ORIGINAL ARTICLE
Laser. and . cryo surgery for cervical intraepithelial neoplasia A randomized trial with longterm follow-up A. BERGET,’8. AND RE ASS ON^ AND J. E. BOCK^ From the Departments of Obstetrics and Gynecology, Gentofte University Hospital, 2Herlev University Hospital, and Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Acta Obstet Gynecol Scand 1991; 70: 231-235
In a randomized study, 204 patients with exocervical intra-epithelial neoplasia were allocated to either laser evaporation (103) or cryocoagulation (101). The patients were treated on an outpatient basis without anesthesia. In the case of initial treatment failure the same method was to be used for retreatment. One hundred and eighty-seven patients were followed-up for an average of 50 months (12-80). Eighty-six of 94 laser-evaporated patients (91%) and 89 of 93 cryocoagulated patients (96%) were cured after one treatment. Five of 8 laser failures and 3 of 4 cry0 failures were cured by retreatment. The cure rate after one or two laser evaporations was 97% (91 of 94 patients), and after one or two cryo coagulations, 99% (92 of 93 patients). Eighty per cent of residual or recurrent neoplasia occurred within 15 months and 96% within 2 years of treatment. No invasive neoplasia occurred during the follow-up period and no tendency was seen towards higher grades of intra-epithelial neoplasia in the failures compared with the initial diagnoses. It is concluded that laser evaporation and cryocoagulation are equally effective for the treatment of exocervical intra-epithelial neoplasia. Key words: cervical intra-epithelial neoplasia; laser; cryo surgery Submitted December 27, 1W Accepted April 22, 1991
Cervical intra-epithelial neoplasia (CIN) may be treated with either excision or destruction. Excision is performed as a cervical conization with cold knife or laser, while destruction is most often performed as laser evaporation or cryocoagulation. Especially as regards the exocervical CIN, destruction has been recommended because these methods are regarded as minor surgery compared with conization and because their efficacy is comparable to conization (1). Non-randomized trials (1, 2) and randomized trials (3,4, 5 ) with various treatment modalities and criteria suggest that laser and cryodestruction of CIN may be equally successful.
Our first report from the prospective, randomized Copenhagen study (5) dealt in detail with acceptability, complications, side effects, and follow-up possibilities of laser and cryotherapy, and to a lesser extent with the efficacy of the methods. The latter was due to the short period of follow-up. The present report is a comparison of the efficacy of laser evaporation and cryocoagulation based on a long-term follow-up. The question as to which of the techniques is preferable for the treatment of an arearestricted exocervical CIN is discussed on the basis of the results from the first report ( 5 ) and of the long-term efficacy reported here. Acta Obstet Gynecol Scand 70 (1991)
332
A. Berget et al.
'Fable I. Numhcr and age of patients
Diagnosis
Laser therapy Number
Cryotherapy Mean age (range)
Number
Mean age (range)
11
CIN I CIN I1 CIN 111
62 23
29 (21-38) 29 (20-40) 27 (20-33)
61 21
33 (2lLSO) 30 (20-46) 27 (20-33)
-rotai
94
28 (20-40)
93
30 (20-50)
9
Material and Methods A prospective. consecutive, randomized study was
performed at three hospitals affiliated to Copenhagen University. All women with a histologically verified CIN (graded according to Richart (6)) have been evaluated and were enrolled in the study if the following criteria were met: - A fully visible squamocolumnar junction at col-
poscopy : - Extension of the neoplasia no more than 12.5 mm
-
-
-
from the orifice in order to ensure that the cryoprobe used would always cover the neoplasia; No extension of the neoplasia to the vagina; A normal endocervical curettage (ECC); CIN I in portio biopsies at two or more examinations with a 3-6-month interval; CIN I patients should be aged 18+; CIN II in portio biopsies at one examination; CIN I I patients should be aged 18+; CIN 111 in portio biopsies at one examination; extension of the neoplasia into the cervical crypts should not exceed 3 mm; CIN 111 patients should be aged 18-33.
After giving informed consent, those patients fulfilling the criteria were randomized to either laser or cryo treatment. The study was approved by the Medical Ethics Committee. The patients were treated on an outpatient basis without anesthesia-unless other conditions requiring Tahle 11. Length of follow-up after treatment Diagnosis
Laser therapy
Cryotherapy
Months (range)
Months (range)
CIN I CIN I1 CIN 111
49 ( 12-67) 51 (15-74) 48 ( 17-75)
59 (44-66) 51 (16-80) 43 (12-79)
Total
50 ( 12-75)
50 (12-80)
Arru Ohsrn Gytirrol Scaiid 70
(IWI)
anesthesia had to be dealt with at the same time. Per- and postoperative discomfort and hemorrhage. acceptability of the methods and follow-up possibilities have been described earlier (5). The study protocol presupposed a number of at least 100 patients in each treatment group. The reason for the limited number was. that if no difference on a 5% level was demonstrated as regards the primary cure rates, then other conditions than efficacy should decide which method to prefer. As the primary cure rates did not show a statistically significant difference (x? = 0.038. p 0 . 1 ) (5). the enrollment was stopped when a total of 204 patients had entered the study. Of these, 103 were randomized to laser and 101 to cryo treatment. During the enrollment period the total number of patients with CIN was 1,457. Very few patients refused to participate; thus a 14% of the patients with CIN fulfilled the above, rather restricted criteria. Six laser and 2 cryo treated patients have subsequently been excluded from the study because of emigration or refusal to collaborate in the follow-up within one year from treatment. One of the lasertreated patients had persistent CIN at 3 months' follow-up, but declined retreatment and even a check-up. Three laser-treated patients (CIN II) and 6 cryo treated patients (5 CIN I1 and 1 CIN 111) with initial treatment failure did not follow the study protocol with regard to retreatment with the same method as the one initially used. These patients could therefore not be included in that part of the study dealing with the efficacy of the methods. The numbers of patients and their age included in the comparison of laser and cryo efficacy are shown in Table 1. The emigrants, neglectors. and patients not retreated according to the protocol are included in the part of that study dealing with time and grade of residual or recurrent neoplasia. Treatment failure was defined as a histologically verified neoplasia. Follow-up with cytology and colposcopy was scheduled 3+6+6+6 months after treatment and
Laser and cry0 surgery for CIN
233
Table 111. Results of laser and cyro therapy Diagnosis
Method
I1
('IN I C'IN I1 ('IN I l l T0t;Il
Retreatment of failures
Initial treatment
Total cured by laserkryo
Cured
I1
Cured
I?
%I
Laser Cryo
X I0
I I
I 0
Y 10
I00
II
Lascr Cryo
62 61
57 h(I
S I
3 1
h(1
97 1(HI
Lascr Cryo
23 21
21
-7
1
22
96
19
2
21
100
Laser Cryo
Y4
Xh XY
X
4
5 3
YI Y2
97
93
9
7
then once a year. The length of follow-up after last treatmcnt is shown in Table 11. Laser evaporation was pcrformed with a carbon dioxide laser attached to the colposcope, using a focal distance of 300 mm. 15-20 watts, spot size 0.6 nim. the power density being a good SO00 W/cm'. After colposcopic identification of the neoplasia the extent of the area to be evaporated was outlined on the cervix with the laser beam. The evaporation was extended at least 2 mm lateral to the neoplasia and it invariably included the entire transformation zone. Depth of evaporation was 5-7 mm. Cryo coagulation was performed with dinitrogen oxide. using the freeze-thaw-freeze technique for 3+4+3 min - or more if the iceball did not exceed the probe by 4 mm. The cryoprobe used was cone shaped. with a diameter of 25 mm.
Results The initial treatment cured 86 of 94 patients in the laser group (91%) and 89 of 93 patients in the cry0
YI
hl
YY
group (96%) (Table 111). The retreatment with the same method as the one initially used resulted in the cure of 5 of 8 patients in the laser group and 3 of 4 patients in the cry0 group. Altogether, 91 of 94 patients were cured by one or two laser evaporations ( 9 7 u / o ) , and 92 of 93 patients were cured by one or two cryo coagulations (99%). The cure rates do not differ statistically (X2-test). The three laser failures were treated with conization; the patients have been followed-up for 12, 23, and 33 months, respectively. without residual or recurrent neoplasia. The cryo failure occurred 40 months after cryocoagulation for the initial failure; treatment has not yet been performed. As pointed out earlier, three initial laser failure patients and six initial cryo failures did not follow the protocol with regard to retreatment with the same method as the one initially used. These patients were instead retreated with conization of their own volition or on their physician's recommendation; they have been followed-up for 20-48 months without signs of residual or recurrent neoplasia. One patient underwent hysterectomy for uterine
Tiible I V . Time of diagnosis of residual or recurrent neoplasia
Initial diiignosis
Treatment method
Time of diagnosis of residual or recurrent neoplasia (months) -3
CIN I
Laser Cryo
-
('IN I1
Laser Cry0
9 3
('IN 111
Laser Cryo
I 3
liml
Laser Cry0
10
'I
-Y
-15
-2 I
-33
45
40
6
Recurrences after failed retreatment. Acra Ohsrer Gynecol Scand 70 ( I W I )
234
A. Berget et a!.
Tahlc V. Diagnosis of residualhrrent neoplasias
Treatment
1ni tial diagnosis
Method Laser Cryo Laser
CIN I CIN I1
Cry0
Laser
CIN 111
Total "One case in
Residual or recurrent neoplasia CIN I
n
CIN I1
CIN Ill
lnvasive
I 2
II 6
Cryo
3 3
Laser
15
Cry0
I1
each group was a recurrence after failed retreatment.
fibroids 48 months after cryocoagulation; no cervical neoplasia was found on histology. The time of diagnosis of residual or recurrent neoplasia is shown in Table IV. As mentioned earlier, all of the 204 patients are included in this part of the study because later exclusion from the study is irrelevant in this respect. It is seen that two-thirds of residualhecurrent neoplasia had been diagnosed within 9 months and XO'% within 15 months. Ninety-six per cent of failures were diagnosed within 2 years of treatment. After initial treatment. 91% of failures had been diagnosed within 15 months and no recurrence occurred 2 or more years after the initial treatment. After retreatment. there could be a tendency for recurrences to appear somewhat later, but the small number of patients does not allow of any conclusion. The histological diagnoses of residual or recurrent neoplasia are shown in Table V. Here too, all of the 204 patients are included for the same reason as mentioned above. A slight tendency is seen towards lower grades of neoplasia in the residuallrecurrent neoplasias. There was no tendency towards a progression into higher grades in late-detected vis-a-vis early-detected failures. There was no difference between the laser and the cry0 group concerning the distribution of histological grades in the recurrences. No invasive or microinvasive neoplasia occurred.
Discussion The present study has shown that laser evaporation and cryocoagulation of exocervical CIN have such excellent cure rates that both methods can be recommended as routine treatment from the point of view of efficacy. I t is known from our earlier study (5) that both methods are highly acceptable to the patients, even Acru Ohsrrr Gyiirrul Scund 70 (IVY/)
without anesthesia and that the complications with both methods are few and less severe than with conization. But it must be emphasized that in the present study surgery was done by skilled colposcopists and surgeons, and that the inclusion criteria were very strict. These points are necessary preconditions in the evaluation of new technologies; the techniques investigated must be mastered and comparability between methods must be ensured. As the present study has met both of these points, the results are considered reliable. CIN can be treated with great safety with either laser evaporation or cryocoagulation, provided the entire lesion is located on the exocervix as judged by colposcopy, and provided the ECC is negative. and if the lesion has a restricted area as regards the surface spread and crypt involvement. The initial treatment cured 91% of the laser pdtients and 96% of the cry0 patients. Provided that the patients are ready for follow-up, these initial cure rates are satisfactory-especially because retreatment of failures can be done safely with either method, with regard both to cure of the CIN and to the risk of progression into invasion. The histological diagnosis of failure after one or two treatments did not reveal any invasive neoplasia and no tendency was observed towards progression into higher grades of CIN. This might have been due to the fact that 96% o f the failures occurred within 2 years of treatment; perhaps one might also assume that the preoperative grading of the lesions was fairly precise due to the investigators' experience in colposcopy - and hence taking the punch biopsies from areas with the most severe lesions. The success rates after one or two treatments were 97% in the laser group and 99% in the cryo group. This is in agreement with other randomized studies
Laser and cry0 surgery for CIN (3. 4). I t is concluded that laser evaporation and cryocoagulation are equally effective in curing exocervical CIN. In the study protocol we presupposed a total of 100 patients in each treatment group. The reason for this was that if no difference in efficacy were to be seen in groups of that size. then other conditions should determine what method to choose as routine in future. One important condition was the finding from our first study that the follow-up prospects were better after laser than after cry0 treatment. This was due to the greater number of conclusive colposcopies after laser treatment (79'26 versus 50'/0), i.e. colposcopies with a fully visible squamocolumnar junction. A conclusive colposcopy offers the best possibility of taking punch biopsies in the right places in cases of suspicion of residualhecurrent disease. Another aspect in favour of the laser treatment was the observation that patients' discomfort as regards postoperative vaginal discharge was less frequent, of a shorter duration, and seldom malodorous (5). Another important aspect in choosing between laser and cry0 is the fact that laser can be used to carry out excisions (conizations) and combinations of excision and destruction in lesions extending to the vagina. Likewise, the laser can be used with advantage in several other gynaecologic and nongynaecologic fields. For financial reasons the expensive laser apparatus might have to be shared with other hospital departments. The conclusions are that hospital departments are recommended the application of laser technology in
235
the treatment of CIN and that the use of cryocoagulation in private gynaecological practice is safeprovided the gynaecologist is a skilled colposcopist and if its use is limited to area-restricted exocervical CIN.
References I . Berget A. Lenstrup C. Cervical intraepithelial neoplasia. Examination, treatment and follow-up. Obstet Gynecol Survey 1985; 40: 545-52. 2. Ferenczy A. Comparison of cryo- and carbon dioxide laser therapy for cervical intraepithelial neoplasia. Obstet Gynecol 1985; 66: 79-34 3. Jobson VW,Homesley HD. Comparison of cryosurgery and carbon dioxide laser ablation for treatment of cervical intraepithelial neoplasia. Colposcopy Gynecol Laser Surg 1984; I: 173-5. 4. Kwikkel HJ. Helmerhorst RhJM, Bezemer PD. Quaak MJ. Stolk JG. Laser or cryotherapy for cervical intraepithelial neoplasia. Gynecol Oncol 1985; 22: 23-31. 5 . Berget A. Andreasson B, Bock JE, et al. Out-patient treatment of cervical intraepithelial neoplasia; The CO! laser versus cryotherapy, a randomized trial. Acta Obstet Gynaecol Scand 1987; 66: 5 3 1 4 . 6. Richart RM. Cervical intraepithelial neoplasia. Pathol Ann 1973; 8: 301-28. Address for correspondence:
Arne Berget, M.D. Department of Obstetrics and Gynecology Gentofte University Hospital DK-2900 Hellerup Denmark
Laser. and . cryo surgery for cervical intraepithelial neoplasia A randomized trial with longterm follow-up A. BERGET,’8. AND RE ASS ON^ AND J. E. BOCK^ From the Departments of Obstetrics and Gynecology, Gentofte University Hospital, 2Herlev University Hospital, and Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Acta Obstet Gynecol Scand 1991; 70: 231-235
In a randomized study, 204 patients with exocervical intra-epithelial neoplasia were allocated to either laser evaporation (103) or cryocoagulation (101). The patients were treated on an outpatient basis without anesthesia. In the case of initial treatment failure the same method was to be used for retreatment. One hundred and eighty-seven patients were followed-up for an average of 50 months (12-80). Eighty-six of 94 laser-evaporated patients (91%) and 89 of 93 cryocoagulated patients (96%) were cured after one treatment. Five of 8 laser failures and 3 of 4 cry0 failures were cured by retreatment. The cure rate after one or two laser evaporations was 97% (91 of 94 patients), and after one or two cryo coagulations, 99% (92 of 93 patients). Eighty per cent of residual or recurrent neoplasia occurred within 15 months and 96% within 2 years of treatment. No invasive neoplasia occurred during the follow-up period and no tendency was seen towards higher grades of intra-epithelial neoplasia in the failures compared with the initial diagnoses. It is concluded that laser evaporation and cryocoagulation are equally effective for the treatment of exocervical intra-epithelial neoplasia. Key words: cervical intra-epithelial neoplasia; laser; cryo surgery Submitted December 27, 1W Accepted April 22, 1991
Cervical intra-epithelial neoplasia (CIN) may be treated with either excision or destruction. Excision is performed as a cervical conization with cold knife or laser, while destruction is most often performed as laser evaporation or cryocoagulation. Especially as regards the exocervical CIN, destruction has been recommended because these methods are regarded as minor surgery compared with conization and because their efficacy is comparable to conization (1). Non-randomized trials (1, 2) and randomized trials (3,4, 5 ) with various treatment modalities and criteria suggest that laser and cryodestruction of CIN may be equally successful.
Our first report from the prospective, randomized Copenhagen study (5) dealt in detail with acceptability, complications, side effects, and follow-up possibilities of laser and cryotherapy, and to a lesser extent with the efficacy of the methods. The latter was due to the short period of follow-up. The present report is a comparison of the efficacy of laser evaporation and cryocoagulation based on a long-term follow-up. The question as to which of the techniques is preferable for the treatment of an arearestricted exocervical CIN is discussed on the basis of the results from the first report ( 5 ) and of the long-term efficacy reported here. Acta Obstet Gynecol Scand 70 (1991)
332
A. Berget et al.
'Fable I. Numhcr and age of patients
Diagnosis
Laser therapy Number
Cryotherapy Mean age (range)
Number
Mean age (range)
11
CIN I CIN I1 CIN 111
62 23
29 (21-38) 29 (20-40) 27 (20-33)
61 21
33 (2lLSO) 30 (20-46) 27 (20-33)
-rotai
94
28 (20-40)
93
30 (20-50)
9
Material and Methods A prospective. consecutive, randomized study was
performed at three hospitals affiliated to Copenhagen University. All women with a histologically verified CIN (graded according to Richart (6)) have been evaluated and were enrolled in the study if the following criteria were met: - A fully visible squamocolumnar junction at col-
poscopy : - Extension of the neoplasia no more than 12.5 mm
-
-
-
from the orifice in order to ensure that the cryoprobe used would always cover the neoplasia; No extension of the neoplasia to the vagina; A normal endocervical curettage (ECC); CIN I in portio biopsies at two or more examinations with a 3-6-month interval; CIN I patients should be aged 18+; CIN II in portio biopsies at one examination; CIN I I patients should be aged 18+; CIN 111 in portio biopsies at one examination; extension of the neoplasia into the cervical crypts should not exceed 3 mm; CIN 111 patients should be aged 18-33.
After giving informed consent, those patients fulfilling the criteria were randomized to either laser or cryo treatment. The study was approved by the Medical Ethics Committee. The patients were treated on an outpatient basis without anesthesia-unless other conditions requiring Tahle 11. Length of follow-up after treatment Diagnosis
Laser therapy
Cryotherapy
Months (range)
Months (range)
CIN I CIN I1 CIN 111
49 ( 12-67) 51 (15-74) 48 ( 17-75)
59 (44-66) 51 (16-80) 43 (12-79)
Total
50 ( 12-75)
50 (12-80)
Arru Ohsrn Gytirrol Scaiid 70
(IWI)
anesthesia had to be dealt with at the same time. Per- and postoperative discomfort and hemorrhage. acceptability of the methods and follow-up possibilities have been described earlier (5). The study protocol presupposed a number of at least 100 patients in each treatment group. The reason for the limited number was. that if no difference on a 5% level was demonstrated as regards the primary cure rates, then other conditions than efficacy should decide which method to prefer. As the primary cure rates did not show a statistically significant difference (x? = 0.038. p 0 . 1 ) (5). the enrollment was stopped when a total of 204 patients had entered the study. Of these, 103 were randomized to laser and 101 to cryo treatment. During the enrollment period the total number of patients with CIN was 1,457. Very few patients refused to participate; thus a 14% of the patients with CIN fulfilled the above, rather restricted criteria. Six laser and 2 cryo treated patients have subsequently been excluded from the study because of emigration or refusal to collaborate in the follow-up within one year from treatment. One of the lasertreated patients had persistent CIN at 3 months' follow-up, but declined retreatment and even a check-up. Three laser-treated patients (CIN II) and 6 cryo treated patients (5 CIN I1 and 1 CIN 111) with initial treatment failure did not follow the study protocol with regard to retreatment with the same method as the one initially used. These patients could therefore not be included in that part of the study dealing with the efficacy of the methods. The numbers of patients and their age included in the comparison of laser and cryo efficacy are shown in Table 1. The emigrants, neglectors. and patients not retreated according to the protocol are included in the part of that study dealing with time and grade of residual or recurrent neoplasia. Treatment failure was defined as a histologically verified neoplasia. Follow-up with cytology and colposcopy was scheduled 3+6+6+6 months after treatment and
Laser and cry0 surgery for CIN
233
Table 111. Results of laser and cyro therapy Diagnosis
Method
I1
('IN I C'IN I1 ('IN I l l T0t;Il
Retreatment of failures
Initial treatment
Total cured by laserkryo
Cured
I1
Cured
I?
%I
Laser Cryo
X I0
I I
I 0
Y 10
I00
II
Lascr Cryo
62 61
57 h(I
S I
3 1
h(1
97 1(HI
Lascr Cryo
23 21
21
-7
1
22
96
19
2
21
100
Laser Cryo
Y4
Xh XY
X
4
5 3
YI Y2
97
93
9
7
then once a year. The length of follow-up after last treatmcnt is shown in Table 11. Laser evaporation was pcrformed with a carbon dioxide laser attached to the colposcope, using a focal distance of 300 mm. 15-20 watts, spot size 0.6 nim. the power density being a good SO00 W/cm'. After colposcopic identification of the neoplasia the extent of the area to be evaporated was outlined on the cervix with the laser beam. The evaporation was extended at least 2 mm lateral to the neoplasia and it invariably included the entire transformation zone. Depth of evaporation was 5-7 mm. Cryo coagulation was performed with dinitrogen oxide. using the freeze-thaw-freeze technique for 3+4+3 min - or more if the iceball did not exceed the probe by 4 mm. The cryoprobe used was cone shaped. with a diameter of 25 mm.
Results The initial treatment cured 86 of 94 patients in the laser group (91%) and 89 of 93 patients in the cry0
YI
hl
YY
group (96%) (Table 111). The retreatment with the same method as the one initially used resulted in the cure of 5 of 8 patients in the laser group and 3 of 4 patients in the cry0 group. Altogether, 91 of 94 patients were cured by one or two laser evaporations ( 9 7 u / o ) , and 92 of 93 patients were cured by one or two cryo coagulations (99%). The cure rates do not differ statistically (X2-test). The three laser failures were treated with conization; the patients have been followed-up for 12, 23, and 33 months, respectively. without residual or recurrent neoplasia. The cryo failure occurred 40 months after cryocoagulation for the initial failure; treatment has not yet been performed. As pointed out earlier, three initial laser failure patients and six initial cryo failures did not follow the protocol with regard to retreatment with the same method as the one initially used. These patients were instead retreated with conization of their own volition or on their physician's recommendation; they have been followed-up for 20-48 months without signs of residual or recurrent neoplasia. One patient underwent hysterectomy for uterine
Tiible I V . Time of diagnosis of residual or recurrent neoplasia
Initial diiignosis
Treatment method
Time of diagnosis of residual or recurrent neoplasia (months) -3
CIN I
Laser Cryo
-
('IN I1
Laser Cry0
9 3
('IN 111
Laser Cryo
I 3
liml
Laser Cry0
10
'I
-Y
-15
-2 I
-33
45
40
6
Recurrences after failed retreatment. Acra Ohsrer Gynecol Scand 70 ( I W I )
234
A. Berget et a!.
Tahlc V. Diagnosis of residualhrrent neoplasias
Treatment
1ni tial diagnosis
Method Laser Cryo Laser
CIN I CIN I1
Cry0
Laser
CIN 111
Total "One case in
Residual or recurrent neoplasia CIN I
n
CIN I1
CIN Ill
lnvasive
I 2
II 6
Cryo
3 3
Laser
15
Cry0
I1
each group was a recurrence after failed retreatment.
fibroids 48 months after cryocoagulation; no cervical neoplasia was found on histology. The time of diagnosis of residual or recurrent neoplasia is shown in Table IV. As mentioned earlier, all of the 204 patients are included in this part of the study because later exclusion from the study is irrelevant in this respect. It is seen that two-thirds of residualhecurrent neoplasia had been diagnosed within 9 months and XO'% within 15 months. Ninety-six per cent of failures were diagnosed within 2 years of treatment. After initial treatment. 91% of failures had been diagnosed within 15 months and no recurrence occurred 2 or more years after the initial treatment. After retreatment. there could be a tendency for recurrences to appear somewhat later, but the small number of patients does not allow of any conclusion. The histological diagnoses of residual or recurrent neoplasia are shown in Table V. Here too, all of the 204 patients are included for the same reason as mentioned above. A slight tendency is seen towards lower grades of neoplasia in the residuallrecurrent neoplasias. There was no tendency towards a progression into higher grades in late-detected vis-a-vis early-detected failures. There was no difference between the laser and the cry0 group concerning the distribution of histological grades in the recurrences. No invasive or microinvasive neoplasia occurred.
Discussion The present study has shown that laser evaporation and cryocoagulation of exocervical CIN have such excellent cure rates that both methods can be recommended as routine treatment from the point of view of efficacy. I t is known from our earlier study (5) that both methods are highly acceptable to the patients, even Acru Ohsrrr Gyiirrul Scund 70 (IVY/)
without anesthesia and that the complications with both methods are few and less severe than with conization. But it must be emphasized that in the present study surgery was done by skilled colposcopists and surgeons, and that the inclusion criteria were very strict. These points are necessary preconditions in the evaluation of new technologies; the techniques investigated must be mastered and comparability between methods must be ensured. As the present study has met both of these points, the results are considered reliable. CIN can be treated with great safety with either laser evaporation or cryocoagulation, provided the entire lesion is located on the exocervix as judged by colposcopy, and provided the ECC is negative. and if the lesion has a restricted area as regards the surface spread and crypt involvement. The initial treatment cured 91% of the laser pdtients and 96% of the cry0 patients. Provided that the patients are ready for follow-up, these initial cure rates are satisfactory-especially because retreatment of failures can be done safely with either method, with regard both to cure of the CIN and to the risk of progression into invasion. The histological diagnosis of failure after one or two treatments did not reveal any invasive neoplasia and no tendency was observed towards progression into higher grades of CIN. This might have been due to the fact that 96% o f the failures occurred within 2 years of treatment; perhaps one might also assume that the preoperative grading of the lesions was fairly precise due to the investigators' experience in colposcopy - and hence taking the punch biopsies from areas with the most severe lesions. The success rates after one or two treatments were 97% in the laser group and 99% in the cryo group. This is in agreement with other randomized studies
Laser and cry0 surgery for CIN (3. 4). I t is concluded that laser evaporation and cryocoagulation are equally effective in curing exocervical CIN. In the study protocol we presupposed a total of 100 patients in each treatment group. The reason for this was that if no difference in efficacy were to be seen in groups of that size. then other conditions should determine what method to choose as routine in future. One important condition was the finding from our first study that the follow-up prospects were better after laser than after cry0 treatment. This was due to the greater number of conclusive colposcopies after laser treatment (79'26 versus 50'/0), i.e. colposcopies with a fully visible squamocolumnar junction. A conclusive colposcopy offers the best possibility of taking punch biopsies in the right places in cases of suspicion of residualhecurrent disease. Another aspect in favour of the laser treatment was the observation that patients' discomfort as regards postoperative vaginal discharge was less frequent, of a shorter duration, and seldom malodorous (5). Another important aspect in choosing between laser and cry0 is the fact that laser can be used to carry out excisions (conizations) and combinations of excision and destruction in lesions extending to the vagina. Likewise, the laser can be used with advantage in several other gynaecologic and nongynaecologic fields. For financial reasons the expensive laser apparatus might have to be shared with other hospital departments. The conclusions are that hospital departments are recommended the application of laser technology in
235
the treatment of CIN and that the use of cryocoagulation in private gynaecological practice is safeprovided the gynaecologist is a skilled colposcopist and if its use is limited to area-restricted exocervical CIN.
References I . Berget A. Lenstrup C. Cervical intraepithelial neoplasia. Examination, treatment and follow-up. Obstet Gynecol Survey 1985; 40: 545-52. 2. Ferenczy A. Comparison of cryo- and carbon dioxide laser therapy for cervical intraepithelial neoplasia. Obstet Gynecol 1985; 66: 79-34 3. Jobson VW,Homesley HD. Comparison of cryosurgery and carbon dioxide laser ablation for treatment of cervical intraepithelial neoplasia. Colposcopy Gynecol Laser Surg 1984; I: 173-5. 4. Kwikkel HJ. Helmerhorst RhJM, Bezemer PD. Quaak MJ. Stolk JG. Laser or cryotherapy for cervical intraepithelial neoplasia. Gynecol Oncol 1985; 22: 23-31. 5 . Berget A. Andreasson B, Bock JE, et al. Out-patient treatment of cervical intraepithelial neoplasia; The CO! laser versus cryotherapy, a randomized trial. Acta Obstet Gynaecol Scand 1987; 66: 5 3 1 4 . 6. Richart RM. Cervical intraepithelial neoplasia. Pathol Ann 1973; 8: 301-28. Address for correspondence:
Arne Berget, M.D. Department of Obstetrics and Gynecology Gentofte University Hospital DK-2900 Hellerup Denmark
