Factors predictive of recurrence, metastasis, and death from primary basal cell carcinoma 2 cm or larger in diameter

doi:10.1016/j.jaad.2019.09.075

Journal of the American Academy of Dermatology

Volume 83, Issue 3, September 2020, Pages 832-838

https://doi.org/10.1016/j.jaad.2019.09.075 Get rights and content

Background

Basal cell carcinoma (BCC) recurrence and metastatic rates are known to be very low. The risk factors for these rare outcomes are subsequently not well studied.

Objective

To identify risk factors independently associated with local recurrence (LR) and metastasis and/or death (M/D) in large (≥2 cm) BCC.

Methods

BCCs histologically confirmed between 2000 and 2009 were retrospectively screened for tumor diameter at 2 academic centers. Medical records of all large BCCs and an equal number of randomly selected small BCCs were reviewed for LR and M/D.

Results

Included were 248 large BCC and 248 small BCC tumors. Large BCCs had a significantly higher risk of LR and M/D than small BCCs (LR: 8.9% vs 0.8%, P < .001; M/D: 6.5% vs. 0%, P < .001). Because the risks were so low in small BCCs, they were excluded from further analysis. On multivariable logistic regression, head/neck location (odds ratio [OR], 9.7; 95% confidence interval [CI], 3.0-31.3) and depth beyond fat (OR, 3.1; 95% CI, 1.0-9.6) were associated with LR in large BCCs. Risk of LR was lower with Mohs micrographic surgery (OR, 0.14; 95% CI, 0.04-0.5). Head/neck location (OR, 5.3; 95% CI, 1.2-23.2), tumor diameter ≥4 cm (OR, 11.9; 95% CI, 2.4-59.4), and depth beyond fat (OR, 28.6; 95% CI, 6.7-121) were significant predictors of M/D in large BCCs.

Limitations

Retrospective cohort design.

Conclusions

Large BCCs, particularly those with additional risk factors, have a high enough risk of recurrence and metastasis to warrant further investigation to optimize management.

Section snippets

Methods

Patients with a histologic diagnosis of BCC, BCC with focal squamous differentiation, or basosquamous carcinoma (together referred to as BCC) at Brigham and Women's Hospital and Massachusetts General Hospital were identified between January 1, 2000, and December 31, 2009. Included cases were surgically treated BCCs as determined by excision operative reports (MMS and non-MMS). Duplicate records were excluded. Recurrent tumors and tumors with no primary information were also excluded. If a tumor

Results

From 11,905 patients with BCC who were screened, 248 large BCC tumors (≥2 cm) were identified in 234 patients. The cohort of small BCC tumors (<2 cm) included 248 cases from 162 patients. The risk of LR and M/D in small BCCs was 0.8% and 0%, respectively, which was less than our 5% threshold, so small BCCs were excluded from further analyses.

The patient and tumor characteristics for disease-related outcomes are provided in Table I. There were 22 LRs and 16 M/Ds. Men had a 13% LR risk and 8% M/D

Discussion

Our results identify large BCCs (those with clinical diameter ≥2 cm) as having a 6.5% risk of M/D, which is more than 10-times higher than prior estimates of the risk of metastasis in BCC as a whole. Large BCCs also had a 9% risk of LR, which was significantly greater than the 0.8% risk in small BCCs. In addition, tumor diameter ≥4 cm, depth beyond fat, and head/neck location were predictors of M/D in large BCCs on multivariable analysis.

Most of the information on metastatic BCC (mBCC) is

Conclusion

The results reported here represent an important step toward the identification of a subset of BCC with a clinically significant risk of recurrence, metastasis, and death. BCC tumors with a diameter of at least 2 cm were found to have a 9% risk of LR and a 6.5% risk of M/D, which is significantly higher than that of the small BCC cohort and sufficient to warrant further investigation of optimal management. Prognostic factors, including tumor diameter ≥4 cm, head/neck location, and depth beyond

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Diagnosis of basal cell carcinoma (BCC) higher risk subtypes influences management strategies because of their propensity to recur locally. Subtyping is prone to inter-observer variability, and subtyping definitions are inconsistently applied. This study sought to compare the interobserver reproducibility of individual BCC subtypes using the 4th edition World Health Organization (WHO) Classification of Skin Tumours (CoST) definitions, with classification into lower and higher risk histological subtype groups.
Ninety-one BCC cases were rated by seven pathologists, noting the presence of BCC subtype(s), and providing a higher or lower risk subtype grouping per case. Raters were provided with definitions as per the 4th edition WHO CoST for 10 listed BCC subtypes. Surgical specimen type was noted. Subgroup analysis was performed to exclude cases when the tumour deep front was not well visualised, or there was tangential sectioning (n = 6). Light's kappa was used to assess inter-rater reliability.
From the total group (n = 91), five BCC subtypes showed a sufficient number of ratings for computing a κ statistic. From these five subtypes, superficial subtype showed substantial inter-rater agreement (κ = 0.64), and the other four subtypes showed moderate inter-rater agreement [nodular (κ = 0.45), sclerosing/morphoeic (κ = 0.45), infiltrating (κ = 0.49) and micronodular (κ = 0.57)]. Two-tiered rating into either higher or lower risk subtype showed substantial inter-rater agreement (κ = 0.72).
Our results suggest a need to more precisely define BCC subtypes. We suggest reporting BCC subtype using a two-tiered risk grouping, followed by specific subtypes present. Further studies examining the inter-rater reliability of less common BCC subtypes are required.
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Citation Excerpt :
Head and neck locations were nearly 12 times more likely to have metastasis or lead to death.32,35,37 In patients with BCC 2 cm or greater, the risk of metastasis and death in those with underlying nevoid basal cell carcinoma syndrome (NBCCS) is 50%, and in nonsyndromic patients with prior RT, the risk is 22%.37 Dermoscopy is a common clinical tool to aid in the identification of BCC.
Long-term outcomes of high-risk basal cell carcinoma treated with Mohs micrographic surgery
2022, JAAD International
A systematic review of observational management of cutaneous basal cell carcinoma
2022, Journal of Plastic, Reconstructive and Aesthetic Surgery
Cutaneous basal cell carcinoma (BCC) is the commonest cancer in the United Kingdom and United States. Surgical excision is the most common treatment. This review summarises all published outcomes of observational/non-interventional management of cutaneous BCC.
This PRISMA-compliant systematic review searched MEDLINE, EMBASE and CENTRAL databases from inception-June 2021. All studies reporting outcomes of observational management for BCC were included.
We identified 2529 titles, from which 4 full-text articles were eligible, reporting on 2298 individuals. Two studies were randomised controlled trials (RCTs) comparing histological clearance rates and adverse events following treatment with an inactive strategy (placebo cream) versus topical 5%-imiquimod (at different frequencies) for 6-12 weeks. Clearance rates ranged from 52-100% for imiquimod and 2-19% for placebo, with more adverse events associated with imiquimod. The other two studies used prospective cohort designs. One study assessed the natural history of BCCs managed expectantly in 39 individuals aged ≥80years. During the 15.8-month follow-up, 46.2% of lesions did not increase in size and 10.3% resolved. The remaining study compared treatment patterns of 1360 patients with non-melanoma skin cancer (NMSC) in individuals with or without limited life-expectancy (LLE). The LLE subgroup had a 5-year mortality rate of 43.3%, with no deaths attributed to NMSC. Only 3.3% of individuals with LLE underwent observational treatment. No study examined quality-of-life or cost-effectiveness.
There has been limited investigation of observational management of BCC, despite possible advantages of this strategy. Future RCTs should compare quality-of-life outcomes and utility-adjusted survival following interventional or observational management of BCC.

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: Funding sources: Genentech, Inc provided support for the conduct of this study. Mr Karia is supported by a Cancer Epidemiology, Prevention, and Control Training Grant from the National Cancer Institute of the National Institutes of Health (T32-CA-009314).

: Conflicts of interest: None disclosed.

: IRB approval status: The Partners Human Research Committee approved this study.

: Reprints not available from the authors.

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Original articleFactors predictive of recurrence, metastasis, and death from primary basal cell carcinoma 2 cm or larger in diameter

Background

Objective

Methods

Results

Limitations

Conclusions

Section snippets

Methods

Results

Discussion

Conclusion

Lancet Oncol

J Am Acad Dermatol

J Am Acad Dermatol

Lancet Oncol

Trends in basal cell carcinoma incidence and identification of high-risk subgroups, 1998-2012

JAMA Dermatol

Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the U.S. population, 2012

JAMA Dermatol

Cancer statistics, 2017

CA Cancer J Clin

Guidelines of care for the management of basal cell carcinoma

J Am Acad Dermatol

Long-term recurrence rates in previously untreated (primary) basal cell carcinoma: implications for patient follow-up

J Dermatol Surg Oncol

Original article
Factors predictive of recurrence, metastasis, and death from primary basal cell carcinoma 2 cm or larger in diameter