| Background: Meta-analysis is defined as the statistical analysis of a collection of analyticalresults for the purpose of integrating the findings. Such analyses are becoming increasinglypopular in medical research, where information on efficacy of a treatment is available froma number of clinical studies with similar treatment protocols. If these studies are consideredseparately, each study is either too small or too limited in scope to come to unequivocal orgeneralized conclusions about the effect of treatment. Combining the findings across suchstudies represents an attractive alternative to strengthen the evidence about the treatmentefficacy.Cervical cancer is the second most common cancer among women worldwide and themain cancer that affects women in the Sub-Sahara and Africa, Central America and South–Central Asia. A significant decline in incidence and mortality have been seen in NorthAmerica, parts of Europe, Australia and New Zealand where screening programs have beenimplemented for some time.There are two cell types present (squamous and glandular) and cervical cancers tend tooccur where the two cell types meet. The main cause of cervical cancer is a virus called HPV(human papillomavirus). HPV is sexually transmitted and sexual activity increases the riskfor infection with HPV and for cervical cancer. The standard management of cervical cancerdepends on clinical stage and tumor volume. Controversies are the selection of NeoadjuvantChemotherapy (NC) to pelvic radiation did improve survival for high-risk patients, orSurgery Followed by Radiotherapy for patient of cervical Stage IB and IIA. Thus, we usedmeta-analysis to evaluate the adverse effects to the treatment and survival outcome of cervical cancer stage IB and IIA treatment with (1) NC first (2) or surgery first or (3) surgeryfollowed by radiotherapy to determine the best option for cervical cancer treatment.Methods: A systematic review of literature and published studies between1974and2012incervical treatment stage IB and IIA was performed and a meta-analysis of identified studieswas carried out. We searched the following databases: Pub Med, the Lancet, ElsevierGynecological Oncology, Elsevier EJSO, Gynecological Radiology, Med Line, Cross RefMed Line, Oncology group publications and Cancer literature. All eligible studies wereevaluated and there were14studies among them to count on because of the number ofpatients and sufficient follow up was conducted with patients. The outcomes of interest wereadverse effects to the treatment, follow up, recurrence rate and overall survival (OS) forcervical cancer patients. All full article texts were obtained for further evaluation. After thereview of the researches, exclude the studies that not up to the standard. Meta-analysis wasperformed and the summary information from eligible studies was estimated to calculateOdd ratio (OR) and95%confidence interval (CI).Results:After reviewing the researches, trials and published articles, we chose fourteenstudies. Of the14, we used10of the studies, which were eligible for meta-analysis and fitthe criteria. The average sample size was190patients (from45to611patients). Theoutcomes of interest were adverse effects to the treatment and the overall survival (OS),complications and recurrence. The follow-up time was from two months to two hundred andforty nine months. The studies were published between1974-2012and included nineretrospective studies, andone randomized study. Of ten included trials, three trials wereconducted in Thailand, two in Italy and the United States of America, and one in China andKorea. Seven studies reported the adverse effects to the treatment of the different treatmentof this study including symptomatic lymphocyst, lymphedema, radiation hemorrhagiccystitis,gastro-intestinal toxicity, vomiting, nausea, bowel obstruction or cystitis and proctitis, gallstone and pelvic abscess.Complication rate differs due to the treatment applied: surgeryplus NC or surgery plus radiotherapy. Also leukopenia or neutropenia were included in thestudy together with lymphaedema. Presence of (+) lymph nodes and (-) lymph nodes are alsorecorded in seven trials. Studies showed the data of the overall survival calculated by theKaplan-Meier Method to calculate Hazard ratio (HR) and95%confidence interval (CI).Nine studies had treated patients in stage IB-IIA, and one had treated patients in stage IA2-IIA. Eight studies reported the5-year overall survival (OS), one study reported2-yearoverall survival (OS), and one study reported3and5-year survival. The5-year disease-freesurvival rate were different from one trial to another due to the changes in treatmentprocedures. The shortest median follow up reported was19months, while the longestreported was84months. The follow up shown in the study gave idea about the presence ofcomplication and recurrence or without recurrence. The number of patients alive was despiteproblems from surgery or combined therapy. The follow up of treated patients also showed ifpatients died from other diseases or due to recurrence. Results of10trials indicated thatpatients developed recurrence were between3.3%and42%and this was also changed in thesurgery group than in radiotherapy treatment and NC. Meta analysis and systematic reviewproved that for cervical cancer stage IB and IIA the best option of treatment after reviewingthe complications, recurrence and overall survival rate for5years is radical hysterectomywith lymph nodes removal followed by radiotherapy. Of the ten studies, five studies havestatistically significant treatment effects (Kim et al.,2008; Siriwaranya et al.,2003;Sittidilokratna et al.,2010; Monk et al.,1998; Landoni etal.,1997). The significant oddratios (OR) at the5%level (P<0.05) of having a favorable outcome among the studies usingradiotherapy after radical hysterectomy were0.097(95%CI,0.055–0.1771)(Monk et al.,1994),1.71(95%CI,1.254–0.2.347)(Landoni et al.,1997), and3.5(95%CI,1.707–7.197)(Siriwaranya et al.,2003).In other hand, the significant odds ratios (ORs) at the5%level (P<0.05) of having a favorable outcome among the studies using NC plus radiotherapy afterradical hysterectomy were3.973(95%CI,1.934–8.16)(Kim et al.,2008), and2.327(95%CI,1.637–3.306)(Sittidilokratna et al.,2010). However, the width of CI for Kim study mayindicate that lessprecise estimates for their results.Conclusions:After using systematic review and Meta analysis, we indicated that the bestoption of treatment cervical cancer stage IB and IIA after reviewing the complications,recurrence and overall survival rate for5years is radical hysterectomy with lymph nodesremoval followed by radiotherapy. While, radical hysterectomy and radiotherapy pluslymphadectomy produce favorable results with low morbidity. In addition, surgery plusradiotherapy increase the survival rate and decrease the pelvic recurrence, whereas NC didimprove survival for high-risk patients. Based on our result, we recommend thatpostoperative radiation be considered in the management of patients with stage IB-IIAcervical carcinomas found to have regional lymph node metastases; however, alternate formsof therapy deserve consideration when the tumor extends to both the parametrium and pelviclymph nodes. |
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