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The term microinvasive cervical cancer identifies this subgroup of small tumors. By definition, these tumors are not visible to the naked eye. Specifically, as seen in Table 30-4, criteria for stage IA tumors limit invasion depth to no greater than 5 mm and lateral spread to no wider than 7 mm. Microinvasive cervical cancer carries a minor risk of lymph node involvement and excellent prognosis following treatment. A retrospective study compared tumors with horizontal spread ≤7 mm and those with >7 mm spread. Higher rates of pelvic lymph node metastasis and recurrence rates were noted as tumor spread further than 7 mm (Takeshima, 1999).
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Stage IA tumors are further divided into IA1 and IA2. These cancers are subdivided to reflect increasing depth and width of invasion and increasing risks for lymph node involvement.
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These microinvasive tumors invade no deeper than 3 mm, spread no wider than 7 mm, and are associated with the lowest risk for lymph node metastasis. Squamous cervical cancers with stromal invasion less than 1 mm have a 1-percent risk of nodal metastasis, and those with 1 to 3 mm of stromal invasion carry a 1.5-percent risk. Of 4098 women studied with this tumor stage, less than 1 percent died of disease following surgery (Ostor, 1995). Because of the low risk of spread into the parametrial or uterosacral nodes, these lesions may be effectively treated with cervical conization alone (Table 30-6) (Keighley, 1968; Kolstad, 1989; Morris, 1993; Ostor, 1994). However, a total extrafascial hysterectomy (type I hysterectomy) is preferred for women who have completed childbearing. Hysterectomy types are described in Table 30-7.
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In stage IA1 microinvasive cancers, the presence of LVSI increases the risk of lymph node metastasis and cancer recurrence to approximately 5 percent. Accordingly, at our institution, these cases are traditionally managed with modified radical hysterectomy (type II hysterectomy) and pelvic lymphadenectomy. Radical trachelectomy with pelvic lymph node dissection can be considered in women desiring fertility preservation (Olawaiye, 2009). This is described on page 670.
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Adenocarcinomas are typically diagnosed at a more advanced stage than squamous cell cervical cancers. Thus, microinvasive adenocarcinomas present a unique management dilemma, due to sparse data regarding this tumor stage. However, based on evaluation of Surveillance Epidemiology and End Result (SEER) data provided by the National Cancer Institute, the incidence of lymph node involvement is similar to that with squamous cancers (Smith, 2002; Spoozak, 2012). Of microinvasive cervical adenocarcinomas, 59 cases managed with uterine preservation and conization have been reported in the literature (Baalbergen, 2011; Bisseling, 2007; Ceballos, 2006; McHale, 2001; Reynolds, 2010; Schorge, 2000; Yahata, 2010). Of these cases, following conization, no recurrences were identified during surveillance in women without LVSI. According to SEER data, the 5-year overall survival for women with stage IA1 adenocarcinoma treated with conization is 98 percent (Spoozak, 2012).
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These microinvasive cervical lesions have 3 to 5 mm of stromal invasion, have a 7-percent risk of lymph node metastasis, and carry a >4-percent risk of disease recurrence. In this group of women, the safety of conservative therapy is yet to be proven. Thus, for this degree of invasion, radical hysterectomy and pelvic lymphadenectomy is recommended.
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For fertility preservation, stage IA2 squamous cervical lesions may be treated with radical trachelectomy and lymphadenectomy. A nonabsorbable cerclage may be placed concurrently with such radical trachelectomy to improve cervical competence during pregnancy. These procedures have high cure rates, and successful pregnancies have been reported. If women are carefully selected for age <45 years, smaller tumor size (<2 cm), and negative nodal involvement, then reported recurrence rates are similar to those of radical hysterectomy (Burnett, 2003; Covens, 1999a,b; Gien, 2010; Olawaiye, 2009). Some experts will offer radical trachelectomy to patients with tumors up to 4 cm (stage IB1). However, prior to surgery, approximately one third of patients with this tumor stage will instead be found to need radical hysterectomy or adjuvant chemoradiation due to intermediate- or high-risk features (Abu-Rustum, 2008; Gien, 2010). Preoperative MR imaging to evaluate the parametria and/or CT scan to evaluate extracervical disease is recommended in these cases. If tumor has extended proximally past the internal cervical os, then trachelectomy is contraindicated. Although this technique is promising, it carries a learning curve, and further studies to validate its efficacy are needed.
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In addition to stage IA1 tumors, some centers are evaluating the safety of conization or extrafascial hysterectomy for a broader group of women with early-stage cervical cancer, since parametrial involvement in microinvasive cervical cancer is rare (Hou, 2011). One study, which included 51 women with stage IA1 to stage IB1 cervical cancer, demonstrated no recurrences at a median surveillance of 21 months for women treated with conization or extrafascial hysterectomy and no nodal dissection (Bouchard-Fortier, 2014). Two women received adjuvant chemoradiation based on specimen histologic analysis results. In addition, SEER data that included 3987 women with microinvasive cervical cancer showed similar survival rates for women with adenocarcinoma treated with conization compared with hysterectomy. However, women with squamous cell carcinoma undergoing hysterectomy had improved survival rates compared with women undergoing conization (Spoozak, 2012).
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Alternatively, patients with microinvasive carcinoma (stages IA1 and IA2) can be treated with intracavitary brachytherapy alone with excellent results (Grigsby, 1991; Hamberger, 1978). Potential candidates for vaginal brachytherapy include women who are elderly or who are not surgical candidates due to comorbid medical disease.
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Women with FIGO stage IA2 through IIA cervical cancer, that is, those without obvious parametrial involvement, may be selected for radical hysterectomy with pelvic lymph node dissection and with or without paraaortic lymph node dissection. Surgery is appropriate for those who are physically able to tolerate an aggressive surgical procedure, those who wish to avoid the long-term effects of radiation therapy, and/or those who have contraindications to pelvic radiotherapy. Typical candidates include young patients who desire ovarian preservation and retention of a functional, nonirradiated vagina.
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Historically, there are five types of hysterectomy, as described by Piver and colleagues (1974). However, hysterectomy techniques used clinically today vary depending on the degree of surrounding tissue that is resected and are categorized as type I, II, or III (see Table 30-7).
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Type I hysterectomy, also known as an extrafascial hysterectomy or simple hysterectomy, removes the uterus and cervix, but does not require excision of the parametrium or paracolpium. It is appropriately selected for benign gynecologic pathology, preinvasive cervical disease, and stage IA1 cervical cancer.
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Type II hysterectomy, also known as modified radical hysterectomy, removes the cervix, proximal vagina, and parametrial and paracervical tissue. This hysterectomy is well suited for tumors in patients with stage IA1 cervical cancer who have positive margins following conization and have insufficient cervix to repeat conization. This hysterectomy is also appropriate for patients with stage IA1 cervical cancer with LVSI. Some institutions perform type II hysterectomies in women with stage IA2 tumors and smaller stage IB tumors with good outcomes (Landoni, 2001).
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Type III hysterectomy, also known as radical hysterectomy, requires greater resection of the parametria. Its goal is to remove microscopic disease that has extended into the parametrium, paracolpium, and around the uterosacral ligaments. To summarize surgical steps, the uterine arteries are ligated at their origin from the internal iliac arteries near the pelvic sidewall, and all tissue medial to this origin, that is, the parametrium, is resected (Fig. 30-11) (Section 46-1). The ureters are completely dissected from their beds and moved laterally for protection during wide excision of the parametrium and paracolpium. The bladder and rectum are mobilized caudally and off the vagina to permit resection of ≥2 cm of proximal vagina. The uterosacral ligaments are clamped at their midpoint. This procedure is performed for stage IA2, stage IB1, stage IIA1, and for some stage IB2 lesions, and for patients with relative contraindications to radiation. These contraindications include diabetes, pelvic inflammatory disease, hypertension, collagen disease, inflammatory bowel disease, or adnexal masses.
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The approach for type I, II, and III hysterectomies can be abdominal, laparoscopic, robot-assisted, or vaginal, depending on patient characteristics and surgeon experience. Advantages of MIS include less blood loss and shorter hospital stay. Intra- and postoperative complications are similar regardless of approach (Ramirez, 2008). Long-term follow-up of patients undergoing laparoscopic radical hysterectomy demonstrates excellent overall survival rates (Lee, 2010).
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Radical Trachelectomy
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This surgical option can preserve fertility in selected young women with cervical cancer, and the cancer stages appropriate for radical trachelectomy mirror those for radical hysterectomy. Compared with radical hysterectomy, radical trachelectomy is less often performed.
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Radical trachelectomy was originally completed vaginally, as described by Dargent (2000), but an abdominal approach is now used more commonly (Abu-Rustum, 2006). The abdominal approach allows for a larger resection of the parametria and is suitable for patients with larger tumors (>2 cm). With radical trachelectomy, steps of radical hysterectomy proceed and thus the uterine vessels are ligated, the parametria is resected, ureterolysis is completed, the bladder and rectum are mobilized, and the upper vagina is resected. To remove the cervix, the uterus is incised at or just below the level of the internal os, with the goal to leave 5 mm of endocervix still attached to the uterus. At this remaining endocervical margin, a thin tissue sample is sharply excised, termed a shave margin, and sent for frozen section. If cancer is absent in this specimen, then reconstruction may proceed. For this, a cerclage using permanent suture is placed, and the knot is tied posteriorly. The uterus is then stitched to the vagina using absorbable sutures. From each side, the corpus ultimately retains blood supply through the uterine branch of the ovarian artery.
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Following radical trachelectomy, women continue to menstruate, and conception can occur naturally. However, cervical stenosis may develop, and thus intrauterine insemination or in vitro fertilization is often needed. Pregnancies are frequently complicated by second-trimester loss and higher rates of preterm birth (Plante, 2005; Shepherd, 2008). In a review of 485 women for whom a radical abdominal trachelectomy was planned, 47 cases (10 percent) were converted to radical hysterectomy. Another 25 women required adjuvant therapy based on final pathologic specimen findings. Thus, 413 women (85 percent) retained fertility. In this fertile cohort, there were 75 pregnancies, 18 miscarriages, 47 deliveries (19 term, 12 preterm, 16 not stated), and 10 women were pregnant at the time of publication (Pareja, 2013). Cesarean delivery with a classical incision is recommended.
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Stage IB lesions are defined as those extending past the limits of microinvasion yet still confined to the cervix. This stage is subcategorized either as IB1 if tumors measure ≤4 cm or as IB2 if they measure >4 cm (Fig. 30-12).
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Stage II cancers extend outside the cervix. They may invade the upper vagina and the parametria but do not reach the pelvic sidewalls. Stage IIA tumors have no parametrial involvement but do extend vaginally as far as the proximal two thirds of the vagina. Stage IIA is further subdivided into stage IIA1 for tumor size ≤4 cm and IIA2 for tumor size >4 cm. Stage IIB cancer may invade the vagina to a similar extent and also invade the parametria.
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Stage IB to IIA cancers do not extend into the parametria and thus can be managed with either surgery or chemoradiation. In a prospective study of primary therapy, 393 women were randomly assigned to undergo radical hysterectomy and pelvic lymphadenectomy or receive primary radiation therapy. Five-year overall survival and disease-free survival rates were statistically equivalent (83 percent and 74 percent, respectively). Patients who underwent radical surgery followed by radiation had the worst morbidity (Landoni, 1997).
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Because chemoradiation and surgery are both viable options, the optimum treatment for each woman ideally assesses clinical factors such as menopausal status, age, concurrent medical illness, tumor histology, and cervical diameter. For stage IB1 and IIA1 cervical cancers, it is left to the physician’s discretion and patient preference as to which treatment modality is preferred. Our general approach to patients with bulky stage IB2 or stage II cervical cancers, that is, those measuring >4 cm, is to manage them primarily with chemoradiation, in a similar fashion to advanced-stage cervical cancers.
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In general, radical hysterectomy for stage IB through IIA tumors is usually selected for premenopausal women who wish to preserve ovarian function and for women who have concerns about altered sexual functioning following radiotherapy. Age and weight are not contraindications to surgery. However, in general, older women may have longer hospital stays, and heavier women can have longer operative time, greater blood loss, and higher rates of wound complications. Surgery is contraindicated in patients with severe cardiac or pulmonary disease.
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In those electing surgery, oophorectomy may be deferred in younger women. One GOG study evaluated tumor spread to the ovary in those with IB tumors electing radical hysterectomy without adnexectomy. Ovarian metastases were identified in only 0.5 percent of 770 women with stage IB squamous cell cancers and in 2 percent of those with adenocarcinomas (Sutton, 1992). For those electing ovarian preservation, ovarian transposition, accomplished by oophoropexy of the ovary into the upper abdomen, can be performed during radical hysterectomy. This repositioning helps preserve ovarian function, in case postoperative pelvic radiation is indicated. In addition, to reduce complications from radiotherapy that might be needed following radical hysterectomy, a surgeon may perform an omental J-flap. Namely, after surgery, the small bowel may become fixed in the pelvis by adhesions, which renders it vulnerable to radiation damage. The omental J-flap can fill the pelvis to reduce this adhesion risk and is described in Section 46-14.
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Systematic lymphadenectomy can lead to complications such as lymphocyst and lymphedema. Therefore, in women with cervical cancer, sentinel lymph node mapping to assess lymphatic spread while avoiding extensive nodal resection is attractive. As a review, the sentinel node is the first node(s) receiving lymphatic drainage from a given tumor. To find this node, either blue dye or a technetium radioactive tracer or both are separately injected preoperatively into the cervix. At surgery, the sentinel node is stained blue and emits radioactivity discernible by Geiger counter. From a metaanalysis including 67 studies, the pooled sentinel node detection rate was 89 percent and sensitivity was 90 percent. Both were highest in women injected with both radiotracer and blue dye. Smaller tumor size (<2 cm) and early-stage diseases were associated with the highest sensitivity and detection rate. At this time, sentinel node for cervical cancer remains experimental (Kadkhodayan, 2015).
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Weighing Surgical and Radiotherapy Complications
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Complications for early-stage cervical cancer radical surgery include ureteral stricture, ureterovaginal fistula, vesicovaginal fistula, bladder dysfunction, constipation, wound breakdown, lymphocyst, and lymphedema. The risk of venous thromboembolism warrants chemoprophylaxis and/or sequential compression devices as outlined in Table 39-8. If radiotherapy is added as an adjuvant to surgery, the risk of many of these is increased.
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On the other hand, radiation therapy also carries long-term complications described in Chapter 28. Of these, altered sexual function secondary to a shortened vagina, dyspareunia, psychological factors, and vaginal stenosis are common. Late urinary and bowel complications such as fistula formation, enteritis, proctitis, and bowel obstruction may also develop following radiotherapy.
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Positive Pelvic Lymph Nodes
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Approximately 15 percent of patients with stage I through IIA cervical cancers will have positive pelvic nodes. Risk factors for lymph node involvement include those listed in Table 30-8. Of those with involved nodes, 50 percent will have grossly positive pelvic nodes intraoperatively. In most cases involving grossly positive nodes, radical hysterectomy is abandoned. After recovering from surgery, whole-pelvic radiation and brachytherapy with concomitant chemotherapy is administered. The 50 percent of patients with involved nodes not grossly identified intraoperatively are considered to be at high risk of recurrence following their radical hysterectomy. As described subsequently, these women require postoperative adjuvant chemoradiation therapy.
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For women who have completed radical surgery for early-stage cervical cancer, the GOG has defined risk factors to help identify women for tumor recurrence. Intermediate risk describes those who on average would have a 30-percent risk of cancer recurrence within 3 years. Factors included in this model are depth of tumor invasion, clinical tumor diameter, and LVSI.
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To determine appropriate treatment, patients with these intermediate-risk factors have been studied. In one trial, women were randomly assigned to receive pelvic radiation therapy following radical hysterectomy or to undergo radical hysterectomy and observation. A nearly 50-percent reduced risk of recurrence was found in those who received postoperative adjuvant radiation therapy (Sedlis, 1999). However, this adjuvant radiation does not prolong overall survival. Notably, these patients did not receive chemoradiation. In our practice, these intermediate-risk patients are counseled regarding their recurrence risk and offered the option of adjuvant chemoradiation therapy. A GOG clinical trial (GOG #263) that is assessing chemoradiation in this patient population is ongoing.
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A high-risk category of early-stage cervical cancer patients who underwent radical surgery has also been described. High-risk is defined as a 50- to 70-percent risk of recurrence within 5 years. These women have positive lymph nodes, positive surgical margins, or microscopically positive parametria (Peters, 2000). This group is routinely offered adjuvant radiation therapy. Moreover, the GOG demonstrated that the addition of concurrent chemotherapy significantly prolongs disease-free and overall survival rates in this group of women with high-risk early-stage cancer (Peters, 2000).
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Adjuvant Hysterectomy Following Primary Radiation
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Treating bulky stage I (IB2) cervical cancers with adjuvant hysterectomy after radiation therapy has been evaluated. Adjuvant hysterectomy reduces locoregional relapse but does not contribute to an overall improvement in survival rates. However, initial lesion size may affect efficacy. In one study, those with tumors measuring <7 cm who underwent postradiation hysterectomy survived longer than did women with equivalent tumors in the radiation-only regimen group. In contrast, those with lesions ≥7 cm who underwent postradiation hysterectomy fared worse than their counterparts receiving only radiotherapy (Keys, 2003).
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Early-stage Cervical Adenocarcinoma
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These cancers may be more radioresistant than squamous cell cervical carcinomas. Although some prefer radical hysterectomy to radiotherapy, studies suggest equivalent survival rates with either (Eifel, 1991, 1995; Hopkins, 1988; Nakano, 1995). However, larger lesions may not regress if managed by radiation alone (Leveque, 1998; Silver, 1998). The centers of bulky tumors may be less radiosensitive due to relative cellular hypoxia. This effect underscores the advantages of radical hysterectomy for women with stage I cervical adenocarcinoma.