Official Title: “Prospective Randomized Trial: Curettage Versus Excision in Nodular and Superficial Basal Cell Carcinomas”

Basal cell carcinoma (BCC) is the most frequent skin cancer. Uncontrolled growth destroys local anatomic structures. There are various treatment alternatives with different recurrence rates and expenses. After surgical excision, the recurrence rate is in between 3 and 4% and the procedure is relatively expensive. Photodynamic therapy as well as imiquimod 5% are expensive therapies with high recurrence rates, that lack histologic evidence of BCC.

Cryosurgery and curettage are inexpensive, although the recurrence rates are higher than after surgical excision.

This prospective, randomized trial compares recurrence rates, cosmetic outcome, and surgery-related complications after curettage versus surgical excision in nodular and superficial BCC. About 600 tumors will be included. One half is treated by curettage, the other half by surgical excision. The follow-up period is four years. If the difference between recurrence rates is ≤7% and the cosmetic outcome as well as the surgery-related complications are not worse after curettage, surgical excision must be considered an overtreatment.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2013

1. First presentation of a patient with clinical or histopathological diagnosis of BCC

2. Study patient number, first and surname, date of birth and gender are listed in a distinct file.

3. Informed consent

4. Whole body screening for skin cancer

5. In- or exclusion of the patient. If the patient is excluded, no more data are obtained.

6. Recording of the following features in an electronic file:

1. Number of BCCs

2. Anatomic location - Lip - Eyelid - Ear - Nose - Other parts of the face - Scalp or neck - Trunk - Arm, hand, or shoulder - Leg, foot, or hip

3. Position - Ventral or dorsal. If the tumor is located at the lateral margin of ventral and dorsal, it is considered ventral. - Right, left, midline - Distinct BCCs are numbered. To ensure future distinction of different tumors, numbering starts with the most up-right-ventral tumor and ends with the most down-left-dorsal one. Numbering continues with BCCs that appear later during the period of recruitment.

4. Diameter in mm

7. In- or exclusion of the tumor

8. Photographs of the included BCCs

9. Randomization is performed by the Department of Biostatistics (distance to the Department of Dermatology = 1.7 km) with envelopes containing the assigned study arm.

The study physician calls one of four staff members of the Department of Biostatistics and asks for randomization. The envelopes are not opened unless the electronic data file is completed by the study physician.

10. Disinfection

11. Local anesthesia

12. Surgery

13. Dressing

14. If histopathology discovers another BCC type than nodular or superficial or even another tumor than BCC, then the tumor is excluded.

15. Follow-up visit 3 and 6 months (+/- 30 days) after the operation. In BCCs that had to be operated in >1 step, the day of the follow-up visit refers to the initial operation.

16. In case of clinical suspicion of recurrence of BCC a punch biopsy is taken. If the biopsy confirms recurrence, the endpoint is achieved.

17. If BCCs must be added to a patient during the recruitment period, follow-up visits always refer to the latest BCC.

18. If the patient visits our department not within the defined follow-up period, the appointment is not recorded (except confirmation of recurrence).

19. Patients who provide no feedback receive phone calls.

20. If a patient or a private practitioner suspect a recurrence of BCC beyond a defined follow-up period, of course, the patient is invited as early as possible to our department, where a biopsy will be taken.

21. The patient receives a letter containing a list of the BCCs treated within the study.

The private practitioner is to be visited with the list after 12, 24, and 36 months (+/- 30 days) referring to the last operation within the recruitment period. The letter contains a questionnaire about scar size and suspicion of recurrence of BCC. The practitioner or the patient return the questionnaire with the answers to our department.

If recurrence is suspected we take a biopsy.

22. When follow-up is closed for an individual patient, the reason is recorded:

1. Planned end of follow-up after 48 months.

2. Patient has moved.

3. Death (date of death).

4. Consent withdrawn.

5. Patient has become meanwhile so ill or high-maintenance that no more follow-up visits can be planned.

6. Recurrence of all of the patient's BCCs.

23. Statistic evaluation is based on an intention-to-treat-analysis.

24. The trial is designed to prove the equivalence of treatment modalities. A statistic test is used for evaluation, including the Kaplan-Meier-method. When all 4 study arms contain 116 BCCs, a 2-group-test on the equivalence of ratios with a 1-sided significance level of 0.05 will have a power of 80% to disprove the null hypothesis. The null hypothesis is that standard and test method are not equivalent (ratio difference delta T - delta S ≥ 0.15). Then the alternative hypothesis is more probable, meaning that the ratios in both groups are equivalent supposed that the expected ratio difference is 0.07 and the ratio within the standard group is 0.03 (according to an expected recurrence rate of 3% in the surgical excision study arm).

Intervention(s) in this Clinical Trial

• Procedure: Curettage
  • Curettage without subcutaneous tissue using a 7 mm ring curette and the "fountain-pen technique" (http://www.biopsypunch.com/kuerettagetechnik.htm; accessed on March 13, 2008). The curette is held between the thumb, index and middle finger. This method of holding enables precise guiding of the instrument, so that the piece of tissue can be removed in one well-targeted incision. After macroscopically complete removal, a safety margin is removed with the curette. It is used for histology to distinguish between R0 (excision margin without tumor cells) and R1 resection (excision margin containing tumor cells). Preparation with paraffin. Parallel, vertical sections for histologic diagnosis. Hematoxylin-eosin staining. Measurement of tumor thickness in mm.
• Procedure: Deep excision
  • 12 o'clock mark. Excision with a scalpel down to the subcutaneous level. Plastic reconstruction. Three vertical, parallel bread loaf sections for histology. Preparation with paraffin. Staining with hematoxylin-eosin. Histologic diagnosis including report of tumor thickness in mm. Comment on complete removal (R0 versus R1). In case of R1 excision directed reoperations are performed until R0 is achieved.
• Procedure: Shave excision
  • Shave excision with a safety margin, using a scalpel. Wound healing by secondary intention. Preparation with paraffin. Parallel vertical bread loaf sections for histology. Staining with hematoxylin-eosin. Histologic diagnosis. Comment on complete removal (R0 versus R1). In case of R1 excision a reoperation is performed until R0 is achieved.
• Procedure: Curettage
  • Curettage with a 7 mm ring curette with the "potato-peeler technique" (http://www.biopsypunch.com/kuerettagetechnik.htm; accessed on March 13, 2008). The handle of the curette is held in the distal inter-digital fold of the index finger, and supported by the other fingers of the curetting hand. The thumbs serve to provide a stable base. This technique makes it possible to guide the instrument, applying greater pressure, but accuracy is reduced. After macroscopically complete removal, a safety margin is removed with the curette. It is used for histology to distinguish between R0 (excision margin without tumor cells) and R1 resection (excision margin containing tumor cells). Preparation with paraffin. Parallel, vertical sections for histologic diagnosis. Hematoxylin-eosin staining.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Clinical or histologic diagnosis of nodular BCC
• Active Comparator: 2
  • Clinical or histologic diagnosis of nodular BCC
• Experimental: 3
  • Clinical or histologic diagnosis of superficial BCC
• Active Comparator: 4
  • Clinical or histologic diagnosis of superficial BCC

Primary Measures

• Recurrence of BCC, confirmed by biopsy
  • Time Frame: 4 years after surgery
    Safety Issue?: Yes

Secondary Measures

• Secondary hemorrhage as remembered by the patient
  • Time Frame: 3 months (plus or minus 30 days) after surgery
    Safety Issue?: Yes
• Wound infection as remembered by the patient
  • Time Frame: 3 months (plus or minus 30 days) after surgery
    Safety Issue?: Yes
• Hypesthesia after surgery
  • Time Frame: 3 months (plus or minus 30 days) after surgery
    Safety Issue?: No
• Keloid
  • Time Frame: 3 months (plus or minus 30 days) after surgery
    Safety Issue?: No
• Functional impairment or disfigurement by the scar. Keloid is always a disfiguring scar. If the scar is recognized as keloid, the measure "disfigurement" cannot be used here.
  • Time Frame: 3 months (plus or minus 30 days) after surgery
    Safety Issue?: No
• Subjective assessment of the esthetic outcome of the scar on a scale of excellent, good, satisfying, moderate, unfavorable; done by the patient
  • Time Frame: 3, 6, 12, 24, 36, and 48 months (plus or minus 30 days) after surgery
    Safety Issue?: No
• Subjective assessment of the esthetic outcome of the scar on a scale of excellent, good, satisfying, moderate, unfavorable; done by the study physician
  • Time Frame: 3, 6, 12, and 48 months (plus or minus 30 days) after surgery
    Safety Issue?: No
• Subjective assessment of the esthetic outcome of the scar on a scale of excellent, good, satisfying, moderate, unfavorable; done by a private practitioner
  • Time Frame: 12, 24, and 36 months (plus or minus 30 days) after surgery
    Safety Issue?: No
• Scar length in mm
  • Time Frame: 6 and 48 months (plus or minus 30 days) after surgery
    Safety Issue?: No
• Scar width in mm, perpendicular to its length
  • Time Frame: 6 and 48 months (plus or minus 30 days) after surgery
    Safety Issue?: No
• Color of the scar: hyperpigmented, hypopigmented, or erythematous
  • Time Frame: 6 and 48 months (plus or minus 30 days) after surgery
    Safety Issue?: No
• Level of the scar: atrophic, skin level, hypertrophic, or keloid
  • Time Frame: 6 and 48 months (plus or minus 30 days) after surgery
    Safety Issue?: No

Inclusion Criteria:

• Clinical or histologic diagnosis of BCC

Patient Dependent Exclusion Criteria:

• > 5 BCCs at presentation
• Immunosuppressive drugs
• Pregnancy
• Disability to give informed consent
• Synchronous participation in other studies
• Progeroid syndromes
• Other malignant tumors, except for BCC and squamous cell carcinoma, or monoclonal neoplasms of the hematopoietic or immune system
• Critical illness precluding sufficient follow-up visits

Tumor Exclusion Criteria:

• Recurrent BCC
• Nodular BCC with an exophytic part of > 1.5 mm above skin level
• Nodular BCC with a diameter of > 10 mm
• Superficial BCC with a diameter of > 20 mm
• Ulceration
• Scarring
• Blurred margins
• Histopathologic evidence of a tumor type different from nodular or superficial BCC

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University Hospital Tuebingen

Overall Clinical Trial Officials and Contacts

Helmut Breuninger, M.D. Study Chair Department of Dermatology, Eberhard Karls University Tuebingen  

Overall Contact: Helmut Breuninger, M.D. +49-70 71-29 helmut.breuninger@med.uni-tuebingen.de

Information obtained from ClinicalTrials.gov on August 28, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00515970

Study ID Number: E.03.26007.1

ClinicalTrials.gov Identifier: NCT00515970

Health Authority: Germany: Federal Ministry of Education and Research