Localising occult prostate cancer metastasis with advanced imaging techniques (LOCATE trial): a prospective cohort, observational diagnostic accuracy trial investigating whole-body magnetic resonance imaging in radio-recurrent prostate cancer

Sola Adeleke, Arash Latifoltojar, Harbir Sidhu, Myria Galazi, Taimur T Shah, Joey Clemente, Reena Davda, Heather Ann Payne, Manil D Chouhan, Maria Lioumi, Sue Chua, Alex Freeman, Manuel Rodriguez-Justo, Anthony Coolen, Sachin Vadgama, Steve Morris, Gary J Cook, Jamshed Bomanji, Manit Arya, Simon Chowdhury, Simon Wan, Athar Haroon, Tony Ng, Hashim Uddin Ahmed, Shonit Punwani, Sola Adeleke, Arash Latifoltojar, Harbir Sidhu, Myria Galazi, Taimur T Shah, Joey Clemente, Reena Davda, Heather Ann Payne, Manil D Chouhan, Maria Lioumi, Sue Chua, Alex Freeman, Manuel Rodriguez-Justo, Anthony Coolen, Sachin Vadgama, Steve Morris, Gary J Cook, Jamshed Bomanji, Manit Arya, Simon Chowdhury, Simon Wan, Athar Haroon, Tony Ng, Hashim Uddin Ahmed, Shonit Punwani

Abstract

Background: Accurate whole-body staging following biochemical relapse in prostate cancer is vital in determining the optimum disease management. Current imaging guidelines recommend various imaging platforms such as computed tomography (CT), Technetium 99 m (99mTc) bone scan and 18F-choline and recently 68Ga-PSMA positron emission tomography (PET) for the evaluation of the extent of disease. Such approach requires multiple hospital attendances and can be time and resource intensive. Recently, whole-body magnetic resonance imaging (WB-MRI) has been used in a single visit scanning session for several malignancies, including prostate cancer, with promising results, providing similar accuracy compared to the combined conventional imaging techniques. The LOCATE trial aims to investigate the application of WB-MRI for re-staging of patients with biochemical relapse (BCR) following external beam radiotherapy and brachytherapy in patients with prostate cancer.

Methods/design: The LOCATE trial is a prospective cohort, multi-centre, non-randomised, diagnostic accuracy study comparing WB-MRI and conventional imaging. Eligible patients will undergo WB-MRI in addition to conventional imaging investigations at the time of BCR and will be asked to attend a second WB-MRI exam, 12-months following the initial scan. WB-MRI results will be compared to an enhanced reference standard comprising all the initial, follow-up imaging and non-imaging investigations. The diagnostic performance (sensitivity and specificity analysis) of WB-MRI for re-staging of BCR will be investigated against the enhanced reference standard on a per-patient basis. An economic analysis of WB-MRI compared to conventional imaging pathways will be performed to inform the cost-effectiveness of the WB-MRI imaging pathway. Additionally, an exploratory sub-study will be performed on blood samples and exosome-derived human epidermal growth factor receptor (HER) dimer measurements will be taken to investigate its significance in this cohort.

Discussion: The LOCATE trial will compare WB-MRI versus the conventional imaging pathway including its cost-effectiveness, therefore informing the most accurate and efficient imaging pathway.

Trial registration: LOCATE trial was registered on ClinicalTrial.gov on 18th of October 2016 with registration reference number NCT02935816.

Keywords: Brachytherapy; Cost comparison; Cost-effectiveness; Economic evaluation; Magnetic resonance imaging; Positron emission tomography; Prostate cancer; Radiotherapy; Recurrence.

Conflict of interest statement

The study has not received any funding/assistance from a commercial organisation. The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Trial flowchart. The trial flowchart describing the standard of care pathway through which patients were reviewed and clinical decisions made. A parallel research pathway was designed to mimic the standard pathway without interfering in patient care except when clinically significant incidental findings are identified
Fig. 2
Fig. 2
Enhanced reference standard derivation flowchart. FN: False Negative, TP: True Positive, FP: False Positive, TN: True Negative, UK: Unknown, ADT: Androgen Deprivation Therapy

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