Radical Hysterectomy for Carcinoma of the Uterine Cervix
Marc J. Kleinberg and Ronald W. Alvarez
Table Of Contents
Marc J. Kleinberg, MD
Ronald W. Alvarez, MD
GENERAL CONSIDERATIONS FOR RADICAL HYSTERECTOMY
TYPES OF RADICAL ABDOMINAL HYSTERECTOMY
SPECIFIC INDICATIONS FOR RADICAL HYSTERECTOMY AND OUTCOMES
COMPLICATIONS OF RADICAL HYSTERECTOMY
Interest in developing a surgical cure for carcinoma of the uterine cervix predates the turn of the 20th century. Working independently, Clark,1 Rumpf,2 and Ries3 described the radical abdominal hysterectomy with lymph node dissection in the mid-1890s. In 1902, citing the unacceptable surgical mortality of the abdominal approach, Schauta advocated the radical vaginal hysterectomy.4 Wertheim criticized the vaginal procedure for its failure to include an assessment of the lymph nodes. Shortly thereafter, Wertheim published a series of cases describing his experience with the radical abdominal hysterectomy and selective pelvic lymph node sampling.5,6,7
In spite of these early attempts, radical pelvic surgery was not enthusiastically embraced owing to excessive morbidity and mortality; radiation remained the mainstay of treatment for cervical cancer during the first half of the 20th century. Nevertheless, some surgeons remained interested in refining the procedure. In 1934, Taussig reported a survival benefit when pelvic lymphadenectomy was added to standard radiotherapy.8 During the following decade, Meigs led the revival of interest in radical surgery for carcinoma of the cervix. He modified the operation described by Wertheim to include more extensive removal of the parametria and a complete pelvic lymphadenectomy.9,10,11 Although complications, particularly fistulas, remained a significant obstacle to the widespread endorsement of the radical hysterectomy for the treatment of cervical cancer, the mortality associated with this procedure was virtually eliminated as antibiotics and blood transfusions became increasingly utilized.
|GENERAL CONSIDERATIONS FOR RADICAL HYSTERECTOMY|
Appropriate selection is critical when considering whether surgical therapy would be most beneficial to a patient with carcinoma of the cervix. Some patients are considered poor surgical candidates because of their comorbidities. Frequently cited medical contraindications to radical hysterectomy include cardiac, pulmonary, and renal diseases. Thromboembolism and coagulopathy should be considered as well. Conversely, certain situations lend themselves to primary surgical therapy. Complications associated with radiation may preclude its use in patients with pelvic adhesive or inflammatory disease, previous genitourinary or intestinal surgery, inflammatory bowel disease, and anatomic anomalies (e.g. pelvic kidney).
Many gynecologic oncologists favor nonoperative treatment in elderly patients. Sixty-five years of age is frequently cited as the limit for consideration of radical hysterectomy. However, some authors have found that the morbidity and survival of older patients is comparable with that of younger patients.12,13,14 Thus, it seems prudent to determine whether a surgical approach is appropriate and safe based on an assessment of risk factors and comorbidities independent of chronologic age.
Obesity is frequently associated with medical comorbidities that preclude consideration of radical hysterectomy. Furthermore, concerns about the feasibility of performing adequate resection and the exposure of obese patients to intraoperative and postoperative complications have discouraged some surgeons from considering these patients as surgical candidates. Recently, this position has been reconsidered; several authors have pointed out that, in carefully selected obese patients, radical hysterectomy can be performed adequately, safely, and effectively, although operative time and blood loss may be greater.14,15,16
Ovarian preservation is desirable in many instances. Indeed, this is one of the major advantages of surgical therapy in young patients who would otherwise require postoperative hormone replacement. Ovarian metastases are so rare (<1%) when squamous carcinoma is present that consideration of oophorectomy may be indicated only when there is gross spread to the adnexa or concomitant ovarian pathology or the patient is menopausal.17,18 In contrast, the risk of ovarian metastases has been reported to be as high as 19% for patients with stage I or II adenocarcinoma of the cervix, prompting some to recommend bilateral oophorectomy when this histologic diagnosis is known preoperatively.17,19,20 Importantly, care should be taken to reposition the ovaries outside the pelvis in the event that postoperative radiation is needed21; ovarian failure can be reduced to as low as 17% when this procedure is combined with shielding during adjuvant radiotherapy.22,23
Sexual function is an important consideration and should be discussed with all patients regardless of their age. Although the vagina is invariably shortened after a radical hysterectomy, vaginal length can be restored when sexual activity resumes. Moreover, the vaginal epithelium and caliber remain relatively unchanged with surgery; irreversible atrophy and stenosis of the vagina occur frequently with radiation, leading to sexual dysfunction in up to 78% of patients treated with radiotherapy.24,25 Nevertheless, some surgically treated patients will have sexual dysfunction related to neurovascular damage or alterations in body image and self-esteem.26,27,28
Diagnostic evaluation occasionally influences treatment planning. The International Federation of Gynecology and Obstetrics (FIGO) advocates clinical staging of cervical carcinoma based on physical examination findings and select, widely available diagnostic studies. However, it is well known that clinical staging is frequently inaccurate; a substantial number of patients who undergo surgical treatment are found to have metastases that upstage their disease29,30,31,32 or benign findings that downstage their disease.30 Improved imaging studies such as high-resolution computed tomography,33,34,35,36 magnetic resonance imaging,35,36,37 lymphangiography,38,39 and positron emission tomography40,41 may reveal extrauterine disease that cannot be cured with standard surgical techniques. However, these radiographic studies are imperfect because they fail to detect micrometastases that may impart a poor prognosis for surgical patients. Additionally, some clinicians advocate pretreatment surgical staging, typically using an extraperitoneal approach.42,43,44 Although the actual survival benefit conferred by such procedures may be limited,45 it is a useful adjunct in investigational settings.
|TYPES OF RADICAL ABDOMINAL HYSTERECTOMY|
In 1974, Piver and colleagues proposed a new classification system to clarify the ambiguities of the existing terminology used to differentiate types of abdominal hysterectomies.46 This system describes the extent of dissection of hysterectomies performed for various stages of cervical cancer, thereby identifying potential surgical complications. The following is a limited description of each procedure; a complete discourse on the technique for each type of hysterectomy can be found in several texts and atlases.47,48,49,50,51,52
The type 1 hysterectomy is commonly referred to as the extrafascial, or simple, hysterectomy. This hysterectomy removes the cervix along with the uterine corpus, but does not require mobilization of the ureter or removal of a significant amount of the parametria.
The type 2 (modified) radical hysterectomy, or Wertheim operation, requires more extensive dissection than the extrafascial hysterectomy. The central portion of the parametrial tissues is removed while minimizing disruption to the ureteral and vesical vasculature. Thus, the medial half of the uterosacral ligaments and the cardinal ligaments are removed as the uterine artery is ligated just medial to the point at which it crosses the ureter. Removal of a 1- to 2-cm portion of the upper vagina and pelvic and para-aortic lymphadenectomy are nearly always performed in conjunction with a type 2 radical hysterectomy.
The type 3 radical hysterectomy, originally described by Meigs, aims to remove as much parametrial tissue as possible. The uterosacral ligaments are transected near their origin from the sacrum. The cardinal ligaments are excised as widely as possible after the uterine artery is ligated at its origin where it branches off the hypogastric artery. Care should be taken to preserve the superior vesical artery. Removal of a 2- to 3-cm portion of the upper vagina and a pelvic and para-aortic lymphadenectomy are performed in conjunction with a type 3 radical hysterectomy (Fig. 1).
The type 4 hysterectomy is seldom used, but represents an extended radical hysterectomy. It involves complete dissection of the ureter from the vesicouterine ligament, sacrifice of the superior vesical artery, and removal of up to 75% of the vagina. The type 5 hysterectomy also has limited applicability. This procedure involves resection of involved portions of the bladder or distal ureter with subsequent ureteral reimplantation. Occasionally, it substitutes for an anterior exenteration.
|SPECIFIC INDICATIONS FOR RADICAL HYSTERECTOMY AND OUTCOMES|
FIGO defines microinvasive carcinoma of the cervix primarily by depth of stromal invasion. Stage Ia1 disease is limited to those cervical cancers with 3 mm or less of invasion. Lesions with invasion to a depth of greater than 3 mm but no more than 5 mm are considered stage Ia2. Notably, this definition does not address lymphovascular space involvement. Significant controversy surrounds the prognostic significance of this histologic finding and whether it should guide treatment planning if it is known to exist.53,54,55,56,57,58,59,60,61,62,63,64,65,66,67 Whether or not lymphovascular space involvement is present, surgical therapy for stage Ia disease is curative for nearly all patients.49,67,68,69,70,71,72,73,74,75,76,77,78,79,80
Extrafascial hysterectomy is generally considered adequate treatment for stage Ia1 cervical cancer. Ostor's review of the literature reveals that in spite of a 3.7% risk of lymphovascular space involvement, the risk of recurrence and lymph node metastases is approximately 1% and the risk of cancer death is only 0.2%.76 Nonetheless, some gynecologic oncologists advocate the same treatment for stage Ia1 cervical cancer with extensive lymphovascular space involvement as for stage Ia2 disease. If fertility is to be preserved, a cervical conization may suffice, provided the surgical margins and postconization endocervical curettage are negative for carcinoma and dysplasia.72,78
Stage Ia2 cervical cancer is usually treated with a type 2 modified radical hysterectomy with pelvic lymphadenectomy. Hacker summarized the data on invasive lesions of 3- to 5-mm depth and found that nodal metastases occur in 7.3%, recurrences occur in 3.1%, and cancer death occurs in 2.3%.49 Lymphovascular involvement may be seen in as many as 18.4% of these patients,76 thus reinforcing the questionable significance of this finding in microinvasive disease. When future childbearing is desired, cervical conization72,78 or radical trachelectomy80 may be combined with extraperitoneal or laparoscopic lymphadenectomy.
Macroscopic early-stage tumors are also treated successfully with surgery. The type 3 radical hysterectomy with pelvic and para-aortic lymphadenectomy is used for patients with stage Ib and IIa cervical cancer. Numerous authors have found that cure rates approach 85% to 90% and are comparable with the outcomes of patients treated with primary radiotherapy.81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105
Although these studies show that a majority of patients with stage Ib carcinoma of the cervix are cured with radical hysterectomy, it became evident that patients with large tumors had significantly worse outcomes. It is now well established that primary surgical therapy for bulky (tumor diameter >4 cm) or barrel-shaped stage Ib disease is associated with a greater risk of lymph node metastases, local and distant recurrence, and cancer death.101,106,107,108,109,110,111 Unfortunately, stage Ib patients treated with primary radiotherapy also tend to have poorer outcomes as tumor size increases112, 113,114,115 because the high doses of radiation required to sterilize large tumors exceed the amount of radiation tolerated by normal tissues.
FIGO acknowledged this survival difference by modifying the staging system. There is a distinction between smaller Ib1 lesions and larger stage Ib2 tumors. However, in a review of patients with stage Ib cervical cancer who had been treated with radical hysterectomy, Finan demonstrated that stage was not an independent predictor of poor outcomes. Rather, he showed that stage imparted a worse prognosis vis-à-vis nodal metastases, and that patients with stage Ib2, node-negative disease had significantly better survival than stage Ib2, node-positive disease.116 Furthermore, the Gynecologic Oncology Group (GOG) and others have studied patients with “intermediate-risk” stage Ib tumors (including stage Ib2) treated with primary radical hysterectomy and have yet to demonstrate a survival benefit with adjuvant radiation in the absence of nodal metastases or positive surgical margins.117,118
In light of this, it is not surprising that the optimal treatment for stage Ib2 cancer of the cervix remains controversial. Currently, the treatment options include radical hysterectomy with adjuvant radiation, radical hysterectomy with neoadjuvant chemotherapy, radical hysterectomy with neoadjuvant brachytherapy, primary radiotherapy followed by extrafascial hysterectomy, primary chemoradiation, and primary chemoradiation followed by extrafascial hysterectomy.49
In select situations, recurrent or advanced cervical can be managed surgically. Five-year survival in patients with small pelvic recurrences (<2 cm) confined to the cervix treated with radical hysterectomy has been reported to be as high as 84% to 90%119,120; however, the incidence of major postoperative morbidity is 31% to 44%.119,120,121 Conservative surgical treatment of larger recurrences is ill advised, because as tumor size increases, the overall survival decreases and the incidence of surgical complications rises dramatically.121
|COMPLICATIONS OF RADICAL HYSTERECTOMY|
Radical hysterectomy can be accomplished with acceptable morbidity (<5%) in the hands of a experienced surgeon. Nevertheless, complications do occur. Predisposing factors include previous pelvic surgery or radiation, endometriosis, pelvic inflammatory disease, anatomic anomalies, obesity, and pregnancy.
Intraoperatively, the most common complication of radical hysterectomy is hemorrhage; the range of reported average blood loss is from 600 mL to 1900 mL.14,122,123,124 Injured vessels can be repaired with hemoclips or suture ligatures, although hypogastric artery ligation is sometimes required to control hemorrhage. Ureteral injury is recognized intraoperatively in less than 1% of cases,125,126 however it may occur more frequently and go unnoticed. The use of intravenous indigo carmine may help identify the site of injury. When an injured ureter needs repair, techniques such as ureteroneocystostomy, ureteroureterostomy, stenting, and retroperitoneal drainage may be required. Bladder and bowel injuries also occur, particularly when electrocautery is used inappropriately as a substitute for sharp dissection. Typically, cystotomies or enterotomies can be repaired with a two-layer closure. However, proper repair of some injuries necessitates more involved procedures such as ureteral stenting for trigone injuries or colostomy for extensive colonic injuries.
Complications that arise during the postoperative period include both early and late complications. Early complications, or those occurring within the first 30 postoperative days, may vary.123,127,128 Infectious and febrile morbidity is the most common postoperative complication. Prophylactic use of broad-spectrum antibiotics reduces the frequency of this complication.129 Postoperative bleeding may require reoperation; however, most cases are self-limited and can be treated conservatively with close observation for hemodynamic instability and blood transfusions. Clinically significant thromboembolic complications occur in approximately 5% of cases.123,127,128,130,131,132,133 Early diagnosis requires a high index of suspicion because clinical findings are frequently subtle or nonspecific. Prolonged ileus or intestinal obstruction occurs occasionally, but both conditions usually resolve with conservative management. Postoperative mortality in this era has been reduced to less than 1%.134
Voiding dysfunction in the immediate postoperative period is nearly universal; denervation of the bladder during the operation results in transient hypertonia that is gradually replaced by hypotonia.135,136,137,138,139,140,141,142,143 Bladder drainage can be achieved with suprapubic catheterization, intermittent self-catheterization, or indwelling urethral catheterization. For most patients, the ability to void returns within 2 to 3 weeks; however, voiding dysfunction may persist in approximately 5% of patients.123,127,128,144,145,146 In addition, a substantial number of patients develop persistent urinary incontinence postoperatively. Pure stress urinary incontinence, urge incontinence, and mixed incontinence have been reported, although the incidence and nature of preoperative voiding dysfunction in these patients is unknown.137,142,144,147,148
Historically, urinary tract fistulas were among the most dreaded postoperative complications. Interruption and mobilization of the vasculature of the bladder and ureters predisposes to ischemia that lends itself to fistula formation. The need for postoperative radiation therapy worsens this problem. Fortunately, the incidence of this troublesome complication is now quite low, occurring in less than 2% of cases.93,94,98,134,149 The diagnosis can be made by sequential inspection of a vaginal tampon after intravesical instillation of methylene blue followed by intravenous indigo carmine to determine whether a vesicovaginal or ureterovaginal fistula exists. Alternatively, an intravenous pyelogram or computed tomography may located the fistula. Vesicovaginal fistulas, particularly those that are small, may heal spontaneously with prolonged bladder drainage; however, larger defects and those that fail to heal with conservative management need to be repaired surgically. Ureterovaginal fistulas require stenting; if a retrograde stent cannot be passed, percutaneous nephrostomy with anterograde stenting is required.
Other late postoperative complications (arising after 30 postoperative days) may be seen as well. Fortunately, they occur less frequently. Lymphedema develops insidiously over time, making its true incidence difficult to determine. It occurs more frequently when pelvic lymphadenectomy is followed by radiation or groin node dissection. Similarly, lymphocyst formation can occur as a result of extensive pelvic lymphadenectomy. The reported incidence is only 2% to 3%134,150,151; however, many are asymptomatic and may go undetected. In the event that a lymphocyst causes ureteral obstruction or presents as a pelvic mass, percutaneous drainage or reoperation with marsupialization may be necessary. Sexual dysfunction and surgical menopause, which were previously discussed, should not be forgotten because quality of life will be important to the many survivors of early cervical cancer treated with radical hysterectomy.
In the event that invasive cancer of the cervical stump is diagnosed in a patient with a prior subtotal hysterectomy, the staging and treatment options are essentially the same as for a patient with the uterus in situ. There is no reason to believe that cancer of the cervical stump carries an inherently worse prognosis.151,152 Early-stage disease can be effectively treated with radical trachelectomy; however, adhesions from the previous surgery increase the technical difficulty of the procedure and may prevent the attainment of adequate surgical margins.154,155,156,157 If radiation is to be used, difficulty with dosing may occur because the cervical stump may be too short to properly support a tandem.
Rarely, pathologic evaluation of a simple hysterectomy specimen will reveal unsuspected invasive cervical cancer. When this occurs, further treatment is needed because of the possibility of residual disease in the vaginal cuff, parametria, or lymph nodes. Radiotherapy has been used successfully in these cases; however, the combination of surgery and radiation increases the likelihood that postoperative complications will arise. A reasonable alternative in selected patients is reoperation; radical parametrectomy with upper vaginectomy and lymphadenectomy may be curative.158,159 Unfortunately, some patients who undergo radical reoperation will still require postoperative chemoradiation for positive surgical margins or lymph node metastases. Furthermore, this is a technically difficult procedure that usually requires a cystotomy to complete and subjects the patient to a second major surgery relatively soon after the initial procedure.
Interest in the radical vaginal hysterectomy, or Schauta procedure, has recently increased as laparoscopic surgery is incorporated into gynecologic oncology. Typically, the radical vaginal hysterectomy is preceded by an extraperitoneal laparoscopic lymphadenectomy. Alternatively, a laparoscope-assisted radical vaginal hysterectomy can be performed along with the laparoscopic lymphadenectomy. Descriptions of these procedures are available.160,161,162
The treatment of cervical cancer during pregnancy poses several challenges. Diagnosis may be delayed because the possibility of cancer is overlooked in young patients and because the most common presenting symptoms, vaginal bleeding or discharge, are attributed to pregnancy-related causes. Physiologic softening of the cervix and parametria may lead to errors in staging. The significance of mode of delivery has been questioned; however, most clinicians recommend a classic cesarean section; vaginal delivery may predispose to hemorrhage or cervical laceration or may spread to the lower genital tract including the episiotomy site.163,162,164,165,166,167 Whether to proceed with immediate treatment or await fetal viability is subject to conflicting concerns for fetal and maternal safety. Traditionally, the gestational age at which treatment is deferred until fetal maturity is achieved is 20 weeks; prior to 20 weeks, treatment may commence with the fetus in utero. Because of improvements in neonatal survival with antenatal steroids and artificial surfactant, some clinicians have suggested that the gestational age at which treatment is deferred be moved back to 16 weeks.168 Regardless, treatment of early-stage carcinoma of the cervix is essentially the same as when there is no pregnancy, although surgery is preferred. Patients with early-stage disease can be treated with a radical hysterectomy. The operation is complicated by greater average blood loss,169 but made easier by the fact that planes of dissection are frequently more easily identified. If the fetus has reached viability, the operation should be preceded by a classic cesarean section. Survival is comparable with that of nonpregnant patients matched for stage of disease.170,171
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