Investigation of Three Biomarkers for the Detection of Prostate Cancer

Evaluation of the Performance of the Glycoscore Biomarkers for the Detection of Clinically Significant Prostate Cancer

GlycoScore Dx Limited, a diagnostics company based in the United Kingdom have identified three glycoproteins, that showed promise as biomarkers of prostate cancer in initial validation studies. The purpose of this study is to further evaluate the sensitivity and specificity of the GlycoScore biomarkers for the detection of clinically significant prostate cancer. Sensitivity and specificity will be determined for each marker, combinations of the three markers and combinations of the GlycoScore biomarkers with PSA (prostate specific antigen). The results from this study will be used to identify the most suitable biomarker/biomarkers for use in developing a GlycoScore test.

This is a prospective, non-interventional study using venous blood samples taken from patients with suspected prostate cancer or on active surveillance, attending the hospital Urology department for a transperineal biopsy.

Study Overview

• Status: Recruiting
• Conditions: Cancer of Prostate
• Intervention / Treatment: Diagnostic test: Laboratory Biomarker Analysis: Enzyme-linked immunosorbent assay (ELISA)

Detailed Description

Worldwide, prostate cancer is the most commonly diagnosed cancer in men and the fifth leading cause of cancer death in men. This amounted to 1,414,249 newly diagnosed cases and 375,000 deaths worldwide yearly from this disease in 2020. Globally, prostate cancer is the most commonly diagnosed cancer in more than fifty percent of countries (112 of 185). It presents a significant clinical burden in terms of volume and as a diagnostic challenge.

The initial diagnosis of prostate cancer relies on the detection of PSA (prostate specific antigen) in patient blood. While PSA is relatively good at identifying prostate cancer, PSA levels can be elevated for reasons other than cancer (giving a false positive result). Two thirds of men with a raised PSA level don't have prostate cancer meaning that many men undergo unnecessary & invasive follow up procedures, such as tissue biopsy. Prostate biopsies place a huge burden on both healthcare systems, and individuals with suspected prostate cancer. They are painful, can lead to complications, infections and in extreme circumstances, death.

Therefore, the poor specificity of the PSA test, combined with the disparate natural histories of many prostate cancers has limited its utility as a screening tool.

A combination of clinical and pathological features, such as the tumour grade (Gleason score or Gleason Grade Group), combined with clinical examination (digital rectal examination), MRI (magnetic resonance imaging) and isotope bone scan are commonly used to determine the aggressiveness and curability of tumours with radical treatment. PSA measurement is used as part of this assessment but, as other factors can influence PSA levels, it cannot be used to assess risk or guide treatment in isolation.

There remains an unmet clinical need for a better screening and diagnostic test for prostate cancer. Such a test must also be able to differentiate between early, low-risk cancers that do not require radical treatment and more aggressive tumours where radical treatment is preferable. By identifying which patients have a clinically significant risk of prostate cancer we believe our test could provide a solution to both.

The GlycoScore immunoassays detect the three biomarkers - 'glycosyltransferase enzymes' in patient blood (GALNT7, ST6GAL1 and GCNT1) which are linked to key tumour-associated glycans (types of sugars on cell walls) using an ELISA (enzyme-linked immunosorbent assay-based platform).

Initial studies conducted by Newcastle University using RUO (research use only) ELISA kits showed a significant correlation between prostate cancer and the three biomarkers ST6GAL1, GCNT1 and GALNT7. Extensive research and development work has been carried out developing custom antibody pairs and antigens for inclusion in our ELISA kit, as well as to optimize buffers and other components.

The purpose of this study is to obtain fresh patient blood samples to further evaluate the three biomarkers ST6GAL1, GCNT1 and GALNT7 for their ability to identify clinically significant prostate cancer, either alone, as a combination of the biomarkers or in combination with the PSA (measurement obtained at Medtechtomarket) using our in-house developed ELISA assays and a CE-marked PSA ELISA test kit.

Diagnostic accuracy for participants with prostate cancer will be determined by comparison with biopsy results, and for participants without prostate cancer, comparison with mpMRI (multi-parametric magnetic resonance imaging) and biopsy results.

Assessment of the correlation between the GlycoScore biomarker results with the full range of biopsy Gleason scores/Gleason Grade group/CPG grade (Cambridge Prognostic Group) will allow an assessment of the prognostic value of the GlycoScore test and its potential use in the clinical management of prostate cancer.

Patients attending the hospital for a transperineal prostate biopsy who are either being investigated for suspected prostate cancer or are undergoing active surveillance for previously diagnosed prostate cancer will be asked to consent to take part in the study. Patients will be asked to consent to have a small sample of blood taken before the biopsy and for study investigators to have access to their final diagnosis. The blood sample will be sent to Medtechtomarket Laboratories for measurement of the biomarkers and PSA. Patients will also be asked to consent to an additional tube of blood to be taken (from the same blood draw) and the urine sample, which is routinely taken before the biopsy to be sent to the Liverpool University Biobank for future use in research studies.

137 male patients aged 18 years and above will be recruited for the study which is expected to take 12 months.

• Study Type: Observational
• Enrollment (Estimated): 137

Contacts and Locations

• Study Contact: Name: Rebecca Newman, BSc; Phone Number: 07595 298 248; Email: rebecca.newman@medtechtomarket.com
• Study Contact Backup: Name: Lindsay Traynor, BSc; Email: lindsay.traynor@medtechtomarket.com

Study Locations

• United Kingdom
  • Liverpool, United Kingdom, L7 8XP
    • Recruiting
    • Royal Liverpool University Hospital
    • Contact: Henry P Lazarowicz, BMBS BMedSci PhD FRCS(Urol); Email: henry.lazarowicz@liverpoolft.nhs.uk
    • Contact: Email: henry.lazarowicz@liverpoolft.nhs.uk
    • Principal Investigator: Henry P Lazarowicz, BMBS BMedSci PhD FRCS(Urol)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Male patients referred to the secondary care (urology clinic) for transperineal biopsy for the investigation of suspected prostate cancer or patients undergoing active surveillance

Description

Inclusion Criteria:

• Male patients aged 18 years and over
• The patient is being investigated for suspected prostate cancer or is on active surveillance
• The patient is able to give consent to take part in the study

Exclusion Criteria:

• A patient who has already taken part in the study
• A patient with an active urinary tract infection
• The patient has a prior diagnosis of any other cancer or is receiving any cancer treatment (including ADT)
• The patient is currently or within the last 4 months enrolled on another study involving an investigational medicinal product

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with suspected prostate cancer or on active surveillance; Diagnostic tests to measure three separate biomarkers in blood taken from patients pre-biopsy to assess the diagnostic performance of the biomarkers in detecting clinically significant prostate cancer (Gleason score ≥7)	Diagnostic test: Laboratory Biomarker Analysis: Enzyme-linked immunosorbent assay (ELISA); Measurement of the plasma concentration of ST6GAL1, GCNT1 and GALNT7 biomarkers in patients suspected of having prostate cancer or on active surveillance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
An evaluation of the diagnostic performance of the GlycoScore biomarkers for the detection of clinically significant prostate cancer (Gleason score of ≥7).	A comparison of calculated sensitivity, specificity and positive and negative predictive values for clinically significant prostate cancer for the following: Each biomarker, alone and in combination with PSA (measured on from the same blood sample using a CE-marked assay) Each possible combination of GlycoScore biomarkers, alone and in combination with PSA The reference method for diagnosis of prostate cancer will be biopsy, and the reference method for identifying patients who do not have cancer will be by a combination of mpMRI and/or biopsy.	Pre-biopsy (one time point)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Establishment of a 'GlycoScore' algorithm	Establish an algorithm for calculating a 'GlycoScore' that converts the assay results from the optimal combination of biomarkers into a score that indicates the likelihood that a patient has clinically significant prostate cancer (Gleason score of ≥7).	Pre-biopsy (one time point)
An evaluation of the ability of the calculated 'GlycoScore' to distinguish between individual Gleason scores and grade groups	Correlation between the calculated 'GlycoScore' from each sample and Gleason score and grade groups at biopsy	Pre-biopsy (one time point)
An evaluation of the ability of the calculated 'GlycoScore' to distinguish between CPG groups 1 to 5 (Cambridge Prognostic Group classification)	Correlation between the calculated 'GlycoScore' from each sample and the Cambridge Prognostic Group classification	Pre-biopsy (one time point)
A comparison of the diagnostic performance of the GlycoScore biomarkers (with and without PSA) against the performance of the hospital PSA test alone for the detection of clinically significant prostate cancer (Gleason score of ≥7).	A comparison of calculated sensitivity, specificity and positive and negative predictive values for clinically significant prostate cancer	Pre-biopsy (one time point)

Collaborators and Investigators

• Sponsor: Medtechtomarket Consulting Ltd
• Collaborators: GlycoscoreDx Ltd
• Investigators: Principal Investigator: Henry P Lazarowicz, FRCS(Urol), Liverpool University Hospitals NHS Foundation Trust

Publications and helpful links

General Publications

• Flahault A, Cadilhac M, Thomas G. Sample size calculation should be performed for design accuracy in diagnostic test studies. J Clin Epidemiol. 2005 Aug;58(8):859-62. doi: 10.1016/j.jclinepi.2004.12.009.
• Tuck MK, Chan DW, Chia D, Godwin AK, Grizzle WE, Krueger KE, Rom W, Sanda M, Sorbara L, Stass S, Wang W, Brenner DE. Standard operating procedures for serum and plasma collection: early detection research network consensus statement standard operating procedure integration working group. J Proteome Res. 2009 Jan;8(1):113-7. doi: 10.1021/pr800545q.
• Roddam AW, Duffy MJ, Hamdy FC, Ward AM, Patnick J, Price CP, Rimmer J, Sturgeon C, White P, Allen NE; NHS Prostate Cancer Risk Management Programme. Use of prostate-specific antigen (PSA) isoforms for the detection of prostate cancer in men with a PSA level of 2-10 ng/ml: systematic review and meta-analysis. Eur Urol. 2005 Sep;48(3):386-99; discussion 398-9. doi: 10.1016/j.eururo.2005.04.015.
• Catalona WJ, Hudson MA, Scardino PT, Richie JP, Ahmann FR, Flanigan RC, DeKernion JB, Ratliff TL, Kavoussi LR, Dalkin BL, Waters WB, MacFarlane MT, Southwick PC. Selection of optimal prostate specific antigen cutoffs for early detection of prostate cancer: receiver operating characteristic curves. J Urol. 1994 Dec;152(6 Pt 1):2037-42. doi: 10.1016/s0022-5347(17)32300-5.
• Johnston E, Pye H, Bonet-Carne E, Panagiotaki E, Patel D, Galazi M, Heavey S, Carmona L, Freeman A, Trevisan G, Allen C, Kirkham A, Burling K, Stevens N, Hawkes D, Emberton M, Moore C, Ahmed HU, Atkinson D, Rodriguez-Justo M, Ng T, Alexander D, Whitaker H, Punwani S. INNOVATE: A prospective cohort study combining serum and urinary biomarkers with novel diffusion-weighted magnetic resonance imaging for the prediction and characterization of prostate cancer. BMC Cancer. 2016 Oct 21;16(1):816. doi: 10.1186/s12885-016-2856-2.

Helpful Links

• Prostate cancer: diagnosis and management - current UK NICE guidelines
• Current NICE guidelines - Evidence review covering the definition of clinically significant prostate cancer, page 17

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2025
• Primary Completion (Estimated): January 7, 2026
• Study Completion (Estimated): March 7, 2026

Study Registration Dates

• First Submitted: August 12, 2024
• First Submitted That Met QC Criteria: August 12, 2024
• First Posted (Actual): August 15, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 16, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: M2M-GLYCOSCORE-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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