Should we modify the current FIGO staging system for early-stage cervical cancer?

Cervical cancer is globally the second most common malignancy in women with almost half a million new cases each year [1]. It is a major cause of morbidity and mortality and because it affects relatively young women, it is an important cause of lost years of life. For many years, the treatment of cervical cancer has focused on aggressive methods, in order to improve survival, without much regard to quality of life.

In recent years, the reduction of morbidity and preservation of reproductive function has been a major concern for women and physicians. The latter has led to the identification of predictive factors of recurrence and favored the development of less aggressive surgery.

The fertility-sparing surgery literature has enabled the identification of prognostic factors and subgroups of patients with different oncological outcome. These data have revealed that the current International Federation of Gynecology and Obstetrics (FIGO) staging system for early-stage cervical cancer may lack accuracy in stratifying patient prognosis. Our aim was to discuss potential areas for revisions of the current FIGO system.

FIGO staging & prognostic factors in early-stage cervical cancer

An accurate staging system is an essential tool, used to provide women with counseling regarding prognosis and to determine eligibility for clinical trial. Currently, the most commonly used staging system for cervical cancer is based on the FIGO staging system (Table 1)[2,3]. The system is based on clinical assessment, including findings from pelvic examination, lesion biopsy, endocervical curettage, radiological studies (lung and bone radiographies, intravenous pyelogram and barium enema) and endoscopic studies (hysteroscopy, cy-stoscopy and sigmoidoscopy) [4].

Factors affecting prognosis in early cervical cancer include tumor volume, depth of stromal invasion, lymphovascular space invasion, parametrial invasion, histological type, resection margins and lymph nodes status. Apart from FIGO stage IA, which requires pathologic examination of the cone specimen to determine size and depth of invasion, the ‘pure clinical’ staging of FIGO IB does not incorporate surgical–pathological features (Box 1).

Discrepancy between surgical & clinical staging for early-stage disease

Although radiation therapy is an equally effective treatment for women with early-stage disease as demonstrated through a randomized trial comparing primary surgery with primary radiotherapy in women with stage IB-IIA cervical cancer, radical hysterectomy is generally considered to be the treatment of choice for young, healthy women, allowing preservation of ovarian function [5]. For example, for a patient with stage IB1 disease, a surgical approach is generally offered in the form of radical hysterectomy, sentinel lymph node biopsy with (or without) bilateral lymph node dissection.

As a consequence, these patients have a surgical–pathological evaluation, which will provide better prognostic information than clinical staging. Compared with surgical staging, FIGO clinical staging has been shown to result in understaging of 20–30% of stage IB patients [6]. Two randomized trials conducted in women with early-stage disease have defined the risks of recurrence based on postoperative pathologic findings and defined the optimal treatment. Women exhibiting at least two risk factors (large tumor size, deep stromal invasion, lymphovascular space invasion) are considered as having an intermediate risk of recurrence. Women exhibiting one of the following risk factors: positive nodes, parametrial invasion, or positive surgical margins, are considered to have a high risk of recurrence [7,8].

Lymph node spread is one of the single most important prognostic factors for survival in early-stage disease, however, as previously mentioned, lymph node status is omitted from the FIGO staging. Lymph node evaluation is an area of research and, recently, results on lymph node evaluation through sentinel node techniques have been reported, with the potential benefits being increased identification of metastatic lymph nodes through ultrastaging and identification of alternate lymphatic drainage sites [9].

Because lymph node metastasis is an important prognostic factor for survival in early-stage disease, future FIGO may include this variable.

Discrepancy between tests recommended by the FIGO & those used in clinical practice

Imaging modalities do not generally provide useful information in women whose operative treatment (radical hysterectomy) is planned. However, they may be useful in pre-operative assessment of those women who are not eligible for radical hysterectomy or are being considered for fertility-sparing surgery. Computerized tomography (CT) or MRI or PET combined with a CT scanner (PET/CT) have also been reported as useful methods for determining the extent of the disease [10]. These methods allow evaluation of the retroperitoneal space, but they do not provide definitive information about the pathologic involvement of the lymph nodes. The pathological lymph node status or suspicious lesion located in the parametrium can be verified by surgical biopsy.

Patterns-of-care studies have demonstrated that the use of the FIGO exams have declined while others, such as CT and MRI, have risen sharply even though they are not included in the FIGO evaluation [11,12]. In the future, CT, MRI and PET/CT techniques and training will continue to develop and it is likely that accuracy for local staging will improve further. There is no doubt that in western countries there will be an increasing discrepancy between the diagnostic tests recommended by the FIGO and those used in daily gynecologic oncology clinical practice in the future.

Subclinical metastasis detected by imaging modalities and confirmed by biopsy may be considered to be included in the staging.

Fertility-sparing surgery has defined a subset of patients having low risk of recurrence

Approximately 50% of women with cervical carcinoma are aged under 40 years old at the time of diagnosis and some of these women may be reluctant to undergo treatments that result in permanent loss of fertility. Cervical cancer tends to spread laterally from the cervix into the parametrial tissue or inferiorly to the upper vagina rather than to the uterus. In small stage IB1, the uterus can generally be spared for future childbearing.

Radical trachelectomy is a curative treatment designed to retain fertility in young women with early-stage cervical cancer. The technique involves removal of the cervix with parametrial tissue and pelvic lymphadenectomy. To date, approximately 500 cases have been reported in the literature with comparable curative rates to radical hysterectomy and more than 50% probability of pregnancy among women who attempted to conceive [13].

The radical trachelectomy literature has allowed the risk of recurrence among these women to be more accurately defined. The most important risk factor in terms of recurrence for these patients is the lesion size. Node-negative women with a tumor of 2 cm or less in size have a very low risk of recurrence, estimated at 2% [13]. Currently, most centers specify a tumor size of 2 cm at the largest diameter as a limiting criterion for conservative uterus-preserving treatments.

In summary, FIGO stage IB1 is strongly diluted and it may be reasonable to stratify FIGO IB1 (less and more than 2 cm) and lymph node status in order to compare results in these women.

Conclusion

Staging systems are intended to facilitate data collection and comparative reporting of end results. The current FIGO staging omits statistically significant variables. There is now a large literature suggesting that surgical–pathologic evaluation improves the accuracy of local staging of early-stage cervical cancer and increasing pressure to move toward a surgical-pathological staging for facilitating comparison between trials. Based on these observations, we suggest that the FIGO definition (1995) of early cervical cancer may be improved by adding more details, including lymph node status and tumor size (less and more than 2 cm), in future classification.

Table 1. FIGO Staging Classification (FIGO 1995, Montreal): cervical carcinoma [2].

Stage	Details
IA1	Invasive carcinoma, confined to cervix, diagnosed only by microscopy. Stromal invasion ≤3 mm in depth and ≤7 mm in horizontal spread
IA2	Invasive carcinoma, confined to cervix, diagnosed only by microscopy. Stromal invasion >3 mm and 5 mm in depth and ≤7 mm in horizontal spread
IB1	Invasive carcinoma, confined to cervix, microscopic lesion >IA2 or clinically visible lesion ≤4 cm in greatest dimension
IB2	Invasive carcinoma, confined to cervix, clinically visible lesion >4 cm in greatest dimension
IIA	Tumor extension beyond cervix to vagina but not to lower third of vagina. No parametrial invasion
IIB	Tumor extension beyond cervix. Parametrial invasion but not to pelvic sidewall and not to lower third of vagina
IIIA	Tumor extension to lower third of vagina but not to pelvic sidewall
IIIB	Tumor extension to pelvic sidewall or causing hydronephrosis or nonfunctioning kidney
IVA	Tumor invasion into bladder or rectum
IVB	Distant metastasis

FIGO: International Federation of Gynecology and Obstetrics.

Box 1. Advantages and disadvantages of current cervical cancer FIGO Staging Classification.

Advantages

• • Can be employed worldwide and is well accepted

• • The definition of different stage groups is simple with characteristics easily recognized in clinical examination

• • Allows comparisons between different institutions

Disadvantages

• • Subclinical metastasis detected by biopsy or surgery are not considered

• • Growing gap between the diagnostic tests recommended by the FIGO and those used in daily practice (CT scanner and/or MRI)

• • Recent randomized trails have include variables (lymph node status, parametrial invasion, margin status, LVSI, deep stromal invasion, lesion size) not recognized by the FIGO system

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Notes

CT: Computerized tomography; FIGO: International Federation of Gynecology and Obstetrics; LVSI: Lymphovascular spaced invasion.