CA 125, PET alone, PET–CT, CT and MRI in diagnosing recurrent ovarian carcinoma: A systematic review and meta-analysis

https://doi.org/10.1016/j.ejrad.2008.02.019Get rights and content

Abstract

Background and purpose

Ovarian cancer is the commonest tumor in female patients with a propensity for recurrence even after primary chemotherapy in early stage. The accuracy of CA 125, PET alone, PET–CT, CT and MRI in diagnosing the recurrent ovarian carcinoma has never been systematically assessed, and present systematic review was aimed at this issue.

Methods

We searched for articles published from January 1995 to November 2007, inclusion criteria including: articles were reported in English or Chinese; CA 125, PET whether interpreted with or without the use of CT, CT or MRI was used to detect recurrent ovarian carcinoma; Histopathologic analysis and/or close clinical and imaging follow-up for at least 6 months. We extracted data to calculate sensitivity, specificity, SROC curves and AUC and to test for heterogeneity.

Result

In 34 included studies, CA 125 had the highest pooled specificity, 0.93 (95% CI: 0.89–0.95); PET–CT had highest pooled sensitivity, 0.91 (95% CI: 0.88–0.94). The AUC of CA 125, PET alone, PET–CT, CT and MRI were 0.9219, 0.9297, 0.9555, 0.8845 and 0.7955, respectively. Results of pairwise comparison between each modality demonstrated AUC of PET, whether interpreted with or without the use of CT, was higher than that of CT or MR, p < 0.05. The pooled sensitivity, pooled specificity and AUC showed no statistical significance between PET alone and PET–CT. There was heterogeneity among studies and evidence of publication bias.

Conclusion

PET–CT might be a useful supplement to current surveillance techniques, particularly for those patients with an increasing CA 125 level and negative CT or MR imaging. However, regarding to diagnostic accuracy, interpreted CT images may have limited additional value on PET in detecting recurrent ovarian cancer.

Introduction

It is widely known that carcinoma of the ovary is the third commonest tumor of the female genital tract after carcinomas of the cervix and endometrium; however, its prognosis is relatively poor since it accounts for approximately half of all deaths caused by those tumors [1], [2]. It is initially sensitive to platinum-based cytotoxic chemotherapy after the primary cytoreductive surgery. The overall response rate with primary therapy is about 80%. However, 60–70% of patients will eventually relapse [3] and the median survival time of patients with recurrent ovarian cancer ranges from 12 to 24 months [4]. The value of early detection of recurrent disease continues to be debated, and there is no evidence to support which early treatment for its recurrence can produce more prolonged survival [5]. However, with the development of new target drugs, the accurate diagnosis of its recurrent will probably afford a better chance that its prolonged remission and sustained quality of life could be attained due to its appropriate salvage treatment [6].

Diagnostic second-look laparotomy (SLL) is, conventionally, considered to be the gold standard of the detection of recurrent ovarian carcinoma [7], [8], [9], however, since SLL is still an invasive modality which may have the potential surgical complications and high anesthesia risk, there is the need for a noninvasive diagnostic tool. Although extensive researches have been performed with regard to the diagnostic performance of noninvasive methods for the detection of recurrent ovarian carcinoma, such as CA 125, PET alone, PET–CT, CT and MRI, the optimal diagnostic tool has yet not been identified.

Havrilesky [10] performed a meta-analysis to assess the diagnostic performance of FDG-PET in comparison with that of CT and MRI in the patients with ovarian cancer; however, it did not assess another important noninvasive method—CA 125, which is widely used both in surveillance and follow up. Furthermore a relatively small population of recurrent ovarian cancer patients was conducted in only 5 studies included. Thus, the aim of our study was to perform a comprehensive systematic review to obtain the overall diagnostic performance of CA 125, PET alone, PET–CT, CT and MRI for the detection of recurrent ovarian cancer on a per-patient and a per-lesion basis, which to our knowledge, had not previously been studied.

Section snippets

Literature search

A comprehensive computer literature search [11] of abstracts about studies in human subjects was performed to identify articles about the diagnostic performance of CA 125, PET (interpreted with or without the use of CT), CT and MRI for the detection of recurrent ovarian cancer. The MEDLINE and EMBASE databases, from January 1995 to November 2007, were used with the following key words (“PET” OR “positron emission tomography” OR “FDG” OR “fluorodeoxyglucose” OR “CT” OR “computed tomography” OR

Literature search and study design characteristics

Our research yielded 272 primary studies, of which 238 (87.5%) were excluded (Fig. 1). The reasons for exclusion were (a) researchers in the articles did not use histopathologic analysis or close clinical and imaging follow-up for at least 6 months (n = 195). (b) Researchers in the articles did not use report data that could be used to construct or calculate true-positive, false-positive, true-negative and false-negative (n = 34). (c) Researchers used sequential test combinations (n = 3). (d) Data

Discussion

It is widely known that recurrence is often a major clinical problem for patients who have undergone surgery due to malignant tumors, in particular ovarian cancer has a propensity for recurrence even after primary chemotherapy in early-stage tumor [55], so clinical follow-up is crucial for patients with ovarian cancer. This meta-analysis focused on evaluating the diagnostic ability of CA 125, PET (interpreted with or without the use of CT), CT and MRI, which are the widely used noninvasive

Conclusion

This meta-analysis was the first report that assessed and compared summary estimates of overall diagnostic ability for those noninvasive methods that were currently used for detecting recurrent ovarian cancer. If CA 125, PET alone, PET–CT, CT and MRI were compared with each other, the results of our meta-analysis demonstrated that PET–CT might be a useful supplement to current surveillance techniques, particularly for those patients with an increasing CA 125 level and negative CT or MR imaging,

References (70)

  • M. Zimny et al.

    2-[Fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography in the diagnosis of recurrent ovarian cancer

    Gynecol Oncol

    (2001)
  • E.A. Hauth et al.

    Evaluation of integrated whole-body PET/CT in the detection of recurrent ovarian cancer

    Eur J Radiol

    (2005)
  • M. Murakami et al.

    Whole-body positron emission tomography and tumor marker CA125 for detection of recurrence in epithelial ovarian cancer

    Int J Gynecol Cancer

    (2006)
  • B. Simcock et al.

    The impact of PET/CT in the management of recurrent ovarian cancer

    Gynecol Oncol

    (2006)
  • M.M. Thrall et al.

    Clinical use of combined positron emission tomography and computed tomography (FDG-PET/CT) in recurrent ovarian cancer

    Gynecol Oncol

    (2007)
  • K. Behbakht et al.

    Clinical characteristics of clear cell carcinoma of the ovary

    Gynecol Oncol

    (1998)
  • P.G. Kluetz et al.

    Combined PET/Ct imaging in oncology. Impact on patient management

    Clin Positron Imaging

    (2000)
  • M. Martinelli et al.

    7 Survey of results of whole body imaging using the PET/CT at the University of Pittsburgh Medical Center PET facility

    Clin Positron Imaging

    (2000)
  • S. Makhija et al.

    Positron emission tomography/computed tomography imaging for the detection of recurrent ovarian and fallopian tube carcinoma: a retrospective review

    Gynecol Oncol

    (2002)
  • L. Williams et al.

    Secondary cytoreductive surgery at second-look laparotomy in advanced ovarian cancer: a Gynecologic Oncology Group Study

    Gynecol Oncol

    (1997)
  • B. Patsner et al.

    Does serum CA-125 level prior to second-look laparotomy for invasive ovarian adenocarcinoma predict size of residual disease?

    Gynecol Oncol

    (1990)
  • G. Zanetta et al.

    Ultrasound, physical examination, and CA 125 measurement for the detection of recurrence after conservative surgery for early borderline ovarian tumors

    Gynecol Oncol

    (2001)
  • N. Einhorn et al.

    Factors influencing survival in carcinoma of the ovary. Study from a well-defined Swedish population

    Cancer

    (1985)
  • C.C. Boring et al.

    Cancer statistics, 1994

    CA Cancer J Clin

    (1994)
  • J.S. Berek et al.

    Surgery during chemotherapy and at relapse of ovarian cancer

    Ann Oncol

    (1999)
  • D.K. Armstrong

    Relapsed ovarian cancer: challenges and management strategies for a chronic disease

    Oncologist

    (2002)
  • A.J. Megibow et al.

    Accuracy of CT in detection of persistent or recurrent ovarian carcinoma: correlation with second-look laparotomy

    Radiology

    (1988)
  • E. Rubinstein et al.

    Clinical aspects of second-look laparotomy in ovarian cancer

    Ann Chir Gynaecol

    (1986)
  • D.L. Sackett et al.

    The architecture of diagnostic research

    BMJ

    (2002)
  • P. Whiting et al.

    The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews

    BMC Med Res Methodol

    (2003)
  • J.L. Fleiss et al.

    The comparison of proportions from several independent samples: estimation of the marginal mean proportion

  • L.E. Moses et al.

    Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations

    Stat Med

    (1993)
  • J.J. Deeks

    Systematic reviews in health care: Systematic reviews of evaluations of diagnostic and screening tests

    BMJ

    (2001)
  • W.L. Deville et al.

    Conducting systematic reviews of diagnostic studies: didactic guidelines

    BMC Med Res Methodol

    (2002)
  • T.B. Huedo-Medina et al.

    Assessing heterogeneity in meta-analysis: Q statistic or I2 index?

    Psychol Methods

    (2006)
  • Cited by (0)

    1

    They contributed equally to this work as first author.

    View full text