The diagnostic value of PET/CT for primary ovarian cancer
Commentary by Professor Jonathan Carter
The article:
Risum S, Hogdall C, Loft A, et al. The diagnostic value of PET/CT for primary ovarian cancer - A prospective study. Gynecol Oncol 2007;105:145-9.
The reviewer:
Professor Jonathan Carter is Professor of Gynecological Oncology at the University of Sydney, Head of the Sydney Gynaecologic Oncology Group at the Sydney Cancer Centre and of Gynaecology Services at Royal Prince Alfred Hospital and Area Director for Gynaecological Oncology, Sydney South West Area Health Service.
Summary
Abbreviations
Cancer Antigen 125 (CA-125), Certified Gynaecological Oncologist (CGO), Fluorodeoxyglucose (FDG), Magnetic Resonance Imaging (MRI), Positron Emission Tomography/Computed Tomography (PET/CT), Risk of Malignancy Index (RMI).
Study Design
This prospective study evaluated the diagnostic value of PET/CT in the detection of a malignant ovarian tumour in patients with no previous cancer history, presenting with a pelvic mass. Patients included had RMI of >150 determined on serum CA-125, ultrasound examinations and menopausal status. RMI is a scoring system for predicting whether or not an ovarian mass is likely to be malignant (RMI score = ultrasound score x menopausal score x CA-125 level in U/ml). PET/CT was performed on 101 patients within two weeks prior to debulking/standard staging surgery; four patients chose not to undergo surgery, therefore 97 patients were included for analysis.
Findings
Ninety-one patients (94%) had an RMI >200, of which 36 (40%) had benign tumours. The sensitivity of RMI >200 in recognising a malignant tumour was 96.5% (55 of 57), while the specificity was 10% (4 of 40) (p=0.4). Median serum CA-125 level was 784U/ml (range 22-9665U/ml) among the 97 included patients.
Ninety-one patients had an exploratory laparotomy, two patients had an exploratory laparoscopy with subsequent histological examination of the tumour and four patients were pathologically diagnosed by biopsy. In 60 patients (62%), PET/CT demonstrated areas of abnormally increased metabolic activity which was considered highly suspicious for malignant tumour. In 37 patients (38%) the tumour was found to be benign. Overall, histopathology showed benign tumours in 40 of the 97 patients, and malignant tumours in the remaining 57. Seven patients were diagnosed with borderline tumours (though they were all interpreted as benign). The sensitivity and specificity of PET/CT in detecting a malignant pelvic tumour was 100% (57/57) and 92.5% (37/40) respectively (p=<0.00005).
Conclusion
The authors concluded that combined PET/CT demonstrates high diagnostic value in identifying primary ovarian cancer in patients with a pelvic mass of unknown origin and RMI >150.
Commentary
What does this article add to existing clinical evidence in this area?
There are many reasons to undertake imaging of women with suspected pelvic or adnexal masses. Clearly, the first is to confirm that indeed a mass exists, second to assess the complexity of the mass and the possibility of malignancy. Any such undertaking needs to be achievable in a cost effective manner. Such diagnostic tests need to be simple and safe to perform, relatively non-invasive with reproducible results across a wide variety of situations and pathologies, accurate and predictive and be acceptable to the patient.
Ultrasound alone has a sensitivity of between 71% and 96%. The specificity of ultrasound imaging is increased when used in a combination of ultrasound morphology, menopausal status and CA-125 level, known as the Risk of Malignancy (RMI) which achieves a high standard of accuracy, with an RMI of greater than 200 (high risk of malignancy) having a sensitivity of 80–87% and a specificity reported as 89–92%. 1,2
There is considerable evidence that while ultrasound, CT, PET and MRI are sensitive, they lack specificity in accurately excluding malignancy. PET/CT in combination has been reported to successfully detect recurrent ovarian cancer. This prospective study 3 is noted by the authors as the first to examine the value of combined PET/CT for the detection of primary ovarian cancer.
How adequate was the methodology used in addressing the aims of this study?
The study was undertaken in a University Cancer Centre over a 6–18 month period. (The abstract suggests 18 months but the text six months). One hundred and one patients were identified with a pelvic mass and a RMI >150. Histological comparisons were only available from 97 patients as four patients with PET/CT results identified as benign chose not to proceed with surgery. While consecutive patients were included, the sample may be biased as low risk patients were excluded prior to referral and after referral the study group was that with an RMI >150, although the authors note the reason given for an RMI cut-off of 150 was to ensure the inclusion of a sufficient number of patients with benign tumours.
It is unclear from the manuscript why diabetics and those with “other severe medical conditions” were excluded from the trial. The exclusion of these patients may have also biased results as false positive PET scans have been reported in diabetics and those with chronic inflammatory conditions, as the FDG biodistribution dramatically changes, with excessive uptake in normal organs and tissues.
In addition, while it is noted that the CT and PET images were evaluated by the same nuclear medicine physician and radiologist, no comment is made as to whether the PET scan physicians were blinded to the results of the original ultrasound. The vast majority of patients with ovarian cancers in the study group were also of an advanced stage (of the 42 with serous adenocarcinoma, 29 (69%) were at stage III and five had stage IV) and it seems extraordinary that simpler and less imaging would not have identified these patients.
What are the implications of this study for clinical practice in Australia?
The authors note that PET/CT may provide a better diagnostic test that would avoid unnecessary surgery in patients with benign tumours, and be able to allocate patients with malignant tumours to the appropriate specialist. However, currently in Australia once a mass is diagnosed, surgery is almost universally performed, so while a more accurate test will not reduce the need for surgery, it may influence the type or surgery performed and by whom. Masses deemed low risk would be appropriately managed by a general gynaecologist and those high-risk masses (i.e. with high risk of malignancy), should be afforded the opportunity of referral to a board certified gynaecological oncologist. When compared to general gynaecologists, surgery by a Certified Gynaecological Oncologist (CGO) has been shown to convey a significant survival advantage.
Unfortunately no information regarding cost is provided by the authors. Our own local experience is such that routine PET/CT is not available at all locations within the country. While less specific, ultrasound and CA-125 incorporated into the RMI is easily available, and will allow remote clinicians a yardstick to identify those patients most appropriate to refer for centralized care.
In the short term, the PET/CT technology should be reserved for the evaluation of spread of confirmed or suspected malignancy. Further studies are needed to determine whether there is a future role for PET/CT as a tool for staging ovarian cancer or to identify which masses may not require surgery.
References
1. Prys Davies A, Jacobs I, Woolas R, et al. The adnexal mass: benign or malignant? Evaluation of a risk of malignancy index. Br J Obstet Gynaecol 1993;100:927–31.
2. Tingulstad S, Hagen B, Skjeldestad FE, et al. The risk-of-malignancy index to evaluate potential ovarian cancers in local hospitals. Obstet Gynecol 1999;93(3):448–52.
3. Risum S, Hogdall C, Loft A, et al. The diagnostic value of PET/CT for primary ovarian cancer - A prospective study. Gynecol Oncol 2007;105:145–9.
Editor: Ms Jane Francis, Program Manager/Ovarian Cancer, National Breast Cancer Centre.
Editorial Committee: Prof Michael Friedlander – Medical Oncologist, Prof Neville Hacker – Gynaecological Oncologist, Dr Gillian Mitchell – Medical Oncologist, Dr Deborah Neesham – Gynaecological Oncologist, Ms Georgie Richter – Gynaecological Nurse, Dr Paul Dunne - Palliative Care Specialist.
Disclaimer
Clinical Update - Ovarian Cancer is produced by the National Breast Cancer Centre (NBCC) and is intended to provide health professionals with timely expert commentary on new research in ovarian cancer. Commentaries included in Clinical Update - Ovarian Cancer do not replace recommendations included in NBCC clinical practice guidelines.
Information contained in Clinical Update - Ovarian Cancer is not intended to be used as substitute for an independent health professional's advice. The NBCC does not accept any liability for any injury, loss or damage incurred by use of or reliance on the information contained in Clinical Update - Ovarian Cancer. The NBCC develops material based on the best available evidence however cannot guarantee and assumes no legal liability or responsibility for the currency or completeness of the information.
