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Cutaneous basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) that have recurred after previous treatment are considered more difficult to cure compared with primary tumors, with overall 5-year re-recurrence rates reported as high as 15.4%1 for BCC and 5.9% for SCC.2 Few outcomes data exist from prospective studies, but a randomized controlled study in Europe of facial BCCs found that 5-year recurrence rates after excision or Mohs surgery for 397 primary tumors varied from 2.5% to 4.1%, compared with 2.4% to 12.1% for 202 recurrent tumors.3 The generalizability of these results to the United States, to other BCCs and SCCs, and after treatments delivered in the community is not clear. We sought to determine the 5-year recurrence rate after treatment of a consecutive cohort of BCCs and SCCs already recurrent at presentation.
The design of this prospective observational cohort study has been described4; this research was approved by the committee on human research, University of California, San Francisco. All 1536 patients with 1993 BCCs or SCCs in 1999 through 2000 at a university-based private practice or the dermatology clinics at the affiliated Veterans Affairs Medical Center (VA) were enrolled. We eliminated tumors in patients with basal cell nevus syndrome and restricted the sample to tumors treated with the 3 main therapies: electrodessication and curettage (EDC), elliptical excision, or Mohs surgery. Analysis was limited to patients with follow-up after treatment (93.8%). In this report we compare 126 patients with 137 tumors that were recurrent at presentation with 1174 patients with 1488 primary tumors. Treatment of the primary tumors has been described.4 Of the recurrent tumors, 13 were treated with EDC, 51 with excision, and 73 with Mohs surgery; 2 recurrent tumors initially treated with excision were retreated with Mohs surgery when tumor was found to be present at the margins of the surgical specimen. Overall, patients with primary tumors were followed for a median of 7.4 years (interquartile range [IQR], 3.0–8.8 years] and recurrent tumors for 7.9 years (IQR, 3.2–8.9 years). Data about recurrence were collected by study staff blinded as much as possible to treatment type. The primary source of data about recurrence was the medical record, supplemented by physical examination by the study dermatologist for patients who consented to participate.
Characteristics5 in the primary and initially recurrent groups were compared using χ2 or Fisher exact tests for categorical variables and Mann-Whitney U tests for continuous variables. Unadjusted recurrence rates were calculated using the Kaplan-Meier method. Data were right-censored at the last date of care. Survival functions were compared using the log-rank test.
At enrollment, patients with recurrent tumors were similar (P>.05) to those with primary tumors (mean age, 69.0 years; 76.9% were male). Compared with primary tumors, recurrent tumors were similar in body location and likelihood of being in the H-zone of the face but were more often BCCs (75.6% vs 83.2%; P=.04),were larger (8.0 mm vs 10.0 mm, P=.03), and were more likely to have histopathologic risk factors for recurrence4 (20.4% vs 29.9%; P=.009). Also, recurrent tumors differed in the 3 treatment groups; for example, those treated with Mohs surgery were more likely to be BCC (P=.04) and located in the H-zone of the face (P<.001).
Over the follow-up period, 8 recurrent tumors re-recurred (5.8% [95% CI, 1.9%–9.8%]): 3 after excision and 5 after Mohs surgery. No recurrent tumors treated with EDC re-recurred. Details about the 8 recurrent tumors that re-recurred are presented in the Table; 87.5% of tumors that re-recurred were BCCs, and 37.5% were in the H-zone of the face. The median time for detection of recurrence was 1.3 years for recurrent tumors (IQR, 0.97–4.6) and 3.9 years for primary tumors (IQR, 1.8–5.3) (P=.15). Overall, the unadjusted 5-year recurrence rate calculated using survival analysis techniques was 5.1% for recurrent tumors (95% CI, 2.3%–11.0%) vs 3.4% for primary tumors (95% CI, 2.4% –4.6%) (P=.18). The Figure depicts Kaplan-Meier curves of tumor recurrence for primary and recurrent tumors.
To our knowledge, this study is the largest prospective cohort study in the United States examining long-term re-recurrence of recurrent BCCs and SCCs treated with the 3 most common treatments. Tumors in the treatment groups differed in severity, and given the small number of recurrences overall we cannot compare effectiveness after different therapies or adjust for other risk factors. The results suggest, however, that overall re-recurrence rates of already recurrent BCCs and SCCs treated in the community may be less than conventionally believed.
Funding/Support: This work was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (grant No. K24 AR052667).
Author Contributions: All authors had full access to the data in this report and take responsibility for its integrity and the accuracy of the analysis. Study concept and design: Chren. Acquisition of data: Stuart and Chren. Analysis and interpretation of data: Hamilton and Parvataneni. Drafting of the manuscript: Hamilton and Chren. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Hamilton, Parvataneni, and Chren. Obtained funding: Chren. Administrative, technical, and material support: Stuart. Study supervision: Hamilton and Chren.
Conflict of Interest Disclosures: Dr Chren is a consultant for Genentech Inc.