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

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

3. 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

4. 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

5. 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

6. BCC recurrence rates for Mohs’ Surgery StudyCommentsNo of PatientsCumm Recurr Rate (%) < 5 yr Cumm Recurr Rate (%) 5yr Julian and Bowers, 1997 1981-19951450.7- 0.8 Mohs, et al, 1988Ear10321.3- 1.7 Mohs, 1986Eyelid14830.5- 0.6 Lindgren, et al 2000Eyelid, medial canthus Mean f/u 49 mos 645* Roenigk et al, 1986F/u 2-4 yrs367**1.4* Robins, 19811483**1.8* Mohs, 19786187**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):1177-1183.” * Represents raw recurrence rate **Represents total number of tumors, not number of patients

7. BCC recurrence rates for Surgical Excision StudyCommentsNo of Patients Cumm Recurr Rate (%) < 5 yr Cumm Recurr Rate (%) 5yr Baur et al, 19774438.0 Germann et al, 19922723.2 Silverman et al, 19921955-19825884.8 Werlinger et al, 2002Private practice90**1.7 Van der Meer, 2001Frozen section analysis Mean f/u 59 mos 1081.9* 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

8. BCC recurrence rates for Cryosurgery StudyCommentsNo of Patients Cumm Rate (%) < 5 yr Cumm Rate (%) 5yr Nordin et al, 1997Nose, >10mm611.6-2.0 Lindgren and Larko, 1997 Eyelid2140 Anders et al 1995Eyelid2543.5 Fraunfelder et al, 1984Eyelid (<=10mm) Eyelid (> 10mm) 181 88 4.7 16.5 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

9. BCC recurrence rates for Curettage and Electrodesiccation StudyCommentsNo of Patients Cumm Recurr Rate (%) < 5 yr Cumm Recurr Rate (%) 5yr Kopf et al, 19771958-1962, trainees 1970 1962-1973, certified 597 91 210 18.8 9.6 5.7 Launis, 19933566.2* McDaniel, 1983Curettage only884.3- 8.5 Welinger et al, 2002Private practice102**3.7 Nordin, 1999Curettage-Cryosurg External ear 39**2.6 Nordin et al, 1997Curettage-Cryosurg Nose 502.0 Silverman et al, 19911955-1982, 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

10. 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%.

11. 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.