Presented by Robert S. Stern, M.D. at the September 10, 2003 meeting of the Dermatologic and Ophthalmic Drugs Advisory Committee

Recurrence Rates in Primary Basal Cell Carcinoma According to Treatment Modality Jean C. Lee, Harvard Medical Student

Treatment Modalities for Basal Cell Carcinoma Usually reserved for small (<2cm), well- defined tumors on low risk areas, performed with 4-5 mm margins Surgical Excision Cryosurgery Curettage and Electrodesiccation Mohs' Micrographic Surgery Usually reserved for tumors < 1 cm on cosmetically less sensitive areas Usually for low risk lesions on trunk or extremities Reserved for high risk tumors, including: Size 5-10mm in H zone of face, >10 mm on rest of face, or > 20 mm on body Tumors with no distinct margins High risk histology (morpheaform or infiltrative BCC) Persistently recurrent tumors

Predictors of BCC Recurrence Size of tumor Clinically indistinct margins Location (embryonic fusion planes provide little resistance to tumor growth) Histologic type (morpheaform, micronodular, sclerosing, or mixed type) Perineural invasion Recurrent tumor Previously irradiated tumor Skill of the operator

Defining Recurrence Rates Raw recurrence rate: total number of recurrences divided by the total number of tumors treated Strict recurrence rate: total number of patients with recurrence divided by number of treated patients observed for at least 5 years Life table cumulative 5 year recurrence rate: Adjusts recurrence rates for the number of patients lost to follow-up each year

BCC recurrence rates for Mohs’ Surgery StudyCommentsNo of PatientsCumm Recurr Rate (%) < 5 yr Cumm Recurr Rate (%) 5yr Julian and Bowers, Mohs, et al, 1988Ear Mohs, 1986Eyelid Lindgren, et al 2000Eyelid, medial canthus Mean f/u 49 mos 645* Roenigk et al, 1986F/u 2-4 yrs367**1.4* Robins, **1.8* Mohs, **0.7* Data from Thissen M et al. “A Systematic Review of Treatment Modalities for Primary Basal Cell Carcinomas”, Archives of Dermatology 1999;135(10): ” * Represents raw recurrence rate **Represents total number of tumors, not number of patients

BCC recurrence rates for Surgical Excision StudyCommentsNo of Patients Cumm Recurr Rate (%) < 5 yr Cumm Recurr Rate (%) 5yr Baur et al, Germann et al, Silverman et al, Werlinger et al, 2002Private practice90**1.7 Van der Meer, 2001Frozen section analysis Mean f/u 59 mos * Spraul et al, 2000Periocular Mean f/u 31.3 mos 141**11.8* pos margins 2.3* neg margins Rowe et al, 1989Metanalysis (27)5560**2.8* Rowe et al, 1989Metanalysis (10)2606**10.1* *Represents raw recurrence rate **Represents total number of tumors, not number of patients

BCC recurrence rates for Cryosurgery StudyCommentsNo of Patients Cumm Rate (%) < 5 yr Cumm Rate (%) 5yr Nordin et al, 1997Nose, >10mm Lindgren and Larko, 1997 Eyelid2140 Anders et al 1995Eyelid Fraunfelder et al, 1984Eyelid (<=10mm) Eyelid (> 10mm) Kuflik and Gage, 1991Single provider628*1.0 Rowe et al, 1989Metanalysis (13)2462**3.7* Rowe et al, 1989Metanalysis (1)269**7.5* * Represents raw recurrence rate **Represents total number of tumors, not number of patients

BCC recurrence rates for Curettage and Electrodesiccation StudyCommentsNo of Patients Cumm Recurr Rate (%) < 5 yr Cumm Recurr Rate (%) 5yr Kopf et al, , trainees , certified Launis, * McDaniel, 1983Curettage only Welinger et al, 2002Private practice102**3.7 Nordin, 1999Curettage-Cryosurg External ear 39**2.6 Nordin et al, 1997Curettage-Cryosurg Nose Silverman et al, , includes lesions > 10 mm 2258**8.6 (low risk) 12.9 (med risk) 17.5 (high risk) Rowe et al, 1989Metanalysis (12)3664**4.7* Rowe et al, 1989Metanalysis (10)3573**7.7* Dubin and Kopf, 1983Trainees758**26.0

Summary The range of recurrence rates appear to be similar for most physical modalities, including surgical excision, cryosurgery, curettage and electrodesiccation, curettage and cryosurgery, and curettage alone. For follow-up period of 3-4 years, this rate falls between 3 to 5% For a follow-up period of 5 years or more, this rate is about double, approximately 5 to 12% Recurrence rates for tumors treated by Moh’s Micrographic Surgery appear to be lower at all points in time and averages between 1-2%.

Conclusions The key predictors of tumor recurrence are size and site of the lesion, histology of tumor, and skill of the operator All of the non-Mohs' modalities have roughly equal and excellent cure rates for BCC without high-risk prognostic factors There is an increased risk of BCC recurrence regardless of treatment modality with increasing time. This underscores the importance of long term follow-up for evaluating the effectiveness of a therapy.