Summary of main results
No studies were identified that compared exenterative surgery versus medical management for women with recurrent gynaecological malignancies (other than ovarian cancer, which has been examined in a separate review). Therefore the question of whether exenterative surgery is associated with a survival benefit in terms of overall and recurrence-free survival as well as other important outcomes cannot be answered by this review.
Overall survival and recurrence-free survival were specified as the primary outcomes of interest, as the purpose of exenterative surgery is to cure, but quality of life (before and after exenterative surgery) should be reported if adequate future studies are conducted, as treatment for recurrent gynaecological cancer can have a large impact on a woman's life both psychologically and physically. The prognosis for women with recurrent gynaecological cancer remains poor (GLOBOCAN 2008).
Quality of the evidence
No studies met the inclusion criteria for this review, resulting in no evidence for assessment.
Potential biases in the review process
A comprehensive search was performed, including a thorough search of the grey literature, and all studies were sifted and data extracted independently by two review authors. We were not restrictive in our inclusion criteria with regard to types of studies; we included non-randomised studies with concurrent comparison groups that used multivariate analyses, as we suspected that we would find no relevant RCTs. Without this constraint, we would have identified some studies for inclusion in the review, but the risk of selection bias coupled with small numbers would have made any sort of conclusion dubious. We attempted to ensure that we did not overlook any relevant evidence and searched a wide range of reasonable-quality non-randomised study designs (case-control studies and case series of few participants were excluded). We had set this figure as 30 a priori but were more inclusive than this during the title and abstract sift.
The greatest threat to the validity of the review is likely to be publication bias, that is, studies that did not find the treatment to be effective may not have been published. We were unable to assess this possibility, as we found no studies that met the inclusion criteria.
Agreements and disagreements with other studies or reviews
Few studies in the literature have compared exenterative surgery versus radiotherapy, and we identified no studies comparing exenterative surgery versus chemotherapy or combination therapy. The few that examined the former were excluded (reasons are given above); the main reasons for exclusion were that the numbers were too small or the studies involved a single cohort of participants (which also included non-gynaecological cancers) with no comparison group.
One of the excluded studies published by Hathout 2010 was reported as a conference abstract (no full-text copy was available); investigators examined overall survival (OS) and progression-free survival (PFS) following pelvic exenteration and radiation therapy for locally recurrent cervical cancer, as well as treatment-related toxicities. In this study, 28 women with a central pelvic recurrence were treated with pelvic exenteration or salvage radiotherapy. The initial treatment of these women consisted of radical surgery or radical radiotherapy, with a very small number receiving both treatment modalities. Of the 28 women who experienced recurrence, 13 (46.5%) received salvage radiation with brachytherapy. The remaining 15 women (53.5%) underwent pelvic exenteration. At recurrence, three-year OS was 54% in women salvaged by pelvic exenteration and 44% among those salvaged by radiation therapy. Median survival was similar in both groups at 39 months, and median PFS in women salvaged by exenteration and in those salvaged by radiation therapy was 31 months and 19 months, respectively. This study was excluded from the review because statistical adjustment was not used in any of the analyses. Although neither three-year OS nor median PFS between the groups of women was statistically significant, results demonstrate that exenterative surgery may provide some benefit over salvage radiation therapy; however, the study was at a high risk of bias.
Robertson et al. examined morbidity and survival among women treated by pelvic exenteration for gynaecological malignancy (Robertson 1994). They retrospectively reviewed 83 women who underwent exenterative surgery for an advanced gynaecological cancer or for recurrent disease following unsuccessful initial treatment. A total of 54 women underwent anterior exenteration, one woman had a posterior exenteration and the remaining 28 women had total exenterative surgery. This was primary treatment in 31 women, and the remaining 52 women were treated for recurrent disease. Although most women had a gynaecological malignancy, four women in fact had bowel cancer that mimicked a gynaecological cancer. Overall actuarial five- and 10-year survival was 41% and 36%. Both serious morbidity and operative mortality were low, with only three deaths occurring within 30 days of surgery. This study was excluded on the basis that it included only a single cohort of participants with no comparison group, and the women in the study included those with both advanced and recurrent cancer including ovarian and bowel cancer; nonetheless, the study authors demonstrated (1) that survival rates in their study compared favourably with those reported by other institutions, and (2) that for patients with limited options for treatment of advanced primary or recurrent pelvic cancer, exenterative surgery offers a reasonable prospect of survival with good quality of life.
The authors of Bramhall 1999 reported the findings of a phase 2 study of 50 participants with locally advanced pelvic tumours who underwent total pelvic exenteration, with a view to evaluating safety, tolerability and survival. Of the 50 participants, 32 women underwent exenterative surgery for recurrent cervical cancer, seven for rectal cancer, three for vulvar cancer, three for vaginal cancer, two for prostate cancer and three for other tumours. The 30-day mortality and in-hospital mortality rates were 8% and 16%, respectively. The crude morbidity rate was 62%, with 23 participants (46%) having grade III or IV toxicity. Overall median survival was 86 weeks, rising to 111 weeks for participants in whom a complete response was achieved. The study authors concluded that survival and operative mortality rates in patients undergoing exenterative surgery are comparable with those achieved with chemoradiotherapy in advanced pelvic neoplasia. In a prospective study (Park 2007), 46 women with advanced or recurrent gynaecological cancer were recruited, 44 of whom underwent pelvic exenteration (two women were excluded because of the presence of peritoneal disease). Of the 44 women, 30 underwent total exenteration, 12 had an anterior exenteration and two women had a posterior exenteration. Median disease-free survival was 24 months, and the five-year overall survival rate was 54% (it was not possible to estimate median survival time, as at least half of the women had not died during their time in the study). Twenty-one of the 44 women (48%) had relapse after exenteration, with median time to recurrence of five months. Both of these studies were excluded from the review, as they reported single cohorts of participants with no comparison group, and the latter study included women with both advanced and recurrent cancer, as well as ovarian cancer.
The Kasamatsu 2005 study identified 67 women with recurrent cervical cancer; 24 recurrences occurred centrally and 43 in the pelvic side wall. Of 24 women with a central recurrence, three underwent pelvic exenteration and five received radiotherapy. No details were given about PFS or OS in either group. This study was excluded because the numbers were deemed too small to be interpretable.
The article by Peiretti 2012 was a systematic review that identified no studies for inclusion in the review; it was therefore excluded.