66_00e general management

General Management

Controversy continues between those who advocate radical surgery (58,380,478) and those who favor RT for the treatment of carcinoma of the uterine cervix. Russell et al. (534) noted that the of use of radiation as the sole therapy or as a component of the course of therapy has declined, coincident with a 32.3% increase in the use of hysterectomy alone and a 33.7% reduction in the use of radiation alone. A rise in the use of chemoradiation in patients with advanced stages was described by Eifel et al. (143) in a Patterns of Care record review (from 19% in 1996 to 63% in 1999). Moreover Barbera et al. (27) also reported a significant increase in the use of chemoradiation in Canada after the U.S. National Cancer Institute Bulletin on the subject (436).
The decline in use of irradiation may be related to earlier tumor detection in recent times because of greater awareness by physicians and patients, the widespread use of Pap smear screening, and the increased number of gynecologic oncologists, with a greater use of surgery in the treatment of patients with earlier cancer stages. Kapp and Giacca (295) offered new directions in radiation biology that potentially could have applications in the future treatment of patients with carcinoma of the cervix.

Patients should be treated with close collaboration between the gynecologic oncologist and the radiation oncologist, and an integrated team approach should be vigorously pursued. It is critical that the results of surgical series be reported based on the initial clinical staging, including all patients evaluated for that therapeutic modality, to make more meaningful comparisons with radiation therapy outcomes.

Carcinoma In Situ

Patients with carcinoma in situ, which may include those with severe dysplasia, are usually treated with a total abdominal hysterectomy with or without a small vaginal cuff. The decision to remove the ovaries depends on the age of the patient and status of the ovaries.
Occasionally, when the patient wishes to have more children, carcinoma in situ may be treated conservatively with a therapeutic conization (39), laser therapy, or cryotherapy (505). This approach should be judiciously selected when the extent of tumor allows it and the patient is reliable for continued follow-up (84). Conization microscopic margins are critical in decision making regarding a conservative approach or proceeding with a hysterectomy. A therapeutic hysterectomy can be performed 6 weeks after the conization.

Irradiation may be useful for the treatment of carcinoma in situ, particularly in patients with strong medical contraindications to surgery or when there is extension of the lesion to the vaginal wall or multifocal carcinoma in situ in both the cervix and the vagina (113,478).

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In a group of 26 patients with carcinoma in situ treated at Washington University with intracavitary brachytherapy alone (approximately 5,000 mgh, 45 Gy to point A with LDR) with tandem and ovoids, no recurrences were recorded (201). Ogino et al. (449) used HDR brachytherapy in 14 patients with grade 3 cervical and six with grade 3 vaginal intraepithelial neoplasia (three with microinvasion) and six with recurrent cervical intraepithelial neoplasia after hysterectomy. Seventeen patients were treated with HDR brachytherapy alone, and three in combination with EBRT without surgery. The mean dose of HDR brachytherapy was 26.1 Gy (range, 20 to 30 Gy) prescribed at point A for intact uterus, or at 1 cm superior to the vaginal apex or 1 cm beyond vaginal mucosa for lesions of the vaginal stump. Fourteen patients were alive and six had died from intercurrent disease; none had recurrent disease. Rectal bleeding occurred in three patients and subsided spontaneously. Moderate and severe vaginal reactions were noted in two patients in whom the treatment included the entire vagina.

Stage IA

The definition of microinvasive (stage IA) carcinoma of the cervix lacks uniform diagnostic criteria; tumor volume in the stroma may be a more reliable criterion than depth of invasion to arrive at a definition of stage IA. Depth of invasion and tumor confluence have been identified as prognostic factors that should be taken into consideration in the planning of therapy (35). Conization is mandatory for more accurate diagnosis. According to Kolstad (333), lesions <1 mm in depth can be treated with conization, provided all margins are tumor free and continued careful follow-up is instituted. Raspagliesi et al. (506) used margins of 8 to 10 mm as guidelines for clearance in conization. Smaller margins or lymphovascular invasion in addition to depth of invasion were prognostic factors for recurrence.

Early invasive carcinoma of the cervix (stage IA2) is usually treated with a total abdominal or modified radical hysterectomy, but it can be treated with intracavitary radioactive sources alone (6,500 to 8,000 mgh, 60 to 75 Gy to point A, in two LDR insertions, respectively). With HDR brachytherapy the dose is approximately 36 to 45 Gy in 6 to 8 fractions, depending on tumor volume and depth of stromal invasion.

When the depth of penetration of the stroma by tumor is <3 mm, the incidence of lymph node metastasis is 1% or less, and a lymph node dissection or pelvic external irradiation is not warranted (201,478). With more extensive lesions, a Wertheim radical hysterectomy with pelvic lymphadenectomy is the preferred treatment. Tumor control with all treatment methods is over 95%, with patients eventually dying of intercurrent disease. Gadducci et al. (171) treated 30 patients with conization, 82 with total and 54 with radical hysterectomy; the recurrence rate was 10%, 4.9%, and 9.3%, respectively. None of 67 patients submitted to lymphadenectomy had positive pelvic nodes. In 98 patients with adenocarcinoma of the cervix none of 48 with depth of invasion (DOI) ≤5 mm had involved parametria or positive nodes, in contrast to 6/36 (16%) with DOI >5 mm (26).

Recently, in selected institutions, vaginal trachelectomy (removal of the cervix) and laparoscopic lymphadenectomy have been used to treat young patients with microinvasive carcinoma. The number of patients is small and follow-up is short, but preliminary results show a low incidence of recurrences (505).

Stages IB and IIA

The choice of definitive irradiation or radical surgery for stage IB and IIA carcinoma of the cervix remains controversial, and the preference for one procedure over the other depends on the institution, the gynecologic oncologist or radiation oncologist involved, the general condition of the patient, and characteristics of the lesion. An operation has been preferred by some in young women to preserve the ovaries and the possibility of a more pliable vagina and better sexual activity after surgery. However, in some reports (18), ovarian function preservation has been observed in only 50% to 60% of surgically treated patients not receiving irradiation.
Another important alleged advantage of surgery is the opportunity to do a thorough pelvic and abdominal evaluation. However, surgical staging has not been shown to improve overall patient survival (437,651). Kupets et al. (343) assessed the value of debulking large nodes and concluded that the incremental overall benefit by stage was small. Exploratory laparotomy eliminates from the surgical group patients with more advanced disease. Delgado et al. (117) described a GOG study in which 1,125 patients were registered before surgery; 80 were ineligible after strict pathology review, an additional 129 patients were explored, but the hysterectomy was abandoned because of intraoperative complications in 49 patients or extent of disease beyond the uterus in 80 patients. Failure to account for these patients in other series overestimates the efficacy of radical surgery.

Few randomized trials have compared the results of radical hysterectomy with definitive RT. This subject is discussed further in the Results of Therapy section of this chapter.

Despite a slower regression after irradiation, reflecting cellular kinetics and a slow growth, no difference in tumor control or survival has been observed in adenocarcinomas compared with epidermoid carcinomas (200), although prognosis is related to tumor volume (141). Because of the predilection for endocervical involvement in adenocarcinoma, a combination of irradiation and conservative hysterectomy has been advocated by some authors (536), although results are comparable with those obtained with irradiation alone (200).

Bulky endocervical tumors and the so-called barrel-shaped cervix have a higher incidence of central recurrence, pelvic and para-aortic lymph node metastasis, and distant dissemination (160). Because of the inability of intracavitary sources to encompass the entire tumor in a high-dose volume, larger doses of external radiation to the whole pelvis or extrafascial hysterectomy, or both, have been advocated to improve therapeutic results (262). An extrafascial conservative hysterectomy has been recommended 6 weeks after completion of higher dose preoperative irradiation (20 Gy to the whole pelvis, additional 30 Gy to the parametria with midline shielding, and one intracavitary LDR insertion for 5,500 mgh, delivering approximately 50 Gy to point A, with a total dose to point A of 70 Gy). Higher doses of irradiation alone yield equivalent pelvic tumor control and survival rates (144,478). This subject is discussed further later in this chapter.

Stages IIB, III, and IVA

Patients with stage IIB and III tumors are treated with irradiation, usually combined with chemotherapy. Patients with stage IVA disease (bladder or rectal invasion) can be treated either with higher doses of external radiation to the whole pelvis, intracavitary insertions (total dose to point A with LDR brachytherapy about 90 Gy), and additional parametrial irradiation, or with pelvic exenteration (112), usually combined with chemotherapy. Niibe et al. (443), in analysis of 179 patients with stage IIIB adenocarcinoma, suggested that an optimal dose for these tumors was T-BED >10 or 100 Gy.

Numerous reports have been published on the concomitant use of irradiation and cytotoxic agents (hydroxyurea, cisplatin, and 5-fluorouracil [5FU], in some trials combined with mitomycin C) administered to obtain a radiosensitizing effect (83,98,459). Several publications show that chemotherapy combined with irradiation alone or after radical hysterectomy has value in the treatment of locally extensive squamous-cell carcinoma of the cervix, as it will be discussed in more detail later in this chapter.

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Small-Cell Carcinoma of the Cervix

Small-cell carcinoma of the cervix, like its counterparts in the lung and other anatomic locations, has a high proliferation rate and marked propensity for regional lymph node and distant metastases. Miller et al. (410) demonstrated that all small-cell carcinomas of the cervix are aneuploid, compared with only 30% of large-cell nonkeratinizing squamous carcinomas. The incidence of lymphatic vascular space invasion is 80% to 90% (2), and lymph node metastases has been reported to be 40% to 67% (551). These patients must be evaluated in conjunction with a medical oncologist; the work-up should include bone marrow aspiration biopsy of the iliac crest and other tests to rule out metastatic spread. Furthermore, the basic therapy should include a combination of cytotoxic agents with pelvic EBRT and intracavitary brachytherapy to doses similar to those used in squamous-cell carcinoma, although some patients have been treated with radical surgery. As in carcinoma of the lung, it is probably more efficacious to administer two or three cycles of chemotherapy before the initiation of radiation therapy, if there is no acute bleeding. If bleeding is present, prompt institution of radiation therapy is necessary.
At Washington University, patients with small-cell carcinoma of the cervix are treated with the same irradiation techniques as outlined for other histologic varieties of cervical carcinoma in combination with multiagent chemotherapy. The most frequently prescribed drugs are cyclophosphamide (1,000 mg/m2), doxorubicin (50 mg/m2), and vincristine (1 mg/m2) given every 3 or 4 weeks. Etoposide (VP-16) is being incorporated more frequently into some of the regimens (424). Depending on age and tolerance to therapy, the doses of radiation may be decreased by approximately 10%.

Hoskins et al. (261) used a multimodality regimen of four cycles of cisplatin and etoposide with concurrent locoregional RT in 11 women with small-cell carcinoma of the cervix. Prophylactic cranial irradiation was used in all patients except those with primary tumor progression. The 3-year overall and failure-free survival rates were 28%. Four patients were alive in first remission; the remaining seven died (two from toxicity, five from cancer). Toxicity of therapy was significant, with 70% experiencing severe neutropenia; 40% were admitted to the hospital for emesis control.

Twelve patients with small-cell carcinoma of the cervix were treated with radical hysterectomy (five received postoperative RT for lymph node metastases and two for close margins). With a mean follow-up of 73 months, the disease-free survival rate was 36.4% compared with 71.6% for patients with non–small-cell carcinoma (551). Four of five patients who received postoperative irradiation died with pelvic recurrence and three also had disseminated metastases. However, only those with small lesions or those who received adjuvant irradiation were cured.

Delaloge et al. (114) reported only two of 10 patients with neuroendocrine small-cell carcinoma of the cervix surviving at 13 and 53 months after treatment, which included surgery, irradiation, and cisplatin/etoposide combination chemo-therapy.

Boruta et al. (49) reviewed results in 11 of their own and 23 other patients with early stage neuroendocrine cervical carcinoma identified by a Medline search. Lymphovascular space invasion was present in 21/27 (78%) patients (seven unknown) and 15/29 (52%) had lymph node metastases. Fifteen patients were treated with platinum/etoposide (PE), seven with vincristine/doxorubicin/cyclophosphamide (VAC), two with alternating cycles of VAC and PE, and 10 with other chemotherapy regimens. Twenty women were treated with radiation therapy. The presence of lymph node metastases was a poor prognostic factor (p <0.001). PE and VAC chemotherapy was associated with increased survival (p <0.01).

Combination of Irradiation and Surgery
Preoperative Irradiation

At some institutions, the combination of preoperative irradiation and radical hysterectomy has been used in the treatment of patients with bulky stage IB and IIA tumors. Sometimes a LDR intracavitary insertion alone before surgery has been used (5,000 to 6,000 mgh). The rationale for use of an operation has been the alleged inability of irradiation to eradicate completely the metastatic tumor in the pelvic lymph nodes (478).

Postoperative Radiation Therapy after Radical Hysterectomy

Patients who have undergone radical hysterectomy with no preoperative radiation therapy at Washington University are considered for postoperative radiation therapy if they have high-risk prognostic factors, which include two or more positive pelvic lymph nodes, or patients with negative nodes who have microscopic positive or close (<3 mm) margins of resection, deep stromal invasion, or vascular/lymphatic permeation. These patients have intermediate risk of failure (117).

In a study of Alvarez et al. (12), high-risk and intermediate-risk patients had 56% survival, and low-risk patients a 92% survival. It is possible that negative-node patients with multiple intermediate risk factors may be at greater risk than patients with a single positive node (608). More than one-third of patients who have recurrences will present with extrapelvic disease (354). A randomized trial showed that postoperative pelvic irradiation alone (527) or combined with cisplatin and 5FU improve outcome in these patients (483).

In patients receiving postoperative irradiation, extreme care should be exercised in designing treatment techniques, including intracavitary insertions; because of the surgical extirpation of the uterus, the bladder and rectosigmoid may be closer to the radioactive sources than in the patient with an intact uterus. Furthermore, vascular supply may be affected by the surgical procedure, and adhesions can prevent mobilization of the small bowel loops that may be fixed in the pelvis.

Van den Berg et al. (628), in a project based on 47 lymphangiograms and 15 CT scans, asked radiation oncologists (n = 17) to define the clinical target volume (CTV) and planning target volume (PTV), and to delineate on simulation films the RT treatment portals to be used after a radical hysterectomy with lymph node dissection for stage IB or IIA cervical carcinoma with positive iliac lymph nodes. Large variations were observed in the portals used and in treatment techniques. From the digitized films, it appeared that in 50% of the cases the defined PTV was not covered adequately. Furthermore, 71% of the treatment plans would not cover the lateral borders of the reference PTV sufficiently. Thus, there is a need for a consensus in the design of standardized treatment volumes in these patients, particularly if IMRT will be used.

When metastatic pelvic lymph nodes are present, treatment has consisted of 50 Gy to the whole pelvis delivered with a four-field technique. Patients with positive common iliac or para-aortic node metastases should receive 50 Gy to the para-aortic region as well with extended fields. IMRT is particularly suited to treat these patients (150).

In patients not irradiated before surgery, for whom postoperative irradiation is indicated for deep stromal invasion in the cervix or close or positive surgical margins, an alternative is to deliver pelvic external irradiation (20 to 30 Gy to the whole pelvis and additional dose with a small midline block to complete 50 Gy to the parametria) in combination with an LDR intracavitary insertion for 65 Gy to the vaginal mucosa (approximately 1,800 mgh) or 30 to 36 Gy with HDR brachytherapy in five to six fractions, using colpostats or a cylinder (Fig. 66.6). At

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some institutions, external irradiation alone (50 Gy to the midplane of the pelvis) with a four field box technique has been used. Hong et al. (255) recommended, for node-negative patients with high risk factors, to irradiate only the low pelvis (median dose 50 Gy), which resulted in a reduction of grade 3 small bowel morbidity (3/149 = 2%) in comparison with patients treated to the whole pelvis (6/79 = 8%). Five-year disease-specific survival was 84% and 86%, respectively.

Because of the disruption of the anatomy due to parametrial and vaginal cuff resection, which would place potential foci

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of parametrial tumor at a distance from the vaginal ovoids, it has been recommended that postoperative vaginal intracavitary brachytherapy alone be used only for patients with carcinoma in situ (or with minimal invasive carcinoma, in our opinion) at the vaginal margin of resection (478).

Carcinoma of the Cervix Inadvertently Treated with a Simple Hysterectomy

Occasionally, a simple or total abdominal hysterectomy is performed, and invasive carcinoma of the cervix is incidentally found in the surgical specimen. In general, extrafascial abdominal hysterectomy is not curative because the paravaginal or paracervical soft tissues and vaginal cuff are not removed. Furthermore, it may be technically difficult to perform an adequate radical operation after previous simple hysterectomy (14). If only microinvasive carcinoma is found when a total or extrafascial hysterectomy with a wide cuff is performed, no additional therapy is necessary; for lesions with deeper stromal invasion, at most, one or two vaginal intracavitary insertion(s) to deliver a 65-Gy LDR mucosal dose (or 36 Gy at 0.5 cm in five or six fractions with HDR brachytherapy) to the vault is sufficient. If a less comprehensive resection was carried out, it is critical that these patients receive radiation therapy immediately when their postoperative status allows it, because the prognosis is worse if postoperative irradiation is not administered.
In patients with fully invasive tumor, therapy consists of 20 to 40 Gy to the whole pelvis and additional parametrial dose to complete 50 Gy combined with one or two LDR intracavitary insertion(s) to the vaginal vault for a 40 to 65 Gy (or equivalent HDR) mucosal dose (depending on whole pelvis dose). If there is gross tumor present in the vaginal vault or parametrium, the dose to the whole pelvis should be 40 Gy with an additional parametrial dose of 10 to 20 Gy. An intracavitary insertion as outlined previously should be performed. If there is residual tumor, an interstitial implant should be carried out to selectively increase the dose to this volume. Specific treatment recommendations are summarized in Table 66.7.

Andras et al. (19) reported on 148 patients, 90 of whom were available for 10-year evaluation, and dividing them in five groups depending on tumor extent when therapy was instituted. The majority of patients were treated with 50-Gy total-pelvis irradiation (with 10-Gy parametrial boost through reduced fields), at times combined with vaginal vault intracavitary irradiation. Eight major complications were noted in 148 patients.

Ampil et al. (14) described results in 44 patients receiving postoperative irradiation after hysterectomy for stage IB and IIA carcinoma of the uterine cervix (15 patients treated with radical hysterectomy). Their 5-year results were 88% and 83% local tumor control and 69% and 67%, respectively. In three patients treated with intracavitary vaginal cuff irradiation only, two had tumor control.

Green and Morse (190) reported 9/30 patients (30%) surviving 5 years after definitive radiation therapy for treatment of invasive cervical carcinoma after simple hysterectomy. The same authors noted that 14/32 patients retreated with another surgical procedure, usually a Wertheim hysterectomy, died within 5 years. They pointed out that the 5-year cure rate was 30% in patients treated within 1 year after the hysterectomy but was only 16% in those treated after 1 year. Thus, the time at which the patient is treated and the volume of tumor are important prognostic factors.

Crane and Schneider (99) described results in 18 patients treated with RT (with or without brachytherapy) for invasive carcinoma of the cervix discovered after simple hysterectomy. The 10-year actuarial local tumor control was 88%, and the overall survival rate 93%. Huerta et al. (267), in 59 patients with carcinoma of the cervix incidentally found in simple hysterectomy specimens (27 with gross residual tumor) who were treated with postoperative RT, reported a 3-year survival of 59%; factors affecting prognosis included gross residual tumor, time between hysterectomy and irradiation longer than 6 months, RT doses lower than 50 Gy, and histological tumor type.

Munstedt et al. (428) reported on 119 patients who received postoperative RT after radical hysterectomy and 80 after simple hysterectomy. There was a trend toward better survival in the radical hysterectomy group, but the authors concluded that postoperative RT is a good treatment in patients with invasive cervical cancer who undergo a simple hysterectomy. In another report of 105 patients with invasive cervical carcinoma found in inadequate surgery specimens treated with postoperative RT, 5-year pelvic tumor control was 72% and survival rate 55%. Late rectal toxicity was 19%, bladder 4.8%, and small bowel 14.3% (539) (Table 66.8).

Surgical Techniques

Several types of hysterectomy are used in the management of carcinoma of the uterine cervix (490) (Table 66.9).

Total (extrafascial) abdominal hysterectomy (class I) consists of removal of the cervix and adjacent tissues as well as a small cuff of the upper vagina in a plane outside the pubocervical fascia. There is minimal disturbance of the ureters and the trigone of the bladder.

In modified radical extended hysterectomy (class II), the cervix and upper vagina are removed, including paracervical tissues, and the ureters are dissected in the paracervical tunnel to their point of entry into the bladder. Because the ureters are unsheathed and retracted laterally, parametrial and paracervical tissue can be safely removed medial to the ureter. This operation may be performed with or without lymphadenectomy.

Radical abdominal hysterectomy (class III) with bilateral pelvic lymphadenectomy consists of a wider resection of the parametrial tissues to the pelvic wall, with dissection of the ureters and mobilization of the bladder as well as the rectum to allow for more extensive removal of tissues. Also, a vaginal cuff of at least 2 to 3 cm is always included in the procedure. A bilateral pelvic lymphadenectomy is usually carried out. This operation is often referred to as the Wertheim or Meigs procedure. More extensive radical hysterectomies (class IV and V) have been described, but they are rarely performed.

Pelvic exenteration has been used for en masse removal of the pelvic viscera for stage IVA and recurrent carcinoma of the cervix. This operation, which is not done as a palliative procedure, consists of a radical hysterectomy, pelvic lymph node dissection, removal of the bladder (anterior exenteration), removal of the rectosigmoid colon (posterior exenteration), or both (total exenteration). The ileum or sigmoid has been the usual means of achieving urinary diversion. Because some patients have a pelvic recurrence after radiation therapy, the transverse colon is used for the urinary conduit. Proof that there is no fixation to the pelvic wall and no extension of disease beyond the pelvis is mandatory. Metastases outside the pelvis, including those in para-aortic lymph nodes or any viscera, are absolute contraindications to the procedure. Bilateral ureteral obstruction secondary to tumor is also a relative contraindication (630). Patients with sacroiliac or hip pain or leg edema rarely benefit from this procedure and should be excluded on a clinical basis. In former years, pelvic exenteration was used in stage IVA carcinoma of the cervix with extension to the bladder. Modern radiation therapy has made this a rare indication for exenteration (337,412,625).

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Pretreatment Laparotomy and Nodal Staging

Pretreatment extraperitoneal staging of patients with bulky or locally advanced cervical carcinoma may afford debulking of macroscopically positive lymph nodes without significantly increasing treatment-related morbidity and mortality. After extraperitoneal lymph node dissection, the use of high-energy photon beams and limiting the tumor dose to extended volumes in the para-aortic region to 50 Gy decreases the probability of complications (478). IMRT also enhances the sparing of adjacent abdominal normal tissues (150,493).

Cosin et al. (97) reviewed 266 patients with locally advanced cervical carcinoma who underwent extraperitoneal pelvic and para-aortic lymphadenectomy before RT. Patients were divided into four groups: group A had negative lymph nodes; B, resected, microscopic lymph node metastases; C, macroscopically positive lymph nodes that were resectable at the time of surgery; and D, unresectable lymph nodes. Lymph node metastases were detected in 50% of patients. All patients received EBRT and brachytherapy; patients with lymph node metastases received extended-field irradiation. Five- and 10-year disease-free survival rates were similar for all patients in groups B and C. All patients in group D recurred. There was a 10.5% incidence of severe radiation-related morbidity and a 1.1% incidence of treatment-related deaths.

Exploratory laparotomy and nodal staging to evaluate the presence of metastases to the pelvic or para-aortic nodes has had no demonstrated impact on survival (Table 66.10). A higher incidence of complications has been described when extensive transperitoneal para-aortic lymph node dissection is carried out (Table 66.11) and patients are later treated with definitive RT (11.5% incidence of major complications with transperitoneal compared with 3.9% in the extraperitoneal lymphadenectomy group) (p = 0.03) (645).

Wharton et al. (651) reported on 120 patients with squamous carcinoma of the uterine cervix who had preirradiation celiotomy; 64 had metastasis to the lymph nodes (33% in the pelvis and 20% in the common iliac or para-aortic lymph nodes). There were 16 fatal complications, and 32 had major intestinal complications. Most patients with positive lymph nodes died with distant metastasis. Because of this negative experience, preirradiation laparotomy was discontinued at the M.D. Anderson Cancer Center, and the status of the lymph nodes was investigated with lymphangiography and verified when possible with percutaneous transabdominal needle biopsy.
Fine et al. (156) assessed severe radiation morbidity in 189 patients with carcinoma of the cervix who underwent pretherapy surgical staging by a retroperitoneal (67 patients) or transperitoneal (122 patients) approach; 79 patients had previously had a laparotomy. Patients subsequently received EBRT and brachytherapy with a median dose of 85 Gy to point A. In patients receiving para-aortic irradiation, a median of 45 Gy was administered. Of the 189 patients, 36 (34.9%) had radiation-induced complications requiring surgical repair or causing death; 47 received extended-field irradiation, and 13 (27.7%) had severe complications. The incidence of major treatment-related morbidity was similar (36.6%) in 15 patients who did not receive extended-field irradiation. There was a significant correlation between the incidence of complications and type of lymphadenectomy performed and whether the patient had a prior laparotomy (see Table 66.11). Patients who received <60 Gy to point A had significantly fewer complications (20%)

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than those receiving higher doses (44%). The 5-year survival was 42% for patients evaluated through a retroperitoneal and 36% for those evaluated through a transperitoneal approach.

Potish (497) pointed out that surgical staging provides prognostic data and can accurately lead to a relatively high cure rate for patients without nodal or peritoneal metastases. Potish et al. (496) noted that more than half of the patients with advanced cervical cancer with grossly positive pelvic nodes that were debulked survived, compared with none with unresectable lymph nodes, findings closely paralleling those of Inoue and Morita (269). The potential benefit of surgical debulking and irradiation will be small in patients with early or very advanced cervical carcinoma.

More recently, para-aortic node sampling has been performed through a laparoscopic approach; the procedure is well tolerated, recovery is prompt, and yield has been reported to be adequate (106,164).

Preservation of the Ovaries and Ovarian Function

In a survey of 124 patients who had undergone radical hysterectomy and lymphadenectomy with ovarian transposition, 68 responders were premenopausal at the time of surgery. Six of 30 women (20%) with ovarian preservation experienced early hormonal failure (five had one ovary and one patient had both preserved) (461). Combined-modality therapy may have a more pronounced effect on ovarian function than either irradiation or operation alone (159). Anderson et al. (18) noted that only 4/24 patients (17%) with ovarian transposition who received postoperative pelvic irradiation had continued ovarian function.

Feeney et al. (152) reported on 132 patients on whom lateral ovarian transposition was performed at the time of radical hysterectomy; 28 patients received postoperative pelvic irradiation. Fourteen of 28 patients (50%) who received pelvic irradiation had evidence of ovarian failure, in contrast to 3/104 patients (2.9%) on whom ovarian transposition was performed, without postoperative irradiation. Buekers et al. (59) also evaluated ovarian function in 102 patients with cervical cancer, 83 of whom underwent radical hysterectomy and 19 a staging laparotomy, all with ovarian preservation (80 included ovarian transposition); 26 patients received postoperative radiation therapy. After ovarian transposition without RT, 98% of patients retained ovarian function for a mean of 126 months, with menopause at a mean age of 45.8 years. When ovarian transposition and RT were added, 41% retained ovarian function for a mean of 43 months and experienced menopause at a mean age of 36.6 years.

Likewise, Morice et al. (421) reported on 107 patients treated for cervical cancer with radical hysterectomy and lymphadenectomy, 104 of whom (98%) had ovarian transposition to the paracolic gutters performed. Preservation of ovarian function was achieved in 100% for patients treated exclusively by surgery, 90% for those treated by postoperative vaginal brachytherapy, and 60% for patients treated by postoperative EBRT and vaginal brachytherapy.

Ovarian transposition or oophoropexy has been performed using laparoscopy, achieving continued hormonal function in 68% (8/11) and 50% (3/6) of the patients. Mean follow-up was 8.5 years, and mean radiation absorbed dose to the displaced ovaries was 26 Gy (363).
Stockle et al. (580) performed laparoscopic lateral ovarian transposition during staging lymphadenectomy in 11 patients with carcinoma of the cervix treated with brachytherapy (11 cases), EBRT (nine cases), and chemotherapy (two cases). Ovarian preservation was achieved in 30% of the cases. Age was the most predictive factor for ovarian function preservation.