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Systematic review of adjuvant therapy for early stage (epithelial) ovarian cancer

B Winter-Roach, L Hooper, and H Kitchener.

Review published: 2003.

CRD summary

This review assessed the effectiveness of adjuvant therapy following surgery for early ovarian cancer. The authors concluded there was no significant difference in survival between chemotherapy and radiotherapy and, that chemotherapy improved survival compared with no treatment. Toxicity and quality of life were not evaluated. Lack of assessment of the differences between included studies limits the strength of this review.

Authors' objectives

To assess the effectiveness of adjuvant treatment after surgery in women with early ovarian cancer.

Searching

MEDLINE (from 1975), EMBASE (from 1980), Cancerlit and the Cochrane CENTRAL Register were searched; the search terms were stated.

Study selection

Study designs of evaluations included in the review

Randomised controlled trials (RCTs) were eligible for inclusion.

Specific interventions included in the review

Studies of adjuvant treatment with chemotherapy or radiotherapy were eligible for inclusion. Studies of different types, doses, or regimens of a single treatment modality were excluded. The review included studies that compared adjuvant radiotherapy with no treatment; chemotherapy with radiotherapy; radiotherapy plus chemotherapy with radiotherapy alone; and chemotherapy with no treatment. The radiotherapy regimens included intraperitoneal radioactive chronic phosphate (P32) and whole abdominal-pelvic radiotherapy. The chemotherapy regimens included cisplatin-based regimens and melphalan regimens.

Participants included in the review

Studies of women with early epithelial ovarian cancer (Stage I or II) were eligible for inclusion. Only studies in which women had formal surgical staging of the cancer performed at laparotomy were included in the meta-analysis.

Outcomes assessed in the review

Studies that reported survival were eligible for inclusion. The primary outcomes in the review were overall survival and disease-free survival.

How were decisions on the relevance of primary studies made?

Two reviewers independently selected the studies for inclusion and resolved any disagreements through discussion.

Assessment of study quality

Validity was assessed on the basis of randomisation, similarity of the treatment groups with respect to prognostic factors, blinding of the outcome assessment, completeness of follow-up, and intention-to-treat analysis. The authors did not state who performed the validity assessment.

Data extraction

Three reviewers independently extracted the data using forms developed for the review. For each group, the ln hazard ratio (HR) and its variance were calculated for overall survival and disease-free survival (the methods used to derive these values were stated). Reported adverse effects were extracted from studies comparing chemotherapy with radiotherapy and chemotherapy versus no treatment.

Methods of synthesis

How were the studies combined?

Studies that reported surgical staging of the cancer were combined using a random-effects meta-analysis. The pooled HR and 95% confidence intervals (CIs) were calculated for adjuvant chemotherapy compared with radiotherapy and for adjuvant chemotherapy compared with observation (with treatment of progression of the disease). Adverse effects were tabulated by trial, but there was no synthesis.

How were differences between studies investigated?

Subgroup analyses were used to look for differences in effect between trials of chemotherapy versus whole abdominal radiotherapy and chemotherapy versus intraperitoneal P32 radiotherapy. A sensitivity analysis was performed to see the effect of platinum-based chemotherapy in comparisons of chemotherapy versus observation and chemotherapy versus radiotherapy.

Results of the review

Fifteen RCTs (3,162 women) were included. Ten of these RCTs were included in the meta-analysis.

Radiotherapy versus no treatment: the one identified RCT did not report results for each treatment arm.

Chemotherapy versus radiotherapy (5 RCTs, 862 women): in all these RCTs, the treatment groups were similar at baseline with respect to prognostic factors. There was no significant difference in overall survival or disease-free survival between chemotherapy and radiotherapy. The HR was 0.85 (95% CI: 0.62, 1.17) for overall survival and 0.94 (95% CI: 0.56, 1.59) for disease-free survival. Significant heterogeneity was found. A subgroup analysis showed no significant difference between chemotherapy and whole abdomen radiotherapy, between chemotherapy and P32 radiotherapy, or between platinum-based chemotherapy and P32 radiotherapy (the results were reported).

Chemotherapy plus radiotherapy versus radiotherapy alone (2 RCTs, 242 women): the studies compared whole abdominal radiotherapy with pelvic radiotherapy plus chemotherapy. In neither study were the treatment groups similar at baseline with respect to prognostic factors. Neither study presented extractable quantitative data. The individual studies showed no significant difference in survival between the treatments.

Chemotherapy versus no treatment (5 RCTs, 1234 women): 75% of the patients came from 2 RCTs. The RCTs were all of a good quality. The meta-analysis showed that chemotherapy significantly improved overall survival and disease-free survival. The HR was 0.71 (95% CI: 0.63, 0.80) for overall survival and 0.68 (95% CI: 0.59, 0.79) for disease-free survival.

The analysis was repeated after removing the one RCT that did not use a platinum-based chemotherapy regimen. Neither the results for overall survival nor disease-free survival were altered (the results were reported).

Authors' conclusions

There was no significant difference in survival between chemotherapy and radiotherapy. Chemotherapy improved survival compared with no treatment.

CRD commentary

The review question was clear in terms of the study design, intervention, participants and outcomes. Several relevant sources were searched and the search terms were stated. It was not stated whether any language limitations had been applied. More than one reviewer independently selected the studies and extracted the data, thus reducing the potential for bias and errors. Validity was assessed using established criteria and the results were tabulated. Relevant information on the included studies was tabulated. Appropriate methods were used to pool the data and statistical heterogeneity was assessed. Evidence obtained from higher quality RCTS was highlighted. The authors discussed some of the limitations of the studies. For example, the suboptimal dose of chemotherapy and the lack of consistent reporting of adverse effects and quality of life. The evidence presented appears to support the authors' conclusions.

Implications of the review for practice and research

Practice: The authors stated that women who have been adequately staged with well-differentiated ovarian cancer confined to one or both ovaries with an intact ovarian capsule (FIGO Stages IA/IB) can be managed by observation. Other women should be offered adjunctive treatment with platinum-based chemotherapy

Research: The authors stated that potential adjunctive therapies for early-stage ovarian cancer should be assessed for toxicity and quality of life, as well as efficacy.

Bibliographic details

Winter-Roach B, Hooper L, Kitchener H. Systematic review of adjuvant therapy for early stage (epithelial) ovarian cancer International Journal of Gynecological Cancer 2003; 13(4): 395-404. [PubMed: 12911714]

Indexing Status

Subject indexing assigned by NLM

MeSH

Adult; Aged; Antineoplastic Combined Chemotherapy Protocols /therapeutic use; Carcinoma /mortality /pathology /therapy; Chemotherapy, Adjuvant; Confidence Intervals; Disease-Free Survival; Female; Humans; Middle Aged; Neoplasm Staging; Ovarian Neoplasms /mortality /pathology /therapy; Ovariectomy /methods; Probability; Prognosis; Radiotherapy Dosage; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Risk Assessment; Survival Analysis

AccessionNumber

12003001723

Database entry date

31/12/2004

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 12911714