Superficial Basal Cell Carcinoma
Conditions
Keywords
Methyl aminolevulinate, Photodynamic therapy, Primary Superficial Basal Cell Carcinoma
Brief summary
The purpose of this study was to compare the efficacy of Photodynamic Therapy (PDT) methyl aminolevulinate (MAL) cream to cryotherapy, in treatment of participants with primary superficial basal cell carcinoma (BCC). Secondary objectives was to compare cosmetic outcome and tolerability (adverse events) in these participants, 3 months after treatment. In addition the recurrence rates in the two treatment groups will be compared up to five years after treatment.
Detailed description
BCC was a highly frequent skin malignancy, and accounts for approximately 75% of all non-melanoma skin cancers. It is the most common malignant tumour of any organ, mostly affecting head and neck (84%) in fair-skinned people. Several non-pharmacological treatment modalities was used for BCC, including excision surgery, Moh's surgery, radiation, curettage/electrodesiccation and cryotherapy. The treatment used depends on the type, size, depth and localisation of the BCC lesion. The use of PDT was attractive for the treatment of BCCs because of its efficiency, mild and local side effects and excellent cosmetic outcome. Previous clinical experience was promising and participants with primary BCCs were included in this prospective, randomised, comparative, multicenter study to show that Metvix is non-inferior to alternative treatment with better cosmetic outcome. The primary end-point is the number of participants in whom 75% or more of the BCC lesions have responded completely at 3 months after PDT with Metvix or 3 months after cryotherapy. Both on-site and independent, blinded response assessments analysed. The analysis based on the results of the independent review board constitutes the primary analysis. The secondary end-points was the proportion of participants in whom less than 75% of the BCC lesions respond completely, number of lesions across participants that show complete response, evaluation of cosmetic outcome and adverse events 3 months after Metvix PDT or 3 months after cryotherapy. In addition 12, 24, 36, 48 and 60 months recurrence rates was assessed.
Interventions
DRUGMetvix® cream
PROCEDUREHand held liquid nitrogen spray cryotherapy
Sponsors
Galderma R&D
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
A participant with superficial BCC lesion(s) suitable for entry was defined as a participant with: * histologically confirmed diagnosis of primary superficial BCC lesion(s) * BCC lesions suitable for cryotherapy * males or females above 18 years of age * written informed consent. In accordance with Amendment 2 (local amendment), only participant above 19 years of age were to be included in Austria.
Exclusion criteria
A participant or lesion fulfilling any of the following criteria was ineligible for inclusion: * prior treatment of the BCC lesion(s) * participant with more than 10 eligible BCC lesions * a superficial BCC lesion with the largest diameter exceeding 15 mm on face/scalp, larger than 20 mm on extremities and neck and larger than 30 mm on the trunk * a superficial BCC lesion with the largest diameter smaller than 6 mm * participant with porphyria * participant with Gorlin's syndrome * pigmented superficial BCC lesion(s) * morpheaform lesion(s) * infiltrating lesion(s) * participants with a history of arsenic exposure * known allergy to Metvix®, a similar PDT compound or excipients of the cream * participation in other clinical studies either concurrently or within the last 30 days * pregnant or breast-feeding; all women of child-bearing potential had to document a negative pregnancy test and use the pill or intrauterine device during the treatments and for at least one month thereafter * conditions associated with a risk of poor protocol compliance. In Amendment 1 the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Histologically Confirmed Patient Complete Response (CR) 3 Months After Last Metvix PDT or Cryotherapy Cycle | 3 months after last Metvix PDT or Cryotherapy cycle, up to 6 months | Patient Complete Response (CR) was defined as 100 percentage of the lesions within the participant having negative findings for nodular basal cell carcinoma (BCC) in the histological examination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Lesion With Complete Response 3 Months After Last Metvix PDT or Cryotherapy Cycle | 3 months after last Metvix PDT or Cryotherapy cycle, up to 6 months | Complete response was defined as no clinically visible BCC lesions in the treatment area. |
| Overall Cosmetic Outcome Assessed by Investigator 3 Months After the Last Metvix PDT or Cryotherapy Cycle | 3 months after the last metvix PDT or Cryotherapy cycle (Up to 6 months) | Cosmetic outcome was assessed by both investigator and participants in participants with 100% of lesions in complete response. Overall cosmetic outcome was assessed with regard to occurrence of the following signs or symptoms; scarring, atrophy, induration, redness or change in pigmentation. The investigator graded the cosmetic outcome as: * excellent: no scarring, atrophy or induration, and no or slight occurrence of redness or change in pigmentation compared lo adjacent skin * good: no scarring, atrophy or induration but moderate redness or change in pigmentation compared to adjacent skin * fair: slight to moderate occurrence of scarring, atrophy or induration * poor: extensive occurrence of scarring, atrophy or induration. |
| Overall Cosmetic Outcome Assessed by Participants 3 Months After the Last Metvix PDT or Cryotherapy Cycle | 3 months after the last metvix PDT or Cryotherapy cycle (Up to 6 months) | Cosmetic outcome was assessed by both investigator and participants in participants with 100% of lesions in complete response. Overall cosmetic outcome was assessed with regard to occurrence of the following signs or symptoms; scarring, atrophy, induration, redness or change in pigmentation. The participants graded the cosmetic outcome as: * excellent: no scarring, atrophy or induration, and no or slight occurrence of redness or change in pigmentation compared lo adjacent skin * good: no scarring, atrophy or induration but moderate redness or change in pigmentation compared to adjacent skin * fair: slight to moderate occurrence of scarring, atrophy or induration * poor: extensive occurrence of scarring, atrophy or induration. |
| Recurrence Rate in Complete Clearance Group | 12, 24, 36, 48 and 60 months after last Metvix PDT cycle or Cryotherapy (Up to 5 years) | Recurrence rate in complete clearance group was analyzed. |
| Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | 24, 36, 48, and 60 Months After the Last Metvix PDT Cycle (Up to 5 years) | Cosmetic outcome was assessed by both investigator and participants in participants with 100% of lesions in complete response. Overall cosmetic outcome was assessed with regard to occurrence of the following signs or symptoms; scarring, atrophy, induration, redness or change in pigmentation. The investigator graded the cosmetic outcome as: * excellent: no scarring, atrophy or induration, and no or slight occurrence of redness or change in pigmentation compared lo adjacent skin * good: no scarring, atrophy or induration but moderate redness or change in pigmentation compared to adjacent skin * fair: slight to moderate occurrence of scarring, atrophy or induration * poor: extensive occurrence of scarring, atrophy or induration. |
Countries
Austria, Belgium, Finland, France, Italy, Sweden, United Kingdom
Participant flow
Recruitment details
A total of 120 participants were randomized, of which 118 were received the study treatment. The study was carried out in 13 centers in seven European countries, they were included (Sweden, Finland, United Kingdom, Austria, France, Belgium and Italy).
Participants by arm
| Arm | Count |
|---|---|
| Metvix® PDT Participants with basal cell carcinoma (BCC) lesions were administered to photodynamic therapy (PDT) with Metvix® cream 160 milligrams per gram (mg/g) applied for three hours, followed by illumination using non-coherent light with a fluency of 75 Joule per centimeter square (J/cm\*2) and fluency rate of 70-200 milliwatt per centimeter square (mW/cm\*2) up to 13 weeks. | 60 |
| Cryotherapy Cryotherapy was performed with a hand-held liquid nitrogen spray, using a double freeze-thaw cycle. After an initial icefield formation with a 3 millimeter (mm) rim of clinically healthy tissue, the icefield was to be maintained for a minimum of 20 seconds. This procedure was repeated after a thaw of 2-3 times the freeze time up to 12 weeks. | 58 |
| Total | 118 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 2 |
| Overall Study | Consent withdrawn | 1 | 1 |
| Overall Study | Intercurrent disease | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Randomized but not treated | 2 | 0 |
| Overall Study | Treatment failure all lesions | 18 | 11 |
Baseline characteristics
| Characteristic | Metvix® PDT | Cryotherapy | Total |
|---|---|---|---|
| Age, Continuous | 63 Years STANDARD_DEVIATION 16 | 64 Years STANDARD_DEVIATION 13 | 64 Years STANDARD_DEVIATION 15 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 60 Participants | 58 Participants | 118 Participants |
| Sex: Female, Male Female | 20 Participants | 28 Participants | 48 Participants |
| Sex: Female, Male Male | 40 Participants | 30 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 60 | 3 / 58 |
| other Total, other adverse events | 0 / 60 | 0 / 58 |
| serious Total, serious adverse events | 7 / 60 | 2 / 58 |
Outcome results
Primary
Percentage of Participants With Histologically Confirmed Patient Complete Response (CR) 3 Months After Last Metvix PDT or Cryotherapy Cycle
Patient Complete Response (CR) was defined as 100 percentage of the lesions within the participant having negative findings for nodular basal cell carcinoma (BCC) in the histological examination.
Time frame: 3 months after last Metvix PDT or Cryotherapy cycle, up to 6 months
Population: Intent-to-treat analysis set included all the participants enrolled in the study who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Metvix® PDT | Percentage of Participants With Histologically Confirmed Patient Complete Response (CR) 3 Months After Last Metvix PDT or Cryotherapy Cycle | 92 percentage of participants |
| Cryotherapy | Percentage of Participants With Histologically Confirmed Patient Complete Response (CR) 3 Months After Last Metvix PDT or Cryotherapy Cycle | 90 percentage of participants |
Secondary
Number of Lesion With Complete Response 3 Months After Last Metvix PDT or Cryotherapy Cycle
Complete response was defined as no clinically visible BCC lesions in the treatment area.
Time frame: 3 months after last Metvix PDT or Cryotherapy cycle, up to 6 months
Population: Intent-to-treat analysis set included all the participants enrolled in the study who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Metvix® PDT | Number of Lesion With Complete Response 3 Months After Last Metvix PDT or Cryotherapy Cycle | 109 lesion |
| Cryotherapy | Number of Lesion With Complete Response 3 Months After Last Metvix PDT or Cryotherapy Cycle | 94 lesion |
Secondary
Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle
Cosmetic outcome was assessed by both investigator and participants in participants with 100% of lesions in complete response. Overall cosmetic outcome was assessed with regard to occurrence of the following signs or symptoms; scarring, atrophy, induration, redness or change in pigmentation. The investigator graded the cosmetic outcome as: * excellent: no scarring, atrophy or induration, and no or slight occurrence of redness or change in pigmentation compared lo adjacent skin * good: no scarring, atrophy or induration but moderate redness or change in pigmentation compared to adjacent skin * fair: slight to moderate occurrence of scarring, atrophy or induration * poor: extensive occurrence of scarring, atrophy or induration.
Time frame: 24, 36, 48, and 60 Months After the Last Metvix PDT Cycle (Up to 5 years)
Population: Intent-to-treat analysis set included all the participants enrolled in the study who received at least one dose of study treatment. Here overall Number of participants analyzed signifies those participants who were evaluable for this outcome measure. Number analyzed, signifies those participants who were evaluable for this outcome measure at the specified time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Excellent: At month 24 | 19 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Fair: At month 36 | 4 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Good: At month 36 | 12 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Poor: At month 36 | 0 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Excellent: At month 48 | 19 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Good: At month 48 | 10 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Fair: At month 48 | 4 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Good: At month 24 | 12 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Excellent: At month 60 | 18 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Fair: At month 24 | 3 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Good: At month 60 | 8 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Excellent: At month 36 | 20 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Poor: At month 48 | 0 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Poor: At month 60 | 0 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Fair: At month 60 | 6 Participants |
| Cryotherapy | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Poor: At month 60 | 1 Participants |
| Cryotherapy | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Good: At month 24 | 15 Participants |
| Cryotherapy | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Fair: At month 24 | 20 Participants |
| Cryotherapy | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Excellent: At month 36 | 5 Participants |
| Cryotherapy | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Excellent: At month 48 | 5 Participants |
| Cryotherapy | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Good: At month 48 | 21 Participants |
| Cryotherapy | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Fair: At month 48 | 15 Participants |
| Cryotherapy | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Good: At month 36 | 22 Participants |
| Cryotherapy | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Fair: At month 36 | 14 Participants |
| Cryotherapy | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Poor: At month 36 | 2 Participants |
| Cryotherapy | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Poor: At month 48 | 1 Participants |
| Cryotherapy | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Excellent: At month 60 | 6 Participants |
| Cryotherapy | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Good: At month 60 | 22 Participants |
| Cryotherapy | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Fair: At month 60 | 14 Participants |
| Cryotherapy | Overall Cosmetic Outcome Assessed by Investigator 24, 36, 48, and 60 Months After the Last Metvix PDT or Cryotherapy Cycle | Excellent: At month 24 | 3 Participants |
Secondary
Overall Cosmetic Outcome Assessed by Investigator 3 Months After the Last Metvix PDT or Cryotherapy Cycle
Cosmetic outcome was assessed by both investigator and participants in participants with 100% of lesions in complete response. Overall cosmetic outcome was assessed with regard to occurrence of the following signs or symptoms; scarring, atrophy, induration, redness or change in pigmentation. The investigator graded the cosmetic outcome as: * excellent: no scarring, atrophy or induration, and no or slight occurrence of redness or change in pigmentation compared lo adjacent skin * good: no scarring, atrophy or induration but moderate redness or change in pigmentation compared to adjacent skin * fair: slight to moderate occurrence of scarring, atrophy or induration * poor: extensive occurrence of scarring, atrophy or induration.
Time frame: 3 months after the last metvix PDT or Cryotherapy cycle (Up to 6 months)
Population: Intent-to-treat analysis set included all the participants enrolled in the study who received at least one dose of study treatment. Here overall Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 3 Months After the Last Metvix PDT or Cryotherapy Cycle | Investigator: Excellent | 17 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 3 Months After the Last Metvix PDT or Cryotherapy Cycle | Investigator: Good | 30 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Investigator 3 Months After the Last Metvix PDT or Cryotherapy Cycle | Investigator: Fair | 6 Participants |
| Cryotherapy | Overall Cosmetic Outcome Assessed by Investigator 3 Months After the Last Metvix PDT or Cryotherapy Cycle | Investigator: Fair | 25 Participants |
| Cryotherapy | Overall Cosmetic Outcome Assessed by Investigator 3 Months After the Last Metvix PDT or Cryotherapy Cycle | Investigator: Excellent | 2 Participants |
| Cryotherapy | Overall Cosmetic Outcome Assessed by Investigator 3 Months After the Last Metvix PDT or Cryotherapy Cycle | Investigator: Good | 23 Participants |
Secondary
Overall Cosmetic Outcome Assessed by Participants 3 Months After the Last Metvix PDT or Cryotherapy Cycle
Cosmetic outcome was assessed by both investigator and participants in participants with 100% of lesions in complete response. Overall cosmetic outcome was assessed with regard to occurrence of the following signs or symptoms; scarring, atrophy, induration, redness or change in pigmentation. The participants graded the cosmetic outcome as: * excellent: no scarring, atrophy or induration, and no or slight occurrence of redness or change in pigmentation compared lo adjacent skin * good: no scarring, atrophy or induration but moderate redness or change in pigmentation compared to adjacent skin * fair: slight to moderate occurrence of scarring, atrophy or induration * poor: extensive occurrence of scarring, atrophy or induration.
Time frame: 3 months after the last metvix PDT or Cryotherapy cycle (Up to 6 months)
Population: Intent-to-treat analysis set included all the participants enrolled in the study who received at least one dose of study treatment. Here overall Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Participants 3 Months After the Last Metvix PDT or Cryotherapy Cycle | Participants: Excellent | 22 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Participants 3 Months After the Last Metvix PDT or Cryotherapy Cycle | Participants: Good | 24 Participants |
| Metvix® PDT | Overall Cosmetic Outcome Assessed by Participants 3 Months After the Last Metvix PDT or Cryotherapy Cycle | Participants: Fair | 0 Participants |
| Cryotherapy | Overall Cosmetic Outcome Assessed by Participants 3 Months After the Last Metvix PDT or Cryotherapy Cycle | Participants: Excellent | 9 Participants |
| Cryotherapy | Overall Cosmetic Outcome Assessed by Participants 3 Months After the Last Metvix PDT or Cryotherapy Cycle | Participants: Good | 24 Participants |
| Cryotherapy | Overall Cosmetic Outcome Assessed by Participants 3 Months After the Last Metvix PDT or Cryotherapy Cycle | Participants: Fair | 11 Participants |
Secondary
Recurrence Rate in Complete Clearance Group
Recurrence rate in complete clearance group was analyzed.
Time frame: 12, 24, 36, 48 and 60 months after last Metvix PDT cycle or Cryotherapy (Up to 5 years)
Population: Intent-to-treat analysis set included all the participants enrolled in the study who received at least one dose of study treatment. Here overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metvix® PDT | Recurrence Rate in Complete Clearance Group | 24 months | 18 lesion |
| Metvix® PDT | Recurrence Rate in Complete Clearance Group | 48 months | 23 lesion |
| Metvix® PDT | Recurrence Rate in Complete Clearance Group | 36 months | 23 lesion |
| Metvix® PDT | Recurrence Rate in Complete Clearance Group | 60 months | 23 lesion |
| Metvix® PDT | Recurrence Rate in Complete Clearance Group | 12 months | 10 lesion |
| Cryotherapy | Recurrence Rate in Complete Clearance Group | 60 months | 19 lesion |
| Cryotherapy | Recurrence Rate in Complete Clearance Group | 12 months | 12 lesion |
| Cryotherapy | Recurrence Rate in Complete Clearance Group | 24 months | 18 lesion |
| Cryotherapy | Recurrence Rate in Complete Clearance Group | 36 months | 18 lesion |
| Cryotherapy | Recurrence Rate in Complete Clearance Group | 48 months | 18 lesion |