A study to find out if a new blood test (microRNA) can be used to monitor people after surgery for seminoma or dysgerminoma cancer

ISRCTN	ISRCTN92524070
DOI	https://doi.org/10.1186/ISRCTN92524070
Integrated Research Application System (IRAS)	342479
Central Portfolio Management System (CPMS)	61831
CRUK Grant code	24/008
Sponsor	Institute of Cancer Research
Funder	Cancer Research UK

Submission date: 22/12/2025
Registration date: 14/01/2026
Last edited: 14/01/2026

Recruitment status: Not yet recruiting
Overall study status: Ongoing
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
This study wants to find out if a blood test that detects circulating microRNA (miRNA) could be used to detect if a patient’s cancer has returned. Testicular seminoma is one of the commonest cancers in young men, while ovarian dysgerminoma is rarer, typically affecting teenagers/young adults. Stage I disease is well managed with surgery followed by surveillance using imaging (CT or MRI, or ultrasound for younger dysgerminoma patients), but this is a burden for patients, may expose them to harmful radiation, and is costly for the NHS. Approximately 15% of these patients will have their cancer come back, and this is usually treated successfully. miRNA shows significant promise as a blood-based marker for detecting if a patient’s cancer is returning. It might reduce the need for imaging and even bring relapse detection forward, reducing the need for subsequent intensive treatment.

Who can participate?
OTIS-S is split into two parts. OTIS-S aims to recruit people with early (stage I) seminoma or dysgerminoma who have undergone surgery and are planned for surveillance.

What does the study involve?
In part A, participants who join OTIS-S will have their blood analysed to see if any miRNA can be detected, alongside the regular imaging they would have as standard of care. Once the trial has enough data and the study team are satisfied with the results, the study will move on to part B, where patients will have either miRNA blood tests only or imaging only.

Part A is expected to take 2.5 years to enrol 260 participants; all participants will be followed up for 5 years after they are enrolled. The results from Part A of the study will be used to develop the next part (Part B) of the study. Part B is expected to recruit for approximately 3.5 years; participants in Part B will be followed up for 3 years after they are enrolled.

What are the possible benefits and risks of participating?
For the majority of patients, there are no direct benefits to taking part, but the information gained from this study will help improve treatment for other people with seminoma in the future. It is possible that the miRNA testing will help to pick up the cancer returning earlier, but it is unknown if that will be the case.

People taking part in this study will have CT or MRI scans. They may also have a PET-CT scan and an X-ray. They will still have most, if not all, of these if they do not take part. CT scans, PET-CT scans and X-rays use ionising radiation to form images of the body, which provide doctors with clinical information. Ionising radiation can cause cell damage that may, after many years or decades, turn cancerous. The chances of this happening to you as a consequence of taking part in this study are 0.1%. There are no other anticipated disadvantages or risks involved in taking part in this study, as people will receive the usual care.

Where is the study run from?
NHS hospitals across the UK, coordinated by the Institute of Cancer Research Clinical Trials and Statistics Unit (ICR-CTSU).

When is the study starting and how long is it expected to run for?
March 2026 to March 2025. Part A of the study is due to start enroling participants in March 2026. Part B is expected to start enroling in Autumn 2028.

Who is funding the study?
The Cancer Research UK.

Who is the main contact?
OTIS-S-icrctsu@icr.ac.uk

Contact information

Deborah Gardiner
Public, Scientific

Study contact
ICR Clinical Trials & Statistics Unit (ICR-CTSU)
ICR/RM Centre for Trials & Population Data Science
The Institute of Cancer Research
Brookes Lawley Building
32 Oakleaf Avenue
London
SM2 5GP
United Kingdom

Phone	+442087224057
Email	otis-s-icrctsu@icr.ac.uk

Dr Alison Reid
Principal investigator

Chief Investigator, The Royal Marsden NHS Foundation Trust
Downs Road
Sutton
SM2 5PT
United Kingdom

ORCID ID	0000-0001-8567-4941
Phone	+44 020 8 642 6011 ext. 4319
Email	Alison.Reid@rmh.nhs.uk

Study information

Primary study design	Interventional
Allocation	Randomized controlled trial
Masking	Open (masking not used)
Control	Active
Assignment	Sequential
Purpose	Screening
Scientific title	A phase II/III trial evaluating use of circulating serum miRNA as part of active surveillance for patients with stage I seminoma and dysgerminoma
Study acronym	OTIS - S
Study objectives	Primary Objective Part A: • To demonstrate the high sensitivity of miRNA for relapse detection in patients who have undergone surgery for stage I seminoma or dysgerminoma Part B: • To demonstrate the non-inferiority of miRNA monitoring, when compared with standard imaging, for the detection of advanced relapse in patients who have undergone surgery for stage I seminoma or dysgerminoma Secondary Objectives Part A: • To demonstrate the high specificity of miRNA for relapse detection in this setting • To demonstrate the feasibility and acceptability to patients of miRNA monitoring in this setting • To quantify the lead time (extent to which relapse diagnosis can be brought forward) associated with miRNA monitoring when compared with standard surveillance Part B: • To demonstrate the cost-effectiveness of miRNA monitoring compared with standard surveillance • To demonstrate reduced use of imaging and subsequent impact on radiation exposure with miRNA monitoring compared with standard imaging-based surveillance • To further evaluate the acceptability to patients of miRNA monitoring in this setting • To quantify anxiety, fear of recurrence and health-related quality of life for patients managed with the two different approaches to surveillance • To understand any impact on disease outcomes and subsequent treatment associated with the use of miRNA monitoring in place of standard imaging • To understand the risk-benefit balance of a miRNA monitoring approach (when compared to standard surveillance) from the perspective of different stakeholders, including patients
Ethics approval(s)	Approved 19/12/2025, London - South East Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; -; londonsoutheast.rec@hra.nhs.uk), ref: 25/LO/0836
Health condition(s) or problem(s) studied	Seminoma and dysgerminoma
Intervention	OTIS-S will include patients with stage I seminoma or dysgerminoma and will use a seamless, phased approach to evaluation. In part A (single-arm), 260 patients will undergo regular miRNA testing alongside standard active surveillance (including imaging) and sensitivity will be assessed. If sensitivity is sufficiently high, part B will randomise 558 patients to miRNA monitoring (with only triggered imaging) vs standard active surveillance. Patient pathway Participants will be recruited from selected sites across the UK. Potential participants will be identified in oncology clinics and discussed at Multi-Disciplinary Team (MDT) meetings. Participants will be those with stage I seminoma or dysgerminoma who have had surgery and have no adjuvant therapy planned. Participants will be approached by a member of their clinical care team and will receive a verbal explanation of the trial, together with a Patient Information Sheet, which they will take home with them. They will be given sufficient time to make a decision about whether they would like to participate and will be able to discuss their options with friends, family or their GP. They will have the opportunity to raise any questions about OTIS-S with their clinical care or research team and these will be addressed prior to their decision about whether to participate. Should they choose to participate, they will be asked to sign a consent form to record their informed consent. Consent will be sought from the parent/guardian for potential participants under 16. Young people will be involved in the decision as much as possible and offered the opportunity to assent as appropriate. Part A participants: In Part A, all registered OTIS-S participants will undergo serum miRNA monitoring alongside standard surveillance using MRI/CT. The participants will undergo the following assessments: Assessments after registration: Medical history Physical examination Routine Tumour Markers: AFP, HCG and LDH (investigations undertaken as part of standard care within 3 weeks prior to registration are acceptable) Radiological assessment as follows (investigations undertaken as part of standard care within 6 weeks prior to registration are acceptable): o For seminoma participants: MRI/CT abdomen as per local practice o For dysgerminoma participants: MRI and/or abdominal ultrasound. Collection of blood sample for miRNA analysis Follow-up surveillance assessments: At 3 months (m), 6m, 9m, 12m, 15m, 18m, 21m, 24m, 30m, 36m, 42m, 48m, 54m and 60m after registration in the trial Physical examination Routine tumour Markers (AFP, B-HCG and LDH) Review/reporting SAEs as appropriate Collection of blood sample for miRNA analysis (except at 54m) Imaging assessments: o For seminoma participants: Cross-sectional abdominal imaging at 6m, 18m and 36m, preferably with MRI but CT can be used according to local practice. o For dysgerminoma participants: Cross-sectional abdominal+/-pelvic imaging at 6, 18 and 36 months, preferably with MRI. For participants under the age of 19, pelvic ultrasound (US) may be used at the physician's discretion, where MRI is not possible or where US is used routinely at the site. Additional imaging according to local practice: In addition to the required radiological assessments above, the following can also be performed according to local practice: o cross-sectional imaging (abdominal+/-pelvic MRI or CT) can be performed at up to 4 further time points over the 5-year follow-up period o For seminoma, chest x-ray can be performed as per local practice o For dysgerminoma participants, low-dose chest CT and transvaginal US can be performed as per local practice. Acceptability questionnaire to be completed by participant at 12m (participants aged 16 and over only) Follow-up in response to specific miRNA analysis results: If a participant has a miRNA result that is indeterminate, then a physical examination, routine tumour markers and another blood collection for miRNA analysis will be performed six weeks after the indeterminate result. If a participant has a positive miRNA result, the participant will undergo an MRI/CT (as per local practice). For participants under the age of 19, US may be used at the physician's discretion. A repeat miRNA test will also be performed. In the event of negative imaging but a further positive miRNA result, the participant will undergo an FDG PET CT (and contralateral US of the testis for seminoma participants). If the participant has disease recurrence confirmed, they will receive relapse treatment/management as per standard of care. Part B participants: All part B participants will be randomised to receive either monitoring via the miRNA blood test or imaging only. The assessments for part B participants will be similar to part A participants, with the exception that the imaging-only groups will not have miRNA blood samples taken and the miRNA-only group will not have standard imaging except in the case of a positive miRNA result. For the part B participants having miRNA blood samples taken, it is intended that this will only be done at randomisation and 3, 6, 12, 18, 24, 30 and 36 months post-randomisation. Prior to the commencement of Part B, a protocol amendment will be issued where full details of Part B assessments will be confirmed. It is intended that recruitment to part A will take 2.5 years and recruitment to part B will take 3.5 years. All patients will be followed up for 5 years after trial entry. Central trial management will be conducted by the Institute of Cancer Research Clinical Trials and Statistics Unit (ICR-CTSU). Analysis of all primary and secondary endpoints will be conducted by ICR-CTSU and will be pre-specified in a detailed analysis plan. Primary analysis of Part A will be based on the number of relapses observed but is expected to take place around the time of completing recruitment to Part A, thus allowing a relatively seamless transition into Part B. Further secondary analysis of part A data will take place as participants proceed through the follow-up period. Part B analysis is expected to take place after all patients have been followed up for 3 years. A Trial Management Group (TMG) will be set up and will have responsibility for the day-to-day management of the trial. It will include the Chief Investigator, ICR-CTSU methodology lead, co-investigators and identified collaborators, the Trial Statistician and the Trial Manager. Principal Investigators and key study personnel will be invited to join the TMG as appropriate to ensure representation from a range of sites and professional groups and will also include lay/consumer representatives. An independent Trial Steering Committee (TSC) and Independent Data Monitoring Committee (IDMC) will be established, including people with relevant clinical and methodological expertise. The TSC will meet annually throughout the trial to oversee the study's progress on behalf of the sponsor and funder. The IDMC will meet in confidence, at least annually, to review data and make recommendations to the TSC and TMG.
Intervention type	Other
Primary outcome measure(s)	Sensitivity of miRNA for relapse detection measured using the number of relapses detectable on miRNA testing before or at the same time as detection on imaging (or via other components of standard surveillance), as a proportion of the total number of relapses identified via standard investigations, at registration, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54 and 60 months post registration
Key secondary outcome measure(s)	Lead time for relapse detection on miRNA measured using the time between relapse detection on miRNA (date sample taken) and relapse detection on imaging (date of scan) at registration, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54 and 60 months post registration Specificity of miRNA for relapse detection measured using the number of non-relapsing participants (based on imaging) whose miRNA levels remained negative (or indeterminate) throughout the follow-up period, as a proportion of all non-relapsing participants, at registration, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54 and 60 months post registration Time from blood draw for miRNA testing to miRNA results being available to the clinical team (and participant), and the number (proportion) of results available within 2 weeks measured using data collected during the study at 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54 and 60 months post registration Adherence to miRNA testing measured using the number of samples taken for miRNA testing as a proportion of all scheduled tests, the number of tests performed more than a 4-week window either side of the schedule time point and the number of samples that could not be analysed, at registration, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54 and 60 months post registration Adherence to imaging schedules measured using the number of attendances for imaging as a proportion of all scheduled imaging; the number of scans performed; numbers of scans performed more than a 4-week window either side of the schedule time point will also be reported at registration, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54 and 60 months post registration Patient-reported acceptability of miRNA monitoring without routine surveillance imaging measured using a trial-specific questionnaire based on a validated, generic instrument for evaluating acceptability of healthcare interventions at 12 months post registration
Completion date	15/03/2035

Eligibility

Participant type(s)	Patient
Age group	All
Lower age limit	0 Years
Upper age limit	110 Years
Sex	All
Target sample size at registration	818
Key inclusion criteria	1. Histologically confirmed testicular pure seminoma* or extra-cranial dysgerminoma 2. Primary cancer managed by orchiectomy or complete surgical removal of dysgerminoma (trial entry is permitted within 8 weeks following surgery, up to a maximum of 10 weeks under exceptional circumstances.) 3. Stage I based on CT or MRI abdomen and pelvis and CT chest. For participants under the age of 19, pelvic ultrasound (US) may be used at physician’s discretion where MRI is not possible or where US is used routinely at site. 4. Normal post-operative tumour markers as follows (may have been raised pre-operatively and immediately post-operatively, but have returned to normal range): a.AFP< = 10 ng/ml [AFP > 10 and < = 25 ng/ml and confirmed as not rising on three successive tests may be accepted as eligible after discussion with Chief Investigator or delegate] b.β-HCG< = 4 IU/L c.LDH< 1.2 x upper limit of normal 5. No adjuvant therapy planned 6. Participant (or, where the participant is under 16 years old, their parent or guardian) has given written informed consent prior to any study-specific procedures. *Patients with any non-seminomatous elements, including teratoma, are not eligible
Key exclusion criteria	1. Previous contralateral testis tumour within 3 years of trial entry. 2. Previous or concurrent illness or condition which, in the investigator’s opinion, would interfere with participation in the trial 3. Pregnancy (pregnancy can be excluded on the basis of β-HCG result) 4. Unable/unwilling to comply with trial visit schedule/trial assessments.
Date of first enrolment	15/03/2026
Date of final enrolment	15/03/2032

Locations

Countries of recruitment

United Kingdom
England
Northern Ireland
Scotland
Wales

Study participating centres

St James' S University Hospital

Beckett Street
Leeds
LS9 7TF
England

Worthing Hospital

Lyndhurst Road
Worthing
BN11 2DH
England

Northern General Hospital

Herries Road
Sheffield
S5 7AU
England

The Royal Marsden Hospital

Fulham Road
London
SW3 6JJ
England

Leicester Royal Infirmary

Infirmary Square
Leicester
LE1 5WW
England

Velindre NHS Trust

Unit 2
Charnwood Court
Heol Billingsley
Cardiff
CF15 7QZ
Wales

Southampton General Hospital

Tremona Road
Southampton
SO16 6YD
England

University Hospitals Bristol and Weston NHS Foundation Trust

Trust Headquarters
Marlborough Street
Bristol
BS1 3NU
England

Queen Elizabeth Hospital

Mindelsohn Way
Edgbaston
Birmingham
B15 2GW
England

Queens Medical Centre

Nottingham University Hospital
Derby Road
Nottingham
NG7 2UH
England

Lothian

Waverleygate
2-4 Waterloo PLACE
Edinburgh
City of Edinburgh
EH1 3EG
Scotland

Poole Hospital

Longfleet Road
Poole
BH15 2JB
England

Maidstone Hospital

Hermitage Lane
Maidstone
ME16 9QQ
England

Royal Preston Hospital

Sharoe Green Lane
Fulwood
Preston
PR2 9HT
England

Tonna Hospital

Tonna Uchaf
Tonna
Neath
SA11 3LX
Wales

Colchester General Hospital

Turner Road
Colchester
CO4 5JL
England

Grampian

Summerfield House
2 Eday Road
Aberdeen
AB15 6RE
Scotland

Birmingham Women's and Children's NHS Foundation Trust

Steelhouse Lane
Birmingham
B4 6NH
England

Belfast Health and Social Care Trust

Trust Headquarters
A Floor - Belfast City Hospital
Lisburn Road
Belfast
BT9 7AB
England

Royal Preston Hospital

Sharoe Green Lane
Fulwood
Preston
PR2 9HT
England

Westmorland General Hospital

Burton Road
Kendal
LA9 7RG
England

Cambridge University Hospitals NHS Foundation Trust

Cambridge Biomedical Campus
Hills Road
Cambridge
CB2 0QQ
England

Royal Surrey County Hospital Guildford

Egerton Road
Guildford
GU2 7XX
England

John Radcliffe Hospital

Headley Way
Headington
Oxford
OX3 9DU
England

University College London Hospital

250 Euston Road
London
NW1 2PG
England

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available upon request from Otis-s-icrctsu@icr.ac.uk. The ICR-CTSU supports the wider dissemination of information from its research and increased cooperation between investigators. Trial data are collected, managed, stored, shared, and archived according to ICR-CTSU Standard Operating Procedures to ensure the enduring quality, integrity, and utility of the data. Formal requests for data sharing are considered in line with ICR-CTSU procedures, with due regard given to funder and sponsor guidelines. Requests are via a standard proforma describing the nature of the proposed research and the extent of data requirements. Data recipients are required to enter a formal data sharing agreement that describes the conditions for release and requirements for data transfer, storage, archiving, publication, and intellectual property. Requests are reviewed by the Trial Management Group (TMG) in terms of scientific merit and ethical considerations, including patient consent. Data sharing is undertaken if proposed projects have a sound scientific or patient benefit rationale, as agreed by the TMG and approved by the Independent Data Monitoring and Steering Committee, as required. Restrictions relating to patient confidentiality and consent will be limited by aggregating and anonymising identifiable patient data. Additionally, all indirect identifiers that could lead to deductive disclosures will be removed in line with Cancer Research UK Data Sharing Guidelines. Full details of the ICR-CTSU data sharing policy are available at https://www.icr.ac.uk/research-and-discoveries/centres-and-strategic-collaborations/clinical-trials-and-statistics-unit-icr-ctsu/about-us/data-sharing.

Editorial Notes

22/12/2025: Trial's existence confirmed by the National Institute for Health and Care Research (NIHR) (UK).