Early Diagnosis of Colorectal Cancer Based on a Non-invasive Metabolomics Profile (EarlyCRC)

Colorectal cancer is the most frequent tumor in our environment if both sexes are considered together. Every year almost 800 cases are diagnosed in the districts of Tarragona. A little more than half of colorectal cancers are cured with surgery, with or without the addition of complementary treatments with chemotherapy and/or radiation therapy. Those who are not cured is because at the time of diagnosis the disease has already spread or they spread after having been treated surgically with curative intent.

The purpose of the EarlyCRC project is to determine whether metabolites (substances of low molecular weight) can be found in the urine and stool of patients with colorectal cancer or polyps that can be easily and cheaply differentiated (urine or stool analysis) between the patients affected by colorectal cancer or polyps, from healthy individuals. For the identification of these possible metabolites, the urine analysis will be performed using the usual techniques in metabolomics, which studies the existing metabolites in biological processes.

Study Overview

• Status: Recruiting
• Conditions: Healthy; Colorectal Cancer; Colorectal Adenoma; Colorectal Polyp
• Intervention / Treatment: Procedure: Colonoscopy; Other: Urine and FOBT collection

Detailed Description

Colorectal cancer (CRC) is the most frequent neoplasm in our environment if both sexes are considered together. It is the second most common neoplasm in women, after breast cancer, and the second most common in men after prostate cancer. In terms of mortality, CRC is the second leading cause of cancer death in men, after lung cancer, and second in women after breast cancer. For the year 2013, 735 cases and 262 deaths from colorectal cancer were estimated in the province of Tarragona. Since 1982, incidence rates have increased annually by more than 3% in men and by almost 2% in women. It is estimated that if no early diagnosis program was carried out, in 2020 about 900 new cases of CRC would be diagnosed, and about 300 deaths would occur1.

These figures vary according to one or other geographical areas of the world. If we consider the European population as a whole, colorectal cancer is the third most common tumor for both sexes together, after breast cancer and prostate cancer. It is the third most common tumor in men, after prostate cancer and lung cancer, and the second most common in women, after breast cancer. The mortality figures in Europe place colorectal cancer in third place for both sexes together, after lung and breast cancer, so that in men it is surpassed only by lung cancer and in women by breast cancer2 .

As in the vast majority of cancers, age is the main non-modifiable risk factor for colon and rectal cancer. More than 90% of cases are diagnosed in people over 50 years old. There is an increased risk of CRC in those with hereditary diseases such as familial colonic polyposis or Lynch syndrome, although the vast majority of colorectal cancers (more than 90% of cases) do not have a hereditary component. With respect to the modifiable risk factors, one of the most important is the consumption of red and processed meat, or meat that is heavily cooked or cooked in direct contact with fire. On the other hand, fiber, fruit and vegetable consumption, as well as dairy and micronutrients such as folate and calcium, are protective against this cancer. All these dietary factors affect the risk of the appearance of the precursor lesions of cancer, colorectal adenomas. Obesity is another risk factor, and exercise and physical activity act as protectors. Thus, CRC is considered to be caused by a combination of genetic and environmental factors, which lead to the appearance of adenomatous polyps as a premalignant lesion, and which over time acquire new mutations in their genetic material until become an adenocarcinoma1,3.

The early diagnosis of cancer and, more specifically, that of colorectal cancer, aims to detect colorectal tumors in the initial stages as well as premalignant lesions, colonic polyps. As with all neoplastic diseases, the stage at the time of diagnosis is the most important prognostic factor when it comes to survival. In this way, it has been shown that a test capable of easily and minimally invasively diagnosing the initial stages of colorectal cancer can reduce mortality from this tumor by 15-20% in program participants4. The fact of being able to detect benign polyps not only reduces mortality from colorectal cancer, but also decreases its incidence, since the removal of polyps prevents their subsequent malignancy. Currently, the test used in the early diagnosis of colorectal cancer is the determination of occult blood in faeces from the age of 50, every two years. In the event that the test comes out positive, the patient is subsequently subjected to a colonoscopic study. Collection of the faecal sample by itself may have low acceptance and therefore may compromise population participation in screening. A urine test, with an easier and "cleaner" collection technique, could be an added advantage in an early diagnosis program.

• Study Type: Observational
• Enrollment (Estimated): 2000

Contacts and Locations

Study Locations

• Spain
  • Tarragona, Spain, 43005
    • Recruiting
    • Hospital Universitari Joan XXIII
    • Contact: Joan C Quer-Boniquet, PhD; Phone Number: +34977295800; Email: jquer.hj23.ics@gencat.cat
    • Contact: Joan C Quer-Boniquet, MD
    • Contact: Belén Ballesté-Peris, MD
    • Contact: Lidia Cabrinety-Fernández, MD
    • Contact: Maria L Díaz-Fernández, MD
    • Contact: Miriam Gené-Hijós, MD
  • Tarragona
    • Reus, Tarragona, Spain, 43204
      • Recruiting
      • Hospital Universitari Sant Joan de Reus
      • Contact: Josep Gumà, PhD; Phone Number: +34977310300; Email: josep.guma@salutsantjoan.cat
      • Contact: Josep Gumà, PhD
      • Contact: Raquel Cumeras, PhD
      • Contact: Cristina Miracle, MSc
      • Contact: Maria Llambrich, MSc
      • Contact: Jaume Galceran, PhD
      • Contact: Teresa Sans, PhD
      • Contact: Francesc Martínez-Cerezo
      • Contact: Francesc Riu

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

The cohort subject to the study are patients participating in the population screening program for colorectal cancer with a positive fecal occult blood test (FOBT) who are called to undergo a colonoscopy.

Description

Inclusion Criteria:

• Patients with a positive FOBT test result from the Colorectal Cancer Early Detection Program and referred for a colonoscopy.

Exclusion Criteria:

• Patients diagnosed with another primary neoplasm in the last 5 years, with the exception of carcinoma in situ of the cervix or non-melanoma skin cancer.
• Patients with severe kidney disease stage IV (creatinine clearance < 30 ml/min).
• Patients with severe active liver disease (hepatitis, cirrhosis).
• Refusal to sign informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Colorectal Cancer; Diagnosed colorectal cancer after histopathological analysis of biopsy and polypectomy pieces taken within a colonoscopy.	Procedure: Colonoscopy; Colonoscopy performed as a regular practice during colorectal cancer screening.; Other: Urine and FOBT collection; After patients agreement, urine and FOBT are collected before the colonoscopy and before the diet preparation of the colon.
Adenomatous high risk polyps; Diagnosed adenomatous high risk polyps after histopathological analysis of biopsy and polypectomy pieces taken within a colonoscopy. With = or > 10 adenomas or serrated polyps and/or any sessile or flat lesion of = or >20 mm (pediculated = or >20 mm are not high risk).	Procedure: Colonoscopy; Colonoscopy performed as a regular practice during colorectal cancer screening.; Other: Urine and FOBT collection; After patients agreement, urine and FOBT are collected before the colonoscopy and before the diet preparation of the colon.
Adenomatous medium risk polyps; Diagnosed adenomatous medium risk polyps after histopathological analysis of biopsy and polypectomy pieces taken within a colonoscopy. With 5 to 9 non-advanced serrated adenomas or polyps and/or at least 1 advanced lesion (adenoma >10mm and/or hairy component and/or high-grade dysplasia or serrated polyp >10mm and/or dysplasia).	Procedure: Colonoscopy; Colonoscopy performed as a regular practice during colorectal cancer screening.; Other: Urine and FOBT collection; After patients agreement, urine and FOBT are collected before the colonoscopy and before the diet preparation of the colon.
Adenomatous low risk polyps; Diagnosed adenomatous low risk polyps after histopathological analysis of biopsy and polypectomy pieces taken within a colonoscopy. With 1 to 4 non-advanced adenomas (<10mm, without hairy component or high-grade dysplasia) or non-advanced serrated polyps (<10mm, without dysplasia).	Procedure: Colonoscopy; Colonoscopy performed as a regular practice during colorectal cancer screening.; Other: Urine and FOBT collection; After patients agreement, urine and FOBT are collected before the colonoscopy and before the diet preparation of the colon.
Healthy; No luminal lesions are observed during the colonoscopy.	Procedure: Colonoscopy; Colonoscopy performed as a regular practice during colorectal cancer screening.; Other: Urine and FOBT collection; After patients agreement, urine and FOBT are collected before the colonoscopy and before the diet preparation of the colon.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Colonoscopy results	Histopathological analysis of biopsy and polypectomy pieces.	3 months

Collaborators and Investigators

• Sponsor: Institut Investigacio Sanitaria Pere Virgili

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2019
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): June 30, 2040

Study Registration Dates

• First Submitted: June 5, 2024
• First Submitted That Met QC Criteria: June 5, 2024
• First Posted (Actual): June 11, 2024

Study Record Updates

• Last Update Posted (Actual): October 2, 2024
• Last Update Submitted That Met QC Criteria: September 30, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: biomarkers; urine; screening; metabolomics; fobt
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Adenoma
• Other Study ID Numbers: 114/2019

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
• product manufactured in and exported from the U.S.: No