Description of the condition
Cancer is a leading cause of death worldwide (WHO 2008). Gynaecological cancers (i.e. cancers affecting the ovaries, uterus, cervix, vulva, and vagina) are among the most common cancers in women. Globally, a woman's risk of developing cancer of the cervix, ovaries, and uterus by the age of 65 is 2.2%; cancers of the vulva and vagina are less common. Gynaecological cancers account for 25% of all new cancers diagnosed amongst women up to 65 years of age in developing countries, compared with 16% in the developed world (GLOBOCAN 2008).
Uterine cancer tends to be a disease of the elderly and obese female population. More than 80% of these cases arise from the endometrium. Endometrial cancer is the most common genital tract cancer among women in developed countries. The worldwide risk of a woman developing cancer of the uterus by the age of 65 is 0.59%, and the rate is twice as high in developed countries compared with developing countries (GLOBOCAN 2008). The cornerstone of treatment of women with endometrial cancer is surgery, followed, in some patients, by radiotherapy with or without chemotherapy. The prognosis for women with early-stage disease is good, and many women are cured by surgery alone. Women presenting with advanced or recurrent disease have a much poorer prognosis, with a median overall survival of 9 to10 months (Thigpen 2001; Thigpen 2004).
Cervical cancer is the second most common cancer among women up to 65 years of age, and it is the most frequent cause of death from gynaecological cancers worldwide; its incidence is twice as high in developing countries, where women often present with advanced-stage disease (GLOBOCAN 2008). Over the past three decades, it has become apparent that the main risk factor for the development of cervical cancer is persistent infection by the human papillomavirus (HPV). More than 100 subtypes of HPV are known; the subtypes at greatest risk for forming cancer are subtypes 16 and 18, which are responsible for most cases of cervical cancer. Women with cervical cancer are treated primarily by surgery or chemoradiotherapy; a small number require both modalities. For early-stage small-volume disease, surgery or radiotherapy alone appears to be equally effective (Eifel 1991); however, surgery may be more beneficial in younger women, in that ovaries can be preserved and vaginal atrophy and stenosis avoided.
Cancer of the vulva is rare; when coupled with cancer of the vagina, it accounts for less than 1% of all cancer cases and 8% of gynaecological cancers diagnosed in the UK. In 2008, 1157 new cases of vulval cancer were diagnosed in the UK, equating to a European age-standardised incidence rate of 2.5 per 100,000 female population (Cancer Registration in NI 2011;Cancer Registrations in Wales 2010; ISD Scotland 2011; Office for National Statistics 2011). An estimated 27,000 women worldwide are diagnosed with vulval cancer each year (Sankaranarayanan 2006), and it has been estimated that the lifetime risk of developing vulval cancer is around 1 in 293 for women in the UK. The management of women with vulval cancer usually involves surgery initially, which is necessary to stage and control the disease and to prevent local recurrence. Radiotherapy may be given as a primary form of treatment in those women with larger, more advanced lesions involving bladder or rectum, or who are considered unsuitable for surgery. It may also be used as an adjunct to surgery in patients who have inadequate surgical resection margins or lymph node involvement.
The biology of recurrent ovarian cancer differs from that of other gynaecological cancers; its management is therefore the subject of a separate review (Al Rawahi 2010).
Description of the intervention
Unfortunately, given the nature of the disease, in most patients with cancer, the condition will recur or progress at some point in their lives. Cancer recurrence is defined as the return of cancer after treatment and after a period of time during which the cancer is undetectable. Progression is seen when cancer metastasises or worsens. The difference between recurrence and progression is not always clear, and the definition of recurrence includes no standard period of time; however, most would consider a cancer to be recurrent when it appears after 12 months of a disease-free state (American Cancer Society 2011).
Although the management of early-stage cancers is relatively straightforward, with lower associated morbidity and mortality, the surgical management of advanced and recurrent malignancies is significantly more complicated, often requiring very extensive procedures. The mainstay for treatment success in terms of locoregional control and long-term survival is resection of the pelvic tumour with clear margins (Höckel 2006).
Pelvic exenterative surgery involves removal of part or all of the pelvic organs, namely, the rectum (with or without the sigmoid colon), bladder, reproductive organs (including vagina and vulva), pelvic peritoneum, and sometimes the perineum, with reconstruction. Since it was first described by Brunschwig in 1948, the development of newer techniques of resection and pelvic reconstruction over the past few decades has led to a considerable reduction in the frequency of complications and perioperative mortality (Brunschwig 1948; Höckel 2006; Höckel 2008; Lawhead 1989; Shingleton 1989; Stanhope 1990; Symmonds 1975). The reconstruction of pelvic floor defects after extensive surgical resection of genital malignancies presents multiple challenges. The pelvic dead space predisposes patients to problems with ileus, haematomas, abscesses, and fistulae. The reconstruction of pelvic wall defects with omental flaps, bowel anastomoses, and the creation of neo-vaginas has decreased some of these complications (Schmidt 2012; Soper 1989; Buchsbaum 1973). In recent years, surgeons undertaking exenterative surgery aim to create neo-vaginas from bowel segments, to achieve primary anastomosis of the rectosigmoid colon, and to create a continent bladder where possible, giving patients a much improved quality of life (Schmidt 2012).
The most common indication for exenteration is cervical carcinoma that is persistent or has recurred after radiotherapy (Höckel 2006). The intent of exenterative surgery should be resection of all tumour with the aim of cure. It is a radical, often mutilating procedure associated with significant post-operative morbidity, and is a major undertaking for both patient and surgeon, but it may be the only curative intervention in women with recurrent malignant disease. The reduction in mortality over the past few decades is the result of improvements in surgical and anaesthetic techniques, the use of prophylactic antibiotics, thromboprophylaxis, and intensive care monitoring. Despite this, peri-operative and post-operative morbidity rates continue to remain significant, albeit on the decrease. As a result of various improvements in peri-operative management, treatment-related mortality has dropped to less than 10% and 5-year survival has increased to 40% to 50% for patients with advanced pelvic malignant disease that was otherwise untreatable (Höckel 2006). In locally advanced and recurrent pelvic malignancies, adequate clearance often cannot be achieved without resection of other pelvic viscera.
Women with progressive disease are likely to have tumours that differ biologically from tumours found in those with recurrent disease, have a poorer prognosis, and are unlikely to be offered exenterative surgery as part of their treatment. We have therefore limited this review to discussion of women with recurrent disease regardless of the type of primary treatment received.
Why it is important to do this review
Exenterative surgery in the management of persistent or recurrent cancer after initial treatment is difficult and is associated with significant peri-operative morbidity and mortality. However, it provides these women with a chance of cure that otherwise may not be possible. The aim of this review is to examine the available evidence for exenterative surgery in the management of women with recurrent gynaecological cancer. To our knowledge, no previous systematic reviews have addressed this subject.