Date Published: July 3, 2019
Publisher: Public Library of Science
Author(s): Emma R. Allanson, Aime Powell, Max Bulsara, Hong Lim Lee, Lynette Denny, Yee Leung, Paul Cohen, Sudeep Gupta.
To investigate morbidity for patients after the primary surgical management of cervical cancer in low and middle-income countries (LMIC).
The Pubmed, Cochrane, the Cochrane Central Register of Controlled Trials, Embase, LILACS and CINAHL were searched for published studies from 1st Jan 2000 to 30th June 2017 reporting outcomes of surgical management of cervical cancer in LMIC. Random-effects meta-analytical models were used to calculate pooled estimates of surgical complications including blood transfusions, ureteric, bladder, bowel, vascular and nerve injury, fistulae and thromboembolic events. Secondary outcomes included five-year progression free (PFS) and overall survival (OS).
Data were available for 46 studies, including 10,847 patients from 11 middle income countries. Pooled estimates were: blood transfusion 29% (95%CI 0.19–0.41, P = 0.00, I2 = 97.81), nerve injury 1% (95%CI 0.00–0.03, I2 77.80, P = 0.00), bowel injury, 0.5% (95%CI 0.01–0.01, I2 = 0.00, P = 0.77), bladder injury 1% (95%CI 0.01–0.02, P = 0.10, I2 = 32.2), ureteric injury 1% (95%CI 0.01–0.01, I2 0.00, P = 0.64), vascular injury 2% (95% CI 0.01–0.03, I2 60.22, P = 0.00), fistula 2% (95%CI 0.01–0.03, I2 = 77.32, P = 0.00,), pulmonary embolism 0.4% (95%CI 0.00–0.01, I2 26.69, P = 0.25), and infection 8% (95%CI 0.04–0.12, I2 95.72, P = 0.00). 5-year PFS was 83% for laparotomy, 84% for laparoscopy and OS was 85% for laparotomy cases and 80% for laparoscopy.
This is the first systematic review and meta-analysis of surgical morbidity in cervical cancer in LMIC, which highlights the limitations of the current data and provides a benchmark for future health services research and policy implementation.
Cervical cancer is the third most common malignancy in women worldwide and performs poorly in all objective measurements of outcomes in less developed countries. The disease is a notable example of an extreme global health disparity with almost all cervical cancers, and the deaths caused by them, occurring in low and middle-income countries (LMIC). Contributors to this inequity are complex and multifaceted and include insufficient access to HPV vaccines and screening, and lack of trained health care professionals, radiation services and infrastructure, that prohibit reductions in cervical cancer incidence and mortality within these countries .
This systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines . We searched Pubmed, Cochrane, the Cochrane Central Register of Controlled Trials, Embase, LILACS, and CINAHL to identify all relevant articles published January 1, 2000, to June 30, 2017, without language restriction. The year 2000 was chosen as the limit of the search for both pragmatic reasons and in order that the findings were reflective of current practice.
Fig 1 shows the selection of studies. A total number of 56 articles met the study inclusion criteria. Two studies which reported on trachelectomy only were excluded from the meta-analysis[32, 33]. One high quality study included stage 4 cancers (the remainder included only early stage disease 1A-2B) and was excluded from the analysis. Figs 2 and 3 present the risk of bias assessment in the included high quality studies. Studies were high quality in most domains; however, it was common that stage of disease was not controlled for, and that the assessment of the outcome and the method of assessment were not adequately described.
To our knowledge, this is the first systematic review and meta-analysis of morbidity after primary surgical management of cervical cancer specifically in LMIC, although only data from middle-income countries (MIC) were included in the meta-analysis. The incidence of complications in this meta-analysis is largely comparable to those reported in high-income countries (HIC). Blood transfusions are reported in HIC at up to 25% for minimally invasive surgical approaches for cervical cancer and up to 75% for laparotomy, and so our findings of 10% and 42% respectively are consistent with published studies that have been conducted in well resourced settings. This may however also reflect differing resources and thresholds for transfusions in LMIC. In HIC 1.2% and 2.8% of women develop fistula (ureterovaginal and vesicovaginal) and pulmonary embolism respectively following surgery for cervical cancer. Ureteric injuries following laparotomy and radical hysterectomy for cervical cancer were reported to occur in 2.48% of cases in a review of nearly 400,000 hysterectomies in the United Kingdom (UK). The reported incidence of complications is similar or lower in this meta-analysis and may represent publication bias. However, our findings suggest that, morbidity following surgery for cervical cancer in MIC appears to compare favourably to the reported incidence in HIC.
This is the first systematic review and meta-analysis of surgical morbidity in cervical cancer in LMIC and provides a benchmark for future health services research and policy implementation. Surgery is the cornerstone of management in early stage cervical cancer and is likely to remain a major treatment modality in LMIC for many years; we must as a global oncology community mobilise to ensure the foundations for health advocacy and program development are in place, including surgical morbidity registries.