Standard treatment for invasive cervical cancer involves either radical surgery or radiotherapy. Childbearing is therefore impossible after either of these treatments. A fertility-sparing option, however, by radical trachelectomy has been shown to be effective, provided that strict criteria for selection are followed. Fertility rates are high, whereas recurrence is low, indicating that a more conservative approach to dealing with early small cervical tumours is feasible. Careful preoperative assessment by magnetic resonance imaging scans allows accurate measurement of the tumour with precise definition to plan surgery. This will ensure an adequate clear margin by wide excision of the tumour excising the cervix by radical vaginal trachelectomy with surrounding para-cervical and upper vaginal tissues. An isthmic cerclage is inserted to provide competence at the level of the internal orifice. A primary vagino-isthmic anastomosis is conducted to restore continuity of the lower genital tract. Subsequent pregnancies require careful monitoring in view of the high risk of spontaneous premature rupture of the membranes. Delivery by classical caesarean section is necessary at the onset of labour or electively before term. Over 1100 such procedures have been carried out vaginally or abdominally, resulting in 240 live births. Radical vaginal trachelectomy with a laparoscopic pelvic-node dissection offers the least morbid and invasive route for surgery, provided that adequate surgical skills have been obtained.
Introduction
Cervical cancer is the second most common malignancy to affect women, with over half a million cases occurring worldwide each year. Of these cases, more than 350,000 will die from their disease because most cases occur in under-developed countries and present at an advanced incurable stage. In Europe, about 38,000 cases are diagnosed each year, more than two-thirds of which would be expected to be cured and survive. Success rates will vary from country to country, depending on the facilities for treatment available and, more importantly, whether a screening programme has been established. Such programmes will detect early stage disease and are aimed at preventing the development of invasive cancer by treating pre-malignant cervical intraepithelial neoplasia before a truly invasive and malignant tumour develops.
Screening by cytology with the use of Papanicolaou cervical smears was first introduced on a population basis in British Columbia in the 1970s. A dramatic decrease in the incidents of cervical cancer and subsequent death rate was reported. These studies were subsequently confirmed with programmes in Scandinavia and then England and Wales. Although opinions differ on what age screening should commence, most authorities agree that as the age of coitarche varies from country to country depending on social and religious principles, the pre-malignant process will have commenced in the most cases by the age of 20 years, and therefore screening should commence at that age.
In developed countries with established screening programmes, the incidence of invasive cancer has continuously decreased, with a proportional increase in the number of early lesions and more particularly an increase in the number of pre-malignant intraepithelial neoplasias. These pre-malignant cases may be successfully treated with excellent results by conisation procedures, usually loop excision with diathermy (the large loop excision of the transformation zone or loop electrosurgical excision procedure).
Cone biopsy remains an integral part of diagnostic and therapeutic management and may be enough of an excisional procedure to treat superficially invasive (micro-invasive) carcinoma. Women with established invasive cancer will be treated either by radiotherapy or radical surgery, depending on stage. These two methods of treatment have withstood the test of time for the past 120 years. Early stage IB tumours have excellent cure rates with radical abdominal hysterectomy and bilateral pelvic-node dissection. This procedure was originally described by Wertheim, although various modifications by either the abdominal or vaginal route (the Schauta operation) have been described, and more recently by the use of laparoscopic and minimally invasive surgery. Cure rates of between 80 and 85% are expected. At the same time, although radiotherapy may offer similar cure rates for early stage disease, it is generally accepted that more advanced stage IIB and above disease should be treated by this method with sensitising chemotherapy usually in the form of weekly cisplatin. Improving cure rates for even more advanced disease have been achieved without the need for surgery. Should recurrence occur, however, then a small number of women may be salvaged by ultra-radical excenterative procedures with or without some form of diversion and reconstruction.
Because of social and professional circumstances, women are delaying childbirth into their mid- and late 30s and even early 40s. As a result, a significant number will present with early invasive cervical cancers having not completed their families or indeed even having started them. There is, therefore, an increasing need for consideration of fertility sparing surgery in suitable cases.
The concept of a vaginal cervicectomy (trachelectomy, from the Greek ‘trachelos’- cervix) was first conceived by Franz Novak in Ljubljana in 1948. In fact, he thought he was treating carcinoma in situ , but a number of invasive cervical cancers were included. Aburel described an abdominal approach for removing the cervix in 1956. Neither of these procedures gained support. In the 1970s, however, Burghardt and Holzer realised that it was not necessary to remove the corpus uteri in all cases of small early invasive cancer.
Uterine conservation was re-introduced by Dargent et al. in the early 1990s. They excised the cervix with para-cervical and upper vaginal tissues from the vaginal route, and at the same time carried out a laparoscopic pelvic-node dissection. Shepherd et al. and Roy and Plant modified this technique and reported that successful outcomes (pregnancy and cure rates) were possible after such surgical treatment. Ungar et al. in 2005 re-introduced the abdominal approach in combination with a pelvic-node dissection, showing that this was feasible, particularly for those surgeons not comfortable with carrying out radical vaginal surgery. Other investigators have supported this.
Imaging techniques, especially with magnetic resonance imaging (MRI), have now been developed for more precise identification and localisation of cervical tumours. Better selection is therefore possible. This allows radical local excision of the cervix and of tumour but with conservation of the corpus uteri and, on occasion, part of the upper proximal cervix at the internal orifice while at the same time obtaining adequate clear margins. As yet, accurate identification of involved lymph nodes, especially with microscopic disease, is not possible. Developments have been made in positron emission tomography and computerised axial tomography. The identification of potential sentinel nodes using radio-nucleotide techniques will also lead to a reduction in the need for routine pelvic-node dissection. This is necessary so that microscopic occult and overt macroscopic lymph-node disease can be identified, and women requiring adjunctive treatment after surgery targeted.
The principles of surgery follow Halstead’s principles to achieve an adequate wide local excision of the primary tumour with surrounding normal para-cervical vaginal tissues. This is for the first or lower part of a Schauta radical vaginal hysterectomy or the lower and distal part of a Wertheim’s radical abdominal hysterectomy with upper partial colpectomy. At the same time, the pelvic lymph nodes draining the cervix are removed either by an extraperitoneal or transabdominal approach, which may be by either laparoscopy or traditional open surgery.
Patient selection
Screening procedures in programmes are becoming increasingly established throughout the world, and many early and small cervical cancers are being detected through abnormal cervical smears. Alternatively, abnormal post-coital or intermenstrual bleeding may result in a clinical examination showing a cervical tumour. Subsequent colposcopy with a biopsy will lead to diagnosis with or without cone biopsy. The extent of the tumour may be assessed clinically with the existence of co-existing intraepithelial neoplasia. Cone biopsy, either by cold knife or diathermy, excision (a large loop excision of the transformation zone or loop electrosurgical excision procedure) is the established method for most accurately assessing the stage and size of a cervical tumour. The depth and diameter of the lesion with a three-dimensional measurement will thus give a volume. For small, superficially invasive tumours, stage IAI and some IAII tumours (i.e. cone biopsy) may be therapeutic and therefore no further treatment is required (see Table 1 for International Federation of Gynecology and Obstetrics staging of early cervical cancer). The margins of excision must be clear of both invasive and high-grade pre-invasive intraepithelial neoplasia. Fertility conservation may therefore be achieved without hysterectomy and without removal of the whole cervix. Although there is a risk of cervical incompetence, depending on how high the excision has been carried and whether the internal orifice has been compromised, a cervical suture may be necessary in any ensuing pregnancy to try and achieve cervical competence and avoid premature labour. Any woman who has had a cone biopsy should report this to her obstetrician during any subsequent pregnancy so that clinical and ultrasound assessment of the cervix may be carried out throughout pregnancy.
| Stage 1 | The carcinoma is strictly confined to the cervix (extension to the corpus should be disregarded). |
| IA | Invasive carcinoma, which may be diagnosed only by microscopy with deepest invasion 5 mm or less and largest extension 7 mm or more. |
| IAI | Measured stromal invasion of 3 mm or less in depth and extension of 7 mm or less. |
| IA2 | Measured stromal invasion of greater than 3 mm and not greater than 5 mm with an extension of not greater than 7 mm. |
| IB | Clinically visible lesions limited to the cervix uteri or pre-clinical cancers greater than stage IA. a |
| IBI | Clinically visible lesion 4 cm or less in greatest dimension. |
| IBII | Clinically visible lesion greater than 4 cm in greatest dimension. |
| Stage II | Cervical carcinoma invades beyond the uterus, but not to the pelvic side wall or to the lower third of the vagina. |
| IIA | Without parametrial invasion. |
| IIAI | Clinically visible lesion 4 cm or less in greatest dimension. |
| IIA2 | Clinically visible lesion greater than 4 cm in greatest dimension. |
| IIB | With obvious parametrial invasion. |
a All macroscopically visible lesions, even with superficial invasion, are allowed to stage IB carcinomas. Invasion is limited to a measured stromal invasion with a maximum depth of 5 mm and a horizontal extension of greater than 7 mm. Depth of invasion should not be greater than 5 mm taken from the base of the epithelium of the original tissue – superficial or glandular. The depth of invasion should always be reported in mm, even in those cases with ‘early (minimal) stromal invasion’ (about 1 mm).
It is generally accepted that skip lesions may occur with glandular intraepithelial neoplasia and involve any crypt or gland throughout the endocervical canal up to the level of the internal orifice. It is now recognised that this may also occur on occasions with squamous cell lesions in crypts that have undergone metaplasia within the transformation zone, although this does not usually extend as far up the endocervical canal as for glandular lesions. Glandular intraepithelial neoplasia, therefore, does require removal of the upper and proximal endocervical canal as well as the ectocervix and transformation zone. It is wise to carry out a fraction of a uterine curettage at the same time as a cone biopsy to be as certain as possible that no other abnormal crypts or glands exist beyond the depth of a conisation procedure.
Given that the incidents of lymph-node involvement with superficially invasive Stage IAI cervical cancer is less than 1% and with IAII superficially invasive cancer generally between 3 and 5%, routine lymph-node dissection may be avoided. If, however, there is extensive lymphovascular space invasion or the lesion is one of the larger sized stage IAII tumours approaching the diameter and depth of invasion of a stage IBI lesion, then it is necessary and wise to carry out a simultaneous pelvic-node dissection with the cone biopsy.
If fertility sparing, however, is not an issue because of the age of the women or she has completed her family, then a hysterectomy is an entirely reasonable option to offer; the radicality and need for pelvic-node dissection will depend on the arguments presented above.
Once the tumour has become a truly invasive stage IB lesion, with a depth of more than 5 mm, the incidence of lymph-node involvement significantly increases. Pelvic-node dissection with a more radical excision of the primary tumour and cervix is then indicated. When fertility preservation is not required, radical hysterectomy should be advised. This will remove the cervix and primary tumour with a surrounding cuff of between 1 and 2 cm of normal tissue, including the para-cervical, para-vaginal and upper vaginal tissues themselves en bloc with the uterus and parametrial tissues. The ovaries and fallopian tubes may be conserved, depending on the age and wishes of the patient. Glandular lesions do have an incidence of about 5 and 10% secondary involvement of the ovaries, which does need to be taken into consideration. A simultaneous en-bloc dissection of the pelvic lymph nodes takes place up to, and including, the common iliac lymph nodes.
Women considering fertility preservation are usually self selected, but will then need to decide after formal assessment and staging whether they should undergo the procedure. Although all women should be advised of current accepted standard methods of treatment, some are not able to take the responsibility before deciding on a more conservative approach, especially when the subsequent potential risks of prematurity are explained. As a general rule, tumours 2 cm or less are suitable for a more conservative approach, such as by trachelectomy, but larger tumours are treated by the more traditional radical hysterectomy or, depending on other circumstances, chemoradiotherapy. All centres, however, carrying out fertility preservation will have individual cases with tumours larger than 2 cm, which after careful assessment have been deemed suitable for a radical wide local excision but with uterine conservation. This, however, is the exception. In our study, three women had stage IIA lesions, six women had lesions larger than 2 cm, and one woman had lesions up to 5 cm in diameter. These are the exceptions and not the rule. In general, the small number of reported cases, however, have occurred in lesions larger than 2 or 3 cm in diameter.
Patient selection
Screening procedures in programmes are becoming increasingly established throughout the world, and many early and small cervical cancers are being detected through abnormal cervical smears. Alternatively, abnormal post-coital or intermenstrual bleeding may result in a clinical examination showing a cervical tumour. Subsequent colposcopy with a biopsy will lead to diagnosis with or without cone biopsy. The extent of the tumour may be assessed clinically with the existence of co-existing intraepithelial neoplasia. Cone biopsy, either by cold knife or diathermy, excision (a large loop excision of the transformation zone or loop electrosurgical excision procedure) is the established method for most accurately assessing the stage and size of a cervical tumour. The depth and diameter of the lesion with a three-dimensional measurement will thus give a volume. For small, superficially invasive tumours, stage IAI and some IAII tumours (i.e. cone biopsy) may be therapeutic and therefore no further treatment is required (see Table 1 for International Federation of Gynecology and Obstetrics staging of early cervical cancer). The margins of excision must be clear of both invasive and high-grade pre-invasive intraepithelial neoplasia. Fertility conservation may therefore be achieved without hysterectomy and without removal of the whole cervix. Although there is a risk of cervical incompetence, depending on how high the excision has been carried and whether the internal orifice has been compromised, a cervical suture may be necessary in any ensuing pregnancy to try and achieve cervical competence and avoid premature labour. Any woman who has had a cone biopsy should report this to her obstetrician during any subsequent pregnancy so that clinical and ultrasound assessment of the cervix may be carried out throughout pregnancy.
| Stage 1 | The carcinoma is strictly confined to the cervix (extension to the corpus should be disregarded). |
| IA | Invasive carcinoma, which may be diagnosed only by microscopy with deepest invasion 5 mm or less and largest extension 7 mm or more. |
| IAI | Measured stromal invasion of 3 mm or less in depth and extension of 7 mm or less. |
| IA2 | Measured stromal invasion of greater than 3 mm and not greater than 5 mm with an extension of not greater than 7 mm. |
| IB | Clinically visible lesions limited to the cervix uteri or pre-clinical cancers greater than stage IA. a |
| IBI | Clinically visible lesion 4 cm or less in greatest dimension. |
| IBII | Clinically visible lesion greater than 4 cm in greatest dimension. |
| Stage II | Cervical carcinoma invades beyond the uterus, but not to the pelvic side wall or to the lower third of the vagina. |
| IIA | Without parametrial invasion. |
| IIAI | Clinically visible lesion 4 cm or less in greatest dimension. |
| IIA2 | Clinically visible lesion greater than 4 cm in greatest dimension. |
| IIB | With obvious parametrial invasion. |
a All macroscopically visible lesions, even with superficial invasion, are allowed to stage IB carcinomas. Invasion is limited to a measured stromal invasion with a maximum depth of 5 mm and a horizontal extension of greater than 7 mm. Depth of invasion should not be greater than 5 mm taken from the base of the epithelium of the original tissue – superficial or glandular. The depth of invasion should always be reported in mm, even in those cases with ‘early (minimal) stromal invasion’ (about 1 mm).
It is generally accepted that skip lesions may occur with glandular intraepithelial neoplasia and involve any crypt or gland throughout the endocervical canal up to the level of the internal orifice. It is now recognised that this may also occur on occasions with squamous cell lesions in crypts that have undergone metaplasia within the transformation zone, although this does not usually extend as far up the endocervical canal as for glandular lesions. Glandular intraepithelial neoplasia, therefore, does require removal of the upper and proximal endocervical canal as well as the ectocervix and transformation zone. It is wise to carry out a fraction of a uterine curettage at the same time as a cone biopsy to be as certain as possible that no other abnormal crypts or glands exist beyond the depth of a conisation procedure.
Given that the incidents of lymph-node involvement with superficially invasive Stage IAI cervical cancer is less than 1% and with IAII superficially invasive cancer generally between 3 and 5%, routine lymph-node dissection may be avoided. If, however, there is extensive lymphovascular space invasion or the lesion is one of the larger sized stage IAII tumours approaching the diameter and depth of invasion of a stage IBI lesion, then it is necessary and wise to carry out a simultaneous pelvic-node dissection with the cone biopsy.
If fertility sparing, however, is not an issue because of the age of the women or she has completed her family, then a hysterectomy is an entirely reasonable option to offer; the radicality and need for pelvic-node dissection will depend on the arguments presented above.
Once the tumour has become a truly invasive stage IB lesion, with a depth of more than 5 mm, the incidence of lymph-node involvement significantly increases. Pelvic-node dissection with a more radical excision of the primary tumour and cervix is then indicated. When fertility preservation is not required, radical hysterectomy should be advised. This will remove the cervix and primary tumour with a surrounding cuff of between 1 and 2 cm of normal tissue, including the para-cervical, para-vaginal and upper vaginal tissues themselves en bloc with the uterus and parametrial tissues. The ovaries and fallopian tubes may be conserved, depending on the age and wishes of the patient. Glandular lesions do have an incidence of about 5 and 10% secondary involvement of the ovaries, which does need to be taken into consideration. A simultaneous en-bloc dissection of the pelvic lymph nodes takes place up to, and including, the common iliac lymph nodes.
Women considering fertility preservation are usually self selected, but will then need to decide after formal assessment and staging whether they should undergo the procedure. Although all women should be advised of current accepted standard methods of treatment, some are not able to take the responsibility before deciding on a more conservative approach, especially when the subsequent potential risks of prematurity are explained. As a general rule, tumours 2 cm or less are suitable for a more conservative approach, such as by trachelectomy, but larger tumours are treated by the more traditional radical hysterectomy or, depending on other circumstances, chemoradiotherapy. All centres, however, carrying out fertility preservation will have individual cases with tumours larger than 2 cm, which after careful assessment have been deemed suitable for a radical wide local excision but with uterine conservation. This, however, is the exception. In our study, three women had stage IIA lesions, six women had lesions larger than 2 cm, and one woman had lesions up to 5 cm in diameter. These are the exceptions and not the rule. In general, the small number of reported cases, however, have occurred in lesions larger than 2 or 3 cm in diameter.
Staging of the tumour
Cervical cancer is most accurately staged by MRI. This will specifically identify and define a cervical tumour and should preferably be carried out before any form of diagnostic cone biopsy. This is not always possible if the conisation is necessary for diagnosis of invasive disease. The MRI will also allow assessment of pelvic lymph nodes, and an abdominal scan (computed tomography or MRI) will allow assessment of the upper retroperitoneal and para-aortic nodes. The size of the tumour may be measured as well as its location and distance from the isthmus ( Figs. 1 and 2 ). The length of the endocervical canal and uterine cavity may be assessed. More accurate measurement is now available using an endovaginal coil with MRI imaging to obtain better definition of the tumour and involvement of the cervix with the inner portion of the paracervical and paravaginal tissues. Axial and sagittal views may be taken and are useful in planning surgery and for reference during the surgical procedure itself.
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