ROCkeTS

 

ROCkeTS-LogoROCkeTS is a diagnostic test accuracy study that aims to identify, refine and validate tests and clinical risk scores (risk prediction models) that estimate the probability of having ovarian cancer in post and premenopausal women with symptoms.

The  phase 3 prospective study is open to recruitment in the UK.


Background

 

We know that lots of women have symptoms such as bloating and tummy discomfort. It is also very common to have cysts (balloon like swellings) on women’s ovaries picked up by ultrasound. A very small proportion of these women will go on to be diagnosed with ovarian cancer. The purpose of this study is to identify better tests for ovarian cancer. This may help us to diagnose more women with ovarian cancer early but also reduce unnecessary tests, hospital visits and distress in women who don’t have cancer.

 National Institute for Health and Care Excellence (NICE), which is the body that establishes standards of care in the UK has issued guidelines to GP’s, to test women if they have symptoms of bloating/tummy discomfort with a blood test called CA125 and then a pelvic ultrasound if the CA125 test result is abnormal. However a published survey of 258 GP’s and a hospital audit suggest that GPs refer patients if they have symptoms or if either test is abnormal.

 In fact the blood test CA125 can be raised in lots of other innocent conditions e.g. during menstrual periods. Also in younger women, non-cancerous cysts on the ovary are in fact very common. Conversely CA125 is only raised in half the women with early ovarian cancer. This means that many women are referred who actually have a very low risk of cancer, and others are not referred until their cancer has reached a more advanced stage.

 Ovarian cancer affects 6500 women each year. Commonly 8 out of 10 women are diagnosed at an advanced stage of cancer, and have to undergo extensive surgery and chemotherapy. By identifying better tests for ovarian cancer, we may be able to diagnose more women with ovarian cancer early when they have a better chance of responding to treatment. We also know that women with ovarian cancer who are referred for thorough surgery by a gynaecological cancer specialist have the best outcomes, so this study may develop improved testing in hospital after referral to help to identify the patients who will need this. Equally, if we can clearly identify the women who have innocent cysts then they can be spared surgery or undergo surgery through key hole.

 

The Study Team

      • Sudha Sundar, University of Birmingham, Chief Investigator.
      • Prof Sean Kehoe, University of Birmingham.
      • Prof Jon Deeks, Biostatistics, University of Birmingham.
      • Dr Clare Davenport, University of Birmingham
      • Dr Susan Mallett, Biostatistics, University of Birmingham
      • Dr Caroline Rick, Birmingham Clinical Trials Unit.
      • Prof Richard Neal, GP, North Wales Primary Care, Bangor University.
      • UCL - Prof Usha Menon, Dr Aleksandra Gentry-Maharaj and Dr Mathew Burnell, UCL).
      • IOTA group - Prof Dirk Timmerman, Prof Ben Van Calster, University of Leuven, Prof Tom Bourne, Imperial and University of Leuven.
      • Hilary Stobart, patient representative.

Design

ROCkeTS has multiple phases or work packages that all start simultaneously

The project will be conducted in 4 interlinked phases

  • Phase 1- Systematic reviews of literature
  • Phase 2 – Interrogation of datasets/samples from UKOPS, UKCTOCS and IOTA to refine model using tests identified in Phase 1
  • Phase 3 – Prospective study to validate new models
  • Phase 4 – Analysis and Pathways generation

Aim of Study

To identify, refine and validate tests and clinical risk scores (risk predicition models) that estimate the probability of having ovarian cancer for both post and premenopausal women.

To identify optimal risk thresholds for the models that can guide patient management

Setting for phase 3 prospective study

We recruit women aged 16-90 presenting to:

Outpatient clinics, 2 week urgent referrals, inpatient and emergency referrals to secondary care

Target Population

Pre and Postmenopausal women between the age of 16 and 90 years with symptoms of suspected OC.

Inclusion criteria for pre and postmenopausal women:

  • Women referred with symptoms of suspected OC (typical referral symptoms are defined in section 2.5 of the protocol). 
  • Aged between 16 and 90 years. Both pre and postmenopausal are included.
  • In addition women must have test results from one of the following;
  1. A raised Ca125 test result (even if imaging has not been done yet)
  2. Abnormal imaging result showing a lesion (even if CA125 test is not raised).
  3. Both a raised CA125 test and an abnormal imaging result showing a lesion
  •  Patients able to provide informed consent.

Additional inclusion criteria for PREmenopausal women:

  • All above inclusion criteria AND must be scheduled to undergo surgery/biopsy for suspected OC or adnexal mass.

Exclusion criteria for pre and postmenopausal women:

  • USG reveals simple ovarian cysts < 5cm in size (very low risk of malignancy) and patient does not have a raised CA125.
  • Patients who are pregnant.
  • Previous ovarian malignancy.
  • Active non ovarian malignancy – Women with a past history of cancer are only eligible if there are no documented persistent or recurrent disease and have not received treatment for this in the last 12 months. This exclusion does not apply to patients with premalignant disease e.g. cervical intra-epithelial neoplasia or patients receiving Tamoxifen/other drugs to prevent breast cancer recurrence.

Additional exclusion criteria for POSTmenopausal women:

  • Patients who decline transvaginal scan.

 

Intervention

 

All women participating in the study complete a symptom questionnaire, donate a blood sample and undergo a transvaginal ultrasound (internal scan) by specially trained sonographers or doctors.

As part of this study, sonographers and doctors across 17 hospital trusts in the UK have received specialist ultrasound training by international experts belonging to the ‘International ovarian tumour analysis’  (IOTA) team and have been certified to conduct this. These sonographers and doctors will record additional features on the scan that may be helpful in making a correct diagnosis of ovarian cyst or cancer. 

Doctors treating women participating in the study will have access to the scan information but not the blood test as the blood will not be analysed in batches at a later date.

Participants will receive the usual care that their doctor has planned for them.

Outputs

At the end of the project, we will establish best tests and pathways for primary care and secondary care for the diagnosis of ovarian cancer in women with symptoms.

We will identify the costs associated with the best pathways and conduct a ‘cost consequence’ analysis

An online training module for IOTA ultrasound will be available for use in the NHS.

The ROCkeTS study is funded by the National Institute for Health Research nihr_colour