Tumor size is the most significant risk factor for local recurrence in dermatofibrosarcoma protuberans: A large-scale retrospective cohort analysis

To the Editor: Dermatofibrosarcoma protuberans (DFSP) is a rare, aggressive soft tissue sarcoma that affects the dermis, subcutaneous fat, and, in rare cases, muscle and fascia. Although, the metastatic rate of DFSP is low, the local recurrence rate is estimated to range from 2% to 21%.1Huis In ’t Veld E.A. van Coevorden F. Grünhagen D.J. et al.Outcome after surgical treatment of dermatofibrosarcoma protuberans: is clinical follow-up always indicated?.Cancer. 2019; 125: 735-741https://doi.org/10.1002/cncr.31924Crossref PubMed Scopus (29) Google Scholar Negative surgical margins are considered to be the most important prognostic factor for DFSP, as local recurrence can predispose to distant metastases.2Hao X. Billings S.D. Wu F. et al.Dermatofibrosarcoma protuberans: update on the diagnosis and treatment.J Clin Med. 2020; 9: 1752https://doi.org/10.3390/jcm9061752Crossref PubMed Scopus (61) Google Scholar Previous research on DFSP prognosis is centered on small cohorts and case series. We aimed to describe the demographics, tumor characteristics, and interventions of DFSP to determine risk factors for recurrence. We also analyzed the recurrence free survival, defined as time of diagnosis to recurrence or DFSP-specific death, whichever occurred first. Data for 7647 patients with histologically confirmed DFSP (ICD-0-3: codes 8832/8833) were collected from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program (18 registries, 2000-2018). After excluding those with missing information on race, anatomic site, and/or treatment modality, 4451 patients remained and 56 (1.26%) had recurrences. Of the 4451 patients, 52 (1.17%) had a DFSP-specific death. Descriptive demographic data are summarized in Supplementary Table I, available via Mendeley at https://doi.org/10.17632/mgw6hrhxm4.1. Univariate and multivariable logistic regression models were used to determine predictors of recurrence in patients with DFSP. Statistical analyses were conducted using SAS, version 9.4 (SAS Institute). In patients with recurrence, the median original tumor size was 3 cm (3 cm in nonrelapsing patients), and the median age of diagnosis was 42 years old (42 years in nonrelapsing patients). Age, sex, and marital status were significant risk factors in univariate analysis for risk of recurrence/DFSP-specified death (≥45 years: HR, 1.90; 95% CI, 1.29-2.79; P = .001) (unmarried: HR, 1.68; 95% CI, 1.12-2.54; P = .013) (male: HR, 2.32; 95% CI, 1.32-4.10; P = .004), but did not influence the risk in the multivariate analysis (Table I). In the multivariable model assessing for an association between age, sex, race, household income, and size, the risk of recurrence/DFSP-specified death in patients with large tumor size (≥3 cm) was 2.60 (95% CI: 1.30, 5.18) fold higher than in patients with small tumor size (P = .007) (Fig 1).Table IUnivariate proportional hazard Cox regressionVariableCategoryRecurrence/DFSP-specified deathTotalHR (95% CI)P-valueAge<45 y432381Ref≥45 y6520701.90 (1.29, 2.79).001SexFemale442385RefMale6420661.74 (1.19, 2.56).005RaceNon-Hispanic White562535RefOthers5219161.34 (0.92, 1.96).125Marital statusMarried392007RefNot Married5518051.68 (1.12, 2.54).013Household income≥$60,000763332Ref<$60,0003211181.46 (0.96, 2.21).074Anatomic siteTrunk502275RefHead/Neck205621.64 (0.97, 2.75).062Extremities3816141.03 (0.67, 1.57).901Size<3 cm111042Ref≥3 cm3011642.60 (1.30, 5.18).007Surgical modalityExcision933684RefMMS55310.48 (0.19, 1.17).106TreatmentSurgery only933986RefSurgery + Radiation only41940.85 (0.31, 2.31).748 Open table in a new tab Previous studies have had mixed findings on whether tumor size correlates to recurrence.1Huis In ’t Veld E.A. van Coevorden F. Grünhagen D.J. et al.Outcome after surgical treatment of dermatofibrosarcoma protuberans: is clinical follow-up always indicated?.Cancer. 2019; 125: 735-741https://doi.org/10.1002/cncr.31924Crossref PubMed Scopus (29) Google Scholar,3Kim M. Huh C.H. Cho K.H. Cho S. A study on the prognostic value of clinical and surgical features of dermatofibrosarcoma protuberans in Korean patients.J Eur Acad Dermatol Venereol. 2012; 26: 964-971https://doi.org/10.1111/j.1468-3083.2011.04190.xCrossref PubMed Scopus (20) Google Scholar In a cohort study of 197 patients, Li et al found that larger tumor size (>5 cm) was significantly associated with recurrence in the univariate analysis, but not in multivariate analysis.4Li Y. Wang C. Yang K. et al.Clinical features of dermatofibrosarcoma protuberans and risk factors for local recurrence after Mohs micrographic surgery.J Am Acad Dermatol. 2020; 82: 1219-1221https://doi.org/10.1016/j.jaad.2019.09.034Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar Our larger study suggested a greater tumor size to be significantly associated with recurrence even in multivariate analysis. More recently, Criscito et al5Criscito M.C. Martires K.J. Stein J.A. Prognostic factors, treatment, and survival in dermatofibrosarcoma protuberans.JAMA Dermatol. 2016; 152: 1365https://doi.org/10.1001/jamadermatol.2016.1886Crossref PubMed Scopus (51) Google Scholar demonstrated that larger tumor size (>3 cm) is associated with worse overall survival, which supports our findings. Limitations are that the SEER database contains limited data regarding select patient information. Additionally, SEER defines tumor size in some time periods as categorical variables in preset ranges, which may affect our ability to delineate a highly accurate median. However, the primary strength is a relatively large population in a rare disease. Due to the risk of recurrence in DFSP, identifying high risk patient populations is crucial along with careful examination and proactive follow-up. None disclosed.