Exploiting Risk-Based Risk Stratification in Early Prostate Cancer to Discriminate Progressors From Non-Progressors (RECONCILE)

This study seeks to analyse MRI images and biological samples from 60 men diagnosed as having intermediate risk prostate cancer at baseline and one year afterwards to compare the molecular, genetic and transcriptomic differences between cancers that progress and cancers which do not.

Study Overview

• Status: Active, not recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Other: NA (Observational)

Detailed Description

RECONCILE is a single centre, prospective, longitudinal observational cohort study. 60 consenting men with intermediate risk, gleason 3+4, prostate cancer under active surveillance will be recruited to the study. They will undergo blinded, concurrent molecular and radiological analysis of their cancer at baseline and at one year. Tests at baseline and one year will include mpMRI, targeted prostate biopsy and further tissue sampling (semen, urine and blood). There will be PSA monitoring at 3 monthly intervals throughout the study as per standard of care active surveillance. Tissue will be analysed for biological and molecular markers significantly associated with radiological progression events.

After consenting to taking part in the study a patient will come in for an MRI scan as standard of care. This scan will be used at a subsequent visit to inform a guided trans-perineal biopsy. At this biopsy visit patients will provide research blood samples, a urine sample and have a confirmatory biopsy. After the standard of care diagnostic tissue samples are taken, three research tissue samples will be taken.

If the patient has been identified through the ReIMAGINE study and consents to take part in RECONCILE then these baseline visits are not needed, the data from ReIMAGINE will be used as the baseline visit data.

The patient will come in as scheduled for their regular PSA visits in line with their active surveillance protocol. If a PSA test shows signs of potential progression the patient will have a standard of care diagnostic MRI, if this confirms progression then the imaging and biopsy visits scheduled for one year will be triggered early.

In the absence of any identified progression the patient will return after 12 months and have both the imaging and biopsy visits repeated (again providing blood and urine). After this visit the patient will be considered as having finished the study.

Patients who consent to take part in the study who have previously taken part in the PLiS semen donation study will be asked to provide a semen sample before the one year biopsy visit for comparison with the baseline sample that was provided for the PLiS study.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • University College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Men over the age of 18 with prostate cancer (Gleason 3+4) who are on active surveillance.

Description

Inclusion Criteria:

• Male aged 18 years or above.
• Diagnosed with prostate cancer within 4 months of entry.
• Likert or PIRADS score greater than or equal to 4.
• PSA less than or equal to 15 ng.ml-1 in the last 6 months.
• mpMRI concordant with histology.
• Overall Gleason score 7 (3+4).
• Maximum cancer core length less than or equal to 10mm.
• Patients on active surveillance

Exclusion Criteria:

• Any contraindication to MRI scans (e.g. metal implants, unmanageable claustrophobia)
• Presence of a pacemaker
• Presence of a hip replacement
• Any hormonal treatment or inhibitors of 5 alpha-reductase in the previous 6 months
• Any previous TURP or other prostate surgery.
• Previous treatment for prostate cancer.
• Patients who have previously had sepsis due to a prostate biopsy
• Patients receiving concomitant treatment for their cancer
• Inability to provide full informed consent (e.g. due to dementia)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion	Proportion of concordant pairs molecular progressor- radiological progressor.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression time	Time to radiological progression	12 months
Lesion imaging characteristics	Quantitative and qualitative imaging characteristics of MRI lesions	12 months
Prostate imaging changes - quantitative	Quantitative imaging features (MRI and derivative) of MRI lesions(s), a radiological progression ring (if present) and the rest of the prostate at different time points	12 months
Prostate imaging changes - qualitative	Qualitative imaging features (MRI and derivative) of MRI lesion(s), a radiological progression ring (if present) and the rest of the prostate at different time points.	12 months
Imaging characteristics comparison	Quantitative imaging characteristics of MRI lesion(s), a radiological progression ring (if present) and the rest of the prostate at different time points and stratify by radiological progressors vs non progressors.	12 months
Histology	Qualitative and quantitative histologic composition of cancer and surrounding tissues	12 months
Heterogeneity	Histologic heterogeneity of cancer, both qualitatively and quantitatively	12 months
Molecular index	Molecular Index of cancer, peritumoral and normal tissue.	12 months
Urine and semen biomarkers	Next generation sequencing will be used to perform urinary and seminal genome, exosome, methylome and transcriptome analysis in order to identify novel molecular signatures associated with prostate cancer imaging endotypes. No commercial biomarkers will be assessed within this study. Biomarker definition (NIH NCI dictionary) A biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. Also called molecular marker and signature molecule.	12 months
Inflammatory infiltrate	Qualitative and quantitative analysis of inflammatory infiltrate in cancer, peritumoral and normal tissue.	12 months
Blood biomarkers	Deep sequencing of circulating plasma DNA will be be used to explore novel prostate cancer biomarkers. Analysis of circulating inflammatory and immune markers including T-cell analysis will be used to correlate immunological biomarkers with prostate cancer endotypes.	12 months
Immune pathways	Qualitative and quantitative analysis of immune related pathways	12 months
Transition to active treatment	Proportion of patients who transition to active treatment, by time and type of treatment.	12 months
Treatment eligibility	Proportion of patients eligible to a type of treatment at baseline and follow-up.	12 months
Rate of metastasis	Rate of metastasis for prostate cancer at different time point.	12 months
Concordance, histology and imaging	Concordance rate between progression at histology and imaging.	12 months
Concordance, radiology	Concordance rate between radiologist for PRECISE scoring.	12 months
Patient reported outcomes - EPIC 26	Patient reported outcomes at different time points using the RPIC 26 questionnaire	12 months
Patient reported outcomes - EORTC-QLQ-C30	Patient reported outcomes at different time points using the EORTC-QLQ-C30 questionnaire	12 months
Patient reported outcomes - MAX-PC	Patient reported outcomes at different time points using the MAX-PC questionnaire	12 months

Collaborators and Investigators

• Sponsor: University College, London

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Estimated): March 30, 2024
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: January 21, 2020
• First Submitted That Met QC Criteria: April 7, 2020
• First Posted (Actual): April 9, 2020

Study Record Updates

• Last Update Posted (Estimated): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: MRI; Prostate Cancer; MRI progression
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 127742

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No individual participant data will be shared. Patients will be identified by a pseudo-anonymised patient number

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No