Follow up after LLETZ: could schedules be modified according to risk of recurrence?

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Abstract

Objectives To document the pattern of recurrence of disease following large loop excision of the transformation zone (LLETZ) to identify a low risk group of women who might benefit from less intensive cytological surveillance.

Design Analysis of prospectively collected information with retrospective review of follow up smears.

Population Three thousand, five hundred and sixty women who underwent LLETZ (median age 31 years; IQR 12 years).

Setting Colposcopy clinic at Northern Gynaecological Oncology Centre, Gateshead.

Methods Women treated with LLETZ from 1988 to 1995 were reviewed. Information on the pathology from LLETZ was collected prospectively and information on the subsequent smears was obtained from the family health authorities.

Results Invasive cancer was detected on the original LLETZ in 134 women who were excluded from the study. Of the remaining 3426 women, histology of LLETZ showed high grade CIN (II and III) in 2371 (69%). At least one follow up smear was undertaken in 3385 women (99%). This constituted 9765 women years of follow up with a mean duration of 35 months. Four hundred and seventeen women (12.2%) had a dyskaryotic follow up smear. Incomplete excision of the lesion and an age of ≥ 50 years at the time of the LLETZ were associated with an increased risk of recurrent CIN. Based on these risk factors the study group was divided into three risk groups: 1. women aged < 50 with no disease at the margins (n=1680); 2. women aged ≥ 50 with disease at the margins (n=93); and 3. women aged < 50 with positive margins, or aged ≥ 50 with negative margins (n=1653). The cumulative survival without recurrent CIN at five years for these groups were 92%, 57% and 86%, respectively.

Conclusion Women aged ≥ 50 with CIN at the margins of excision constituted a small minority high risk group (3%). Consideration should be given to repeat treatment of these women rather than surveillance. Women aged < 50 with complete excision of low grade CIN comprised 51% of the study group. These women were at low risk of recurrent CIN and might benefit from less intensive cytological surveillance following LLETZ.

Introduction

Treatment of women with cervical intraepithelial neoplasia (CIN) reduces the risk of invasive cancer of the cervix by 95%1. Large loop excision of the transformation zone (LLETZ)2 is currently the preferred method of treating CIN both in Britain3 and the United States4. It is associated with a low morbidity5., 6. and has been shown to be as effective in the short term as the older ablative treatments which it has rapidly replaced7., 8., 9., 10., 11.. To date, few studies have addressed the long term results following LLETZ documenting the pattern of recurrence of cytological abnormality beyond a period of six months. Rates of recurrent smear abnormalities of 5% at 24 months12 and 8% at 48 months13 have been described.

LLETZ facilitates accurate histological diagnosis as well as determining the status of the excision margins. This is regarded as a significant advance when compared with older ablative treatments, and there has been an anticipation that this knowledge would result in an inherently more effective treatment12. A recent review, however, has shown no significant difference in the incidence of subsequent cancer when LLETZ was compared with older ablative treatments1 with careful patient selection and good quality colposcopy. Possible explanations for this might include the relatively high incidence of positive margins on LLETZ specimens and the fact that knowledge of the margin status does not influence the subsequent management. Current follow up protocols are based on those older ablative treatments and assume that all women are at equal risk of persistent disease and consequent cancerous change14. The current British National guidelines include a policy of a cervical smear at six months, repeated at 12 months with at least five annual smears before a return to normal screening14. Concern has been expressed that this might represent inadequate follow up for women at high risk1 and excessive surveillance for women at low risk of recurrence.

This aim of this paper was to document the pattern of recurrence of CIN following LLETZ to identify both a low risk group of women who might benefit from less intensive cytological surveillance and a high risk group who might benefit from a more intensive schedule.

Section snippets

Methods

The study involved a review of women with CIN diagnosed by LLETZ from 1988 to 1995. The LLETZ procedures were performed by experienced colposcopists using a standard technique2. Following a colposcopic assessment, the stroma of the cervix outside the transformation zone was infiltrated with local anaesthetic (prilocaine (3%) and vasopressin). A Valleylab Force 2 electrosurgical unit was used, together with an appropriately sized wire loop to excise the transformation zone with the generator set

Results

From 1988 to 1995, LLETZ was performed on 3560 women. Invasive cancer of the cervix was found in 134 women who were excluded from the study. The remaining 3426 women comprised the study group. The age of the women ranged between 16 and 79 years with a median of 31 years (IQR = 12 years). Two hundred and twenty one women (6.5%) were aged ≥ 50 and 173 were aged ≤ 20 years. The remaining 3032 women (88.5%) were between 20 and 50 years of age.

High grade CIN (II and III) was found by LLETZ in 2371

Discussion

It is generally accepted that women who have been treated for CIN have an increased risk of invasive cancer of the cervix1. This is more likely to be explained by the progression of inadequately treated persistent disease than the development of incident CIN. Follow up protocols involving more intensive screening schedules aim to facilitate the early detection of persistent disease. The effectiveness of any such schedule should be balanced against both the psychological impact of more intensive

Conclusion

Recent changes to the National Cervical Screening Programme have had significant results in reducing the incidence of and mortality from cancer of the cervix. The effective treatment of the cervical abnormalities detected is a vital prerequisite to this success. Follow up is extremely important to document the effectiveness of the treatment, but any follow up schedule is not without its negative consequences. Future development of this programme should aim to tailor any increased intervention

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