metastasis correlates with the stage of cervical cancer. In stage IA1 disease (microscopic infiltration of stroma) without vascular space involvement, the probability of pelvic lymph node metastasis is less than 1% (Metcalf et al. 2000) vs. 10–20% in stage IB disease. When there is cancer extension beyond the cervix with involvement of the upper vagina in stage IIA, the risk of pelvic or para-aortic nodal metastases increases to 25% and to over 30% when there is parametrial invasion (stage IIB). The risk is 45% in stage III tumors with involvement of the lower third of the vagina or extension to the pelvic wall and 55% in stage IVA with infiltration of the bladder or rectum. The probability of metastatic spread to para-aortic nodes becomes relevant for stage IIA and above, where it is 8–17%. Para-aortic nodal metastases are regarded as distant metastases and are rare when the pelvic nodes are negative.

Hematogenous dissemination is rare and is seen only in advanced cervical cancer. The 10-year risk of distant metastases varies with the stage and ranges from 3% for IB cervical cancer and 75% for stage IVA. Preferred sites of distant metastases are the para-aortic and supraclavicular lymph nodes, lungs, abdominal cavity, and skeleton (Fagundes et al. 1992).

The probability of tumor recurrence correlates with the disease stage and is 10–20% for stages IB and IIA with negative lymph nodes and 50–70% in advanced tumors of stages IIB–IVA and in patients with nodal metastases (Fig. 3) (Perez et al. 1995). The incidence of pelvic recurrence and metastatic spread is highest during the

first 2 years after diagnosis and primary therapy (Friedlander and Grogan 2002). The true pelvis is the site of recurrent disease in 60–80% of cases (Fagundes et al. 1992; Stehman et al. 1991; Burghardt et al. 1992; Perez et al. 1986).

1.9\ Treatment

Treatment of cervical cancer is individualized to the patient’s disease stage. Although radiation therapy and surgery are equally effective in patients with early-stage disease, younger patients are usually treated surgically in order to preserve the ovaries and avoid radiation-induced complications of the lower genital tract. Chemoradiotherapy is the standard of care for patients with bulky (IB2, IIA2) or locally advanced (IIB–IVA) cervical cancer. Standard concurrent chemoradiation therapy includes external pelvic irradiation plus brachytherapy.

1.9.1\ Treatment of Microinvasive Cervical Cancer

FIGO stage IA1 disease with no lymphovascular invasion has less than a 1% chance of lymphatic metastasis and may be managed conservatively with conization without lymphadenectomy to preserve fertility or with total hysterectomy when preservation of fertility is not desired or relevant. Patients with stage IA2 cervical cancer without lymphovascular invasion can be treated by extrafascial hysterectomy or by conization (to preserve fertility). In the presence of lymphovas-

Fig. 3  Probability of central pelvic recurrence and distant metastasis by tumor stage

25

20

15

10

5

0

Central pelvic recurrence

Distant metastasis

cular invasion, modified radical hysterectomy or radical trachelectomy with pelvic lymphadenectomy should be performed. Radical trachelectomy with laparoscopic lymphadenectomy procedure offers a fertility-sparing option for carefully selected patients with stage IA2 or stage IB1 lesions of 2 cm diameter or less situated at least 1 cm away from internal cervical os. Further criteria for patient eligibility for radical trachelectomy comprise among others the absence of capillary space involvement in intraoperative pathologic specimens and limited endocervical involvement at colposcopic examination (Dargent et al. 2000).

1.9.2\ Treatment of Grossly Invasive Cervical Carcinoma (FIGO IB-IVA)

In patients with stage IB1 and IIA1 cervical carcinoma radical surgery and primary curative radiotherapy have proven to be equally effective. Generally, radical surgery is preferred in younger women because it has less deleterious consequences for the ovaries and vagina and less severe long-term effects on the urinary bladder and rectum as compared with radiotherapy. Radical hysterectomy according to Wertheim (Fig. 4a) and pelvic lymphadenectomy is considered the standard surgical approach to treat stage IB1 and IIA1 cervical cancer (Piver et al. 1974).

Lymph node dissection is performed in all cases of vascular space invasion regardless of depth of infiltration (Piver et al. 1974; Benedet and Anderson 1996; Committee on Practice B-G 2002). Surgical removal and examination of the so-called sentinel lymph node as part of surgical staging are under clinical evaluation. The results available so far suggest a high negative predictive value (Martinez-Palones et al. 2004; Marchiole et al. 2004). The sentinel lymph node is the regional lymph node that is assumed to be the first lymph node affected in case of metastatic spread.

Alternatively to surgery, primary or neoadjuvant radiochemotherapy is used to treat cervical carcinomas with a large volume, with infiltration of the vagina, or with parametrial involvement.

Following surgery, adjuvant radiochemotherapy is performed in patients with an increased risk of local pelvic recurrence. An increased risk of recurrence is assumed when there is a large tumor volume, a positive surgical margin, a very small safety margin, invasion of blood and lymphatic vessels, parametrial infiltration (Plaxe and Saltzstein 1999), or lymph node metastasis. A higher recurrence rate has also been identified for the histologic types of adenocarcinoma and clear cell carcinoma (Sedlis et al. 1999).

Advanced cervical carcinomas (FIGO stages III and IV) and bulky cervical cancers (FIGO IB2 and FIGO IIA2) are not amenable to primary

Fig. 4  Operative techniques. (a) Radical hysterectomy with removal of the uterus, vaginal cuff, parametria, and parailiac and para-aortic lymph nodes. Depending on the extent of parametrial removal, different types of hysterectomy are distinguished according to Piver. (b) Radical

trachelectomy with removal of the uterine cervix, parametria, a vaginal cuff, and parailiac lymph nodes with subsequent uterovaginal anastomosis (from the lecture script of the Dept. of Gynecology and Obstetrics, Jena University Hospital, Germany)