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Ovarian cancer staging and follow-up

Rosemarie 
Forstner
17 June, 2011  

Dr Rosemarie 
Forstner MD
Department of radiology, Landeskliniken Salzburg, Paracelsus Medical University, Salzburg, Austria

On behalf of the European Society of Urogenital Radiology’s (ESUR’s) female imaging subcommittee

These guidelines were established as a result of the continuous innovations in diagnosis and treatment and new aspects of interdisciplinary co-operation in treating patients suffering from cancer. This co-operation is evinced by multidisciplinary cancer conferences that are the hallmark of high-quality cancer management and have been established in many oncology centres.

In ovarian cancer, which continues to pose a challenge, radiology plays a key role in the selection of patients for cytoreductive surgery versus neo-adjuvant chemotherapy through its ability in optimising the surgical approach, in defining indications for and planning image-guided biopsy and in assessing tumour relapse.

The European Society of Urogenital Radiology’s (ESUR) female imaging subcommittee has established imaging guidelines for staging gynaecologic cancers.1 These guidelines should assist the radiologist as a framework in multidisciplinary conference and, in the following article, the recently published guidelines for ovarian cancer staging and follow-up are summarised.2 They are based on the review of literature and consensus of 12 European experts in gynaecological radiology and thus they present a consensus throughout Europe.

Staging patients with suspected ovarian cancer
Goals of pre-operative staging and imaging modalities. Sonography (ultrasound) is the first-line imaging modality in assessing patients with a suspected adnexal mass. It is the modality of choice for defining proper management and further investigations.

In general, based on clinical and sonographical findings and levels of the tumour marker CA-125, adnexal masses fall into one of these categories:

  • 
Benign lesions that are usually managed on the basis of symptoms
  • 
Indeterminate adnexal lesions where magnetic resonance imaging (MRI) is suggested as problem-solving modality3
  • 
Sonographically malignant masses with or without signs of peritoneal metastases.

Only for the latter is preoperative staging recommended.

The goals of pre-operative staging in suspected ovarian cancer are:

  • 
Confirmation of the sonographically malignant adnexal mass
  • 
Assessment of tumour burden, mapping of the distribution of metastatic disease and diagnosis of possible complications e.g. bowel obstruction, hydronephrosis or venous thrombosis
  • 
Exclusion of a primary site in the gastrointestinal tract, breast or pancreas whose metastatic spread might mimic primary ovarian cancer.

This information will allow us to design an individualised therapeutic strategy, which is optimally the result of a multidisciplinary consensus.4 It is recommended that each multidisciplinary team has a clear investigation algorithm.

Contrast-enhanced computed tomography (CT) with coverage from the base of the lungs to the inguinal region is recommended as the imaging technique of choice for pre-operative staging. The main reason is the fact that this technique delivers all relevant information in a short examination time (Figure 1).

Although MRI5,6 performs as well as CT, MRI is only recommended as second-line imaging modality and should only replace staging by CT in young patients due to issues of radiation dose and in cases of contraindication of CT. Contraindications include such things as contrast media intolerance, renal insufficiency and pregnancy. If MRI is performed for staging, then diffusion-weighted magnetic resonance imaging (DW-MRI), a new MRI technique, should be included in the imaging protocol to better assess peritoneal dissemination.

Sonography does not provide sufficient information for exact pre-operative mapping, as assessment of metastatic implants in the upper abdomen and lymph nodes is inferior compared to CT or MRI.5,6

Intravenous urography (IVU) and gastro-intestinal (GI) studies should not be performed anymore, as this diagnostic information is delivered by cross-sectional imaging. In instances of suspected bladder or rectosigmoid invasion, histologic confirmation by cystoscopy and endoscopy respectively is employed.

The additional benefit of positron emission tomography CT (PET/CT) over CT alone in pre-operative staging of ovarian cancer is not yet fully established.7 PET/CT can be used for staging of ovarian cancer alternatively to MRI as a second-line staging modality. It may also be indicated in suspected stage IV disease and as a problem-solving modality in indeterminate lymph nodes.

Radiological reporting. Management of ovarian cancer is closely related to cancer stage and to the patient’s clinical medical performance. This is why pre-operative imaging should provide comprehensive information about the primary tumour and its dissemination, including tumour burden, relevant sites of spread and other details useful for surgery planning.  

There was consensus that this is optimally provided only in form of a structured radiological report. The report should include a statement of the FIGO/TNM classification, as with imaging, but also requires a detailed summary of elements necessary for surgery planning and treatment regimen decision. Such a structured report should include size, site and morphology of the ovarian mass.

The need for other surgical experts/disciplines to assist may be required in case of invasion of sites, such as bladder, bowel or pelvic sidewall. This is also the case in bowel obstruction, hydronephrosis or venous obstruction/thrombosis. Site and amount of ascites and pleural effusion should be reported. In the latter, cytologic analysis of the pleural fluid will be necessary.

Omental metastases and size and site of peritoneal/serosal implants outside the pelvis with size less or larger than 2cm should be reported, as they serve as a roadmap for surgery planning and help in the selection of sites for biopsies. Lymph nodes should be described using a cut-off of the short axis diameter of 1cm, or clusters of smaller lymph nodes in the pelvis and abdomen, and with 5mm of diameter in a costophrenic location. Reporting according to the response evaluation criteria in solid tumours (RECIST) is currently only warranted in case of clinical trials.8

Cytoreductive surgery versus neo-adjuvant chemotherapy. The gold standard of primary treatment of ovarian cancer is surgery with adjuvant chemotherapy in the majority of cases. Surgery includes a comprehensive staging laparotomy with total abdominal hysterectomy, bilateral salpingo-oophorectomy, infracolic omentectomy and lymphadenectomy.

Furthermore, peritoneal cytology and multiple peritoneal biopsies are obtained throughout the pelvis and upper abdomen. During this procedure, cytoreduction (‘debulking’) of all tumour deposits is attempted with the aim of removing all macroscopic tumours in the pelvis and throughout the abdomen. Tumour debulking is generally considered successful or optimal when no residual tumour larger than 1cm–2cm is left after the initial staging laparotomy, as only in these patients has a significant benefit in terms of response to chemotherapy and survival been reported.9

Alternatively, neo-adjuvant chemotherapy has emerged as a treatment option in patients with advanced ovarian cancer, including patients with medical comorbidities, high risk of surgery, stage IV disease, or extensive tumour load.10

CT and MRI have shown excellent performance in the prediction of ‘non-optimally resectable’ disease in patients with ovarian cancer.11 Identification of ‘non-optimally resectable disease’ may help to select candidates in whom chemotherapy seems the most appropriate therapy. However, it is important to realise that these criteria may vary and depend on the medical condition of the patient, surgical risks and on the aggressiveness of the oncological surgeon and, therefore, they can only be used as a basis for a multidisciplinary consensus.

Image-guided biopsy. Multidisciplinary discussion should also determine the need for image-guided biopsy. This technique can be performed with ultrasound or CT and should replace laparoscopy in patients with peritoneal carcinomatosis, if this technique is only performed with the intention to obtain histology.

Image-guided biopsy is a safe, minimally invasive radiological procedure that provides histology and requires only local anaesthesia. Indications include the histological proof before neo-adjuvant chemotherapy for ovarian cancer, and uncertainty about the aetiology of peritoneal metastases to exclude other primaries with such a pattern of dissemination.12   

Staging patients treated for ovarian cancer
The combination of clinical assessment and CA-125 measurement is routinely used to monitor patient treated for ovarian cancer.13 Rising CA-125 levels may, however, precede clinical recurrence with a median lead time of 3–5 months. For suspected recurrence, CT remains the mainstay of imaging. The reasons are that CT is reproducible, widely available and well understood.

Optimally, a baseline CT after cytoreductive surgery is performed that will ensure reproducibility of the results for future comparison. CT is used to evaluate treatment response to chemotherapy including those patients treated with neo-adjuvant therapy prior to interval debulking surgery, to assess suspected relapse in rising CA-125 levels or clinical suspicious symptoms.

PET/CT is emerging as the optimal imaging technique for suspected recurrence in ovarian cancer, particularly with negative CT or MRI. MRI is reserved as a problem-solving modality to assess indeterminate masses on CT or before surgical resection of pelvic recurrence.14

References

  1. 
Kinkel K et al. European Radiolgy 2009;19:1565-1574.
  2. 
Forstner R. et al. European Radiology 2010, Epub ahead of print.
  3. 
Spencer JA et al. European Radiology 2010; 20:25-35.
  4. 
Spencer JA. BJR 2005;78:S94-S10.
  5. Tempany CM et al. Radiology 2000;215:761-767.
  6. 
Kurtz AB et al. Radiology 1999;212:19-27.
  7. 
Kitajima K et al. Eur J Nucl Med Mol Imaging 2008;35:1912-1920.
  8. 
Eisenhauer E et al. European Journal of Cancer 2009;45:228-247.
  9. 
Bristow RE et al. Clin Oncol 2002;20:1248-1259.
  10. 
Chi DS et al. Gynecologic Oncology 2008;11:391-399.
  11. 
Quayyum A et al. Gynecol Oncol 2005;96:301-306.
  12. 
Griffin N et al. Eur Radiol 2009;19:230-235.
  13. 
Gaducci A et al. Crit Rev Oncol/Hematol 2009;71:43-52.
  14. Gu P et al. Eur J Radiol 2009;71:164-174.