1, respectively. The increased total number of tumors, longer follow-up duration, and advanced patient age likely accounts for the increase in recurrence rates compared to our original study.
There are various modalities in which dermatologists may approach the treatment of NMSC. While tailored treatment approaches are essential for all patients, particular emphasis is placed in the elderly population. Here, we demonstrate 2, 5, and 10-year tumor recurrence rates of 2.2%, 6.0%, and 10.5% over a span of 22 years, one of the longest and largest hypofractionated SXRT studies to date. We administered an average dose of 35.7 Gy over 5.47 fractions, while most treatment protocols utilize 40 to 45 Gy over 10 to 15 fractions (cost comparison available in Table II).5
Table II.
CPT, Current Procedural Terminology
| Type of treatment | Total cost (with corresponding CPT codes) |
|---|---|
|
| |
| Dermatologic office-based superficial radiation (5 fractions) | $734.67 (77280, 77300, 99212 x 4, 77401 x 4) |
| Dermatologic office-based superficial radiation (12 fractions) | $1610.30 (77290, 77300, 99212 x 11, 77401 x 11) |
| Mohs micrographic surgery (head/neck) with 1 additional stage and intermediate repair | $1396.16 (17311, 17312, 12051) |
Our study highlights the utility of hypofractionated SXRT as a well-tolerated and less expensive treatment alternative for select NMSCs in non-surgical patients. Further research should expand on the usage of hypofractionated scheduling in patients from underserved or low socioeconomic backgrounds who may also greatly benefit from reduced costs in treating NMSCs.
Abbreviations and Acronyms
- BCC
Basal cell carcinoma
- KM
Kaplan-Meier
- MMS
Mohs micrographic surgery
- NMSC
Non-melanoma skin cancer
- PNI
Perineural invasion
- SCC
Squamous cell carcinoma
- SD
Standard deviation
- SXRT
Superficial x-ray therapy
Footnotes
Conflicts of interest: None declared.
IRB approval: Exempted.
Data from this study has not been previously published. Consent for the publication of recognizable patient photographs or other identifiable material was obtained by the authors and included at the time of article submission to the journal stating that all patients gave consent with the understanding that this information may be publicly available.
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References
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