Rectal CancerSCARLETNCT07695519
SCARLET - Italian proSpeCtionAl obseRvationaL multicEntre Study on Treatment for recTal pT1 Cancer
An observational study of Rectal Cancer and Rectal Adenocarcinoma, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
Trial summary
The purpose of this prospective, observational, multicenter study is to evaluate the impact of adjuvant radiotherapy or chemoradiotherapy on disease-free survival (DFS) in patients with pathological T1 (pT1) rectal cancer presenting with at least one high-risk histological factor, such as deep submucosal invasion… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Cancer, Rectal Adenocarcinoma, Rectal Cancer Patients
- How many people
- 196 participants
- Where
- 1 siteItaly
- Study dates
- Sep 2026to Sep 2031
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: dult patients with high-risk pathological T1 (pT1) rectal cancer who have undergone local endoscopic resection using Endoscopic Submucosal Dissection (ESD) or local surgical resection using Transanal Endoscopic Microsurgery (TEM) or Transanal Minimally Invasive Surgery (TAMIS). The study population specifically includes patients who have declined standard treatment with Total Mesorectal Excision (TME) and who subsequently receive adjuvant radiotherapy or chemoradiotherapy according to routine clinical practice following multidisciplinary team evaluation.
Who may be able to join
- Age 18 years or older.
- Good performance status (Eastern Cooperative Oncology Group [ECOG] performance status 0 or 1).
- Primary tumor of the distal rectum (clinical T1) amenable to local endoscopic resection using Endoscopic Submucosal Dissection (ESD) or local surgical resection using Transanal Endoscopic Microsurgery (TEM) or Transanal Minimally Invasive Surgery (TAMIS).
- High-risk pathological T1 rectal cancer meeting at least one of the following conditions:
- Poorly differentiated adenocarcinoma, mucinous adenocarcinoma, or signet ring cell carcinoma.
- Pathological submucosal invasion greater than 1000 micrometers. iii) Positive lymphatic invasion or positive venous invasion confirmed by immunohistochemistry.
Show all 14Show fewer
- Tumor budding grade 2 or 3. v) Positive lateral or vertical resection margin (tumor within 1 mm of the surgical margin) or non-assessable resection margin.
- No lymph node or distant metastases confirmed by computed tomography of the chest, abdomen, and pelvis (clinical N0, M0 disease).
- Radiotherapy or chemoradiotherapy initiated within 12 weeks after local endoscopic or surgical resection.
- No previous rectal resection (other than local excision) or pelvic irradiation for any malignancy.
- Adequate organ function as assessed by the treating physician.
- The treating surgeons have explained to the patient that the current standard of care is Total Mesorectal Excision (TME) with D2 lymph node dissection and the patient has declined this treatment.
- Candidate for adjuvant chemoradiotherapy according to routine clinical practice.
- Written informed consent provided.
Who cannot join
- Synchronous or metachronous malignancy diagnosed within the previous 5 years.
- Infection requiring systemic treatment.
- Requirement for continuous systemic treatment with corticosteroids or immunosuppressive agents.
- Diagnosis of a hereditary colorectal cancer syndrome, including familial adenomatous polyposis or Lynch syndrome, or diagnosis of inflammatory bowel disease, including ulcerative colitis or Crohn disease.
- Squamous cell carcinoma, neuroendocrine neoplasm, or mixed neuroendocrine-non-neuroendocrine neoplasm histology.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Roma, RM, 00168
Giuditta Chiloiro, MD, Phd, 06-30154981, giuditta.chiloiro@policlinicogemelli.it
About this study
The purpose of this prospective, observational, multicenter study is to evaluate the impact of adjuvant radiotherapy or chemoradiotherapy on disease-free survival (DFS) in patients with pathological T1 (pT1) rectal cancer presenting with at least one high-risk histological factor, such as deep submucosal invasion, poor differentiation, tumor budding, lymphovascular invasion, or positive resection margins, after local surgical or endoscopic excision, including Endoscopic Submucosal Dissection (ESD), Transanal Minimally Invasive Surgery (TAMIS), or Transanal Endoscopic Microsurgery (TEM). The study focuses on a specific patient population that has refused standard radical surgery with Total Mesorectal Excision (TME) because of its potential impact on quality of life and postoperative morbidity. The primary objective is to assess whether organ-preserving local treatment strategies can provide an effective alternative by evaluating long-term oncologic outcomes, quality of life, and colostomy-free survival.
Read the detailed description
Background To date, the therapeutic management of patients with pathological T1 (pT1) rectal cancer after local surgical or endoscopic excision remains a subject of ongoing debate. Although traditional radical surgery has demonstrated proven advantages, discussion persists regarding the adequacy of less invasive techniques for specific subgroups of patients, particularly those with a low risk of disease progression. In these cases, local excision options through endoscopic or surgical interventions, including Endoscopic Submucosal Dissection (ESD), Transanal Minimally Invasive Surgery (TAMIS), and Transanal Endoscopic Microsurgery (TEM), may represent a valid curative approach. These techniques, which generally carry a low risk of lymph node metastasis, offer important advantages in terms of organ preservation and reduction of postoperative complications, including anorectal, urinary, and sexual dysfunction, which may significantly impair quality of life.
Rationale The choice of a conservative approach must be carefully evaluated, especially when post-excision histopathological analysis reveals high-risk features. These include deep submucosal invasion greater than 1 mm, poor tumor differentiation, tumor budding, lymphovascular invasion, or positive or close resection margins. In these situations, radical surgery with Total Mesorectal Excision (TME) is considered the standard treatment strategy for reducing the risk of local and nodal recurrence, although available evidence is largely derived from retrospective studies. Because TME may substantially affect quality of life and functional outcomes, treatment decisions should be discussed within a multidisciplinary team. National and international guidelines suggest that patients with pT1 rectal cancer who present high-risk features and are either unwilling or unsuitable to undergo radical surgery may be considered for alternative organ-preserving strategies, including adjuvant radiotherapy or chemoradiotherapy.
Study Objective This prospective, observational, multicenter study aims to evaluate the impact of adjuvant radiotherapy or chemoradiotherapy on Disease-Free Survival (DFS) in patients with pT1 rectal cancer presenting at least one high-risk histopathological feature who have undergone local excision and declined treatment with TME. The study will also assess long-term oncologic outcomes, organ preservation, and quality of life in this patient population.
- Keywords
- pT1 Rectal Cancer, Local Excision, Transanal Minimally Invasive Surgery, TAMIS, Transanal Endoscopic Microsurgery, TEM, Endoscopic Submucosal Dissection, ESD, Adjuvant Radiotherapy, Adjuvant Chemoradiotherapy, High-Risk Factors, Organ Preservation
- Medical subject headings
- Rectal Neoplasms
What is being measured
The primary outcome is the main question the study is designed to answer.
3-year Disease-Free Survival (DFS)
Percentage of patients who remain alive and free from rectal cancer recurrence (local, nodal, or distant metastases) at three years from the start of follow-up.
Measured: 3-years
Secondary outcomes (16)
Disease-free survival at 1 year
Percentage of patients alive and free from rectal cancer recurrence (local, nodal, or distant metastases) at 1 year from follow-up.
Measured: 1 year
Disease-free survival at 5 years
Percentage of patients alive and free from rectal cancer recurrence (local, nodal, or distant metastases) at 5 years from follow-up.
Measured: 5 years
Local recurrence-free survival at 1 year
Time from the end of treatment to the documentation of local disease recurrence at 1 year.
Measured: 1 year
Local recurrence-free survival at 3 years
Time from the end of treatment to the documentation of local disease recurrence at 3 years.
Measured: 3 years
Local recurrence-free survival at 5 years
Time from the end of treatment to the documentation of local disease recurrence at 5 years.
Measured: 5 years
Overall survival at 1 year
Percentage of patients alive at 1 year from the start of follow-up.
Measured: 1 year
Overall survival at 3 years
Percentage of patients alive at 3 years from the start of follow-up.
Measured: 3 years
Overall survival at 5 years
Percentage of patients alive at 5 years from the start of follow-up.
Measured: 5 years
Colostomy-free survival at 1 year
Percentage of patients alive without the need for a temporary or permanent stoma/colostomy at 1 year.
Measured: 1 year
Colostomy-free survival at 3 years
Percentage of patients alive without the need for a temporary or permanent stoma/colostomy at 3 years.
Measured: 3 years
Quality of life assessed by EORTC QLQ-C30 Global Health Status/Quality of Life score at 1 year
Patient-reported quality of life assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). The Global Health Status/Quality of Life score ranges from 0 to 100 after linear transformation. Higher scores indicate better quality of life.
Measured: 1 year
Colorectal cancer-specific quality of life assessed by EORTC QLQ-CR29 at 1 year
Patient-reported colorectal cancer-specific quality of life assessed using the European Organisation for Research and Treatment of Cancer Colorectal Cancer Questionnaire (EORTC QLQ-CR29). Questionnaire scores are transformed to a 0-100 scale. For functional scales, higher scores indicate better functioning; for symptom scales, higher scores indicate greater symptom burden. Individual QLQ-CR29 scale scores will be analyzed separately.
Measured: 1 year
Quality of life assessed by EORTC QLQ-C30 Global Health Status/Quality of Life score at 3 years
Patient-reported quality of life assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). The Global Health Status/Quality of Life score ranges from 0 to 100 after linear transformation. Higher scores indicate better quality of life.
Measured: 3 years
Colorectal cancer-specific quality of life assessed by EORTC QLQ-CR29 at 3 years
Patient-reported colorectal cancer-specific quality of life assessed using the European Organisation for Research and Treatment of Cancer Colorectal Cancer Questionnaire (EORTC QLQ-CR29). Questionnaire scores are transformed to a 0-100 scale. For functional scales, higher scores indicate better functioning; for symptom scales, higher scores indicate greater symptom burden. Individual QLQ-CR29 scale scores will be analyzed separately.
Measured: 3 years
Acute toxicity within 6 months from treatment
Incidence and severity of acute adverse events (genitourinary, gastrointestinal, and hematologic) scored according to CTCAE version 5.0.
Measured: Within 6 months from the end of treatment
Late toxicity at 2 years after the end of treatment
Incidence and severity of long-term treatment-related toxicities scored according to CTCAE version 5.0.
Measured: 2 years after the end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2026
- Study startSep 2026 (estimated)
- Primary completionSep 2029 (estimated)
- Study completionSep 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rectal CancerStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 196 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, CHILOIRO GIUDITTA, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Investigators
- Giuditta Chiloiro, MD, PhD, Principal investigator, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07695519
- Sponsor's protocol ID
- 27321
- Acronym
- SCARLET
- Status last verified
- Jul 2026
- First submitted
- 1 Jul 2026
- Last updated
- 10 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SCARLET - Italian proSpeCtionAl obseRvationaL multicEntre Study on Treatment for recTal pT1 Cancer
- ClinicalTrials.gov ID
- NCT07695519
- Acronym / sponsor ID
- SCARLET / 27321
- Keywords
- pT1 Rectal Cancer, Local Excision, Transanal Minimally Invasive Surgery, TAMIS, Transanal Endoscopic Microsurgery, TEM, Endoscopic Submucosal Dissection, ESD
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 196 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Study start
- Sep 2026 (estimated)
- Primary completion
- Sep 2029 (estimated)
- Study completion
- Sep 2031 (estimated)
- First posted
- 10 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this prospective, observational, multicenter study is to evaluate the impact of adjuvant radiotherapy or chemoradiotherapy on disease-free survival (DFS) in patients with pathological T1 (pT1) rectal cancer presenting with at least one high-risk histological factor, such as deep submucosal invasion, poor differentiation, tumor budding, lymphovascular invasion, or positive resection margins, after local surgical or endoscopic excision, including Endoscopic Submucosal Dissection (ESD), Transanal Minimally Invasive Surgery (TAMIS), or Transanal Endoscopic Microsurgery (TEM). The study focuses on a specific patient population that has refused standard radical surgery with Total Mesorectal Excision (TME) because of its potential impact on quality of life and postoperative morbidity. The primary objective is to assess whether organ-preserving local treatment strategies can provide an effective alternative by evaluating long-term oncologic outcomes, quality of life, and colostomy-free survival.
Detailed description
Background To date, the therapeutic management of patients with pathological T1 (pT1) rectal cancer after local surgical or endoscopic excision remains a subject of ongoing debate. Although traditional radical surgery has demonstrated proven advantages, discussion persists regarding the adequacy of less invasive techniques for specific subgroups of patients, particularly those with a low risk of disease progression. In these cases, local excision options through endoscopic or surgical interventions, including Endoscopic Submucosal Dissection (ESD), Transanal Minimally Invasive Surgery (TAMIS), and Transanal Endoscopic Microsurgery (TEM), may represent a valid curative approach. These techniques, which generally carry a low risk of lymph node metastasis, offer important advantages in terms of organ preservation and reduction of postoperative complications, including anorectal, urinary, and sexual dysfunction, which may significantly impair quality of life.
Rationale The choice of a conservative approach must be carefully evaluated, especially when post-excision histopathological analysis reveals high-risk features. These include deep submucosal invasion greater than 1 mm, poor tumor differentiation, tumor budding, lymphovascular invasion, or positive or close resection margins. In these situations, radical surgery with Total Mesorectal Excision (TME) is considered the standard treatment strategy for reducing the risk of local and nodal recurrence, although available evidence is largely derived from retrospective studies. Because TME may substantially affect quality of life and functional outcomes, treatment decisions should be discussed within a multidisciplinary team. National and international guidelines suggest that patients with pT1 rectal cancer who present high-risk features and are either unwilling or unsuitable to undergo radical surgery may be considered for alternative organ-preserving strategies, including adjuvant radiotherapy or chemoradiotherapy.
Study Objective This prospective, observational, multicenter study aims to evaluate the impact of adjuvant radiotherapy or chemoradiotherapy on Disease-Free Survival (DFS) in patients with pT1 rectal cancer presenting at least one high-risk histopathological feature who have undergone local excision and declined treatment with TME. The study will also assess long-term oncologic outcomes, organ preservation, and quality of life in this patient population.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- dult patients with high-risk pathological T1 (pT1) rectal cancer who have undergone local endoscopic resection using Endoscopic Submucosal Dissection (ESD) or local surgical resection using Transanal Endoscopic Microsurgery (TEM) or Transanal Minimally Invasive Surgery (TAMIS). The study population specifically includes patients who have declined standard treatment with Total Mesorectal Excision (TME) and who subsequently receive adjuvant radiotherapy or chemoradiotherapy according to routine clinical practice following multidisciplinary team evaluation.
Key inclusion criteria (14 listed)
- Age 18 years or older.
- Good performance status (Eastern Cooperative Oncology Group [ECOG] performance status 0 or 1).
- Primary tumor of the distal rectum (clinical T1) amenable to local endoscopic resection using Endoscopic Submucosal Dissection (ESD) or local surgical resection using Transanal Endoscopic Microsurgery (TEM) or Transanal Minimally Invasive Surgery (TAMIS).
- High-risk pathological T1 rectal cancer meeting at least one of the following conditions:
- No lymph node or distant metastases confirmed by computed tomography of the chest, abdomen, and pelvis (clinical N0, M0 disease).
Key exclusion criteria (5 listed)
- Synchronous or metachronous malignancy diagnosed within the previous 5 years.
- Infection requiring systemic treatment.
- Requirement for continuous systemic treatment with corticosteroids or immunosuppressive agents.
- Diagnosis of a hereditary colorectal cancer syndrome, including familial adenomatous polyposis or Lynch syndrome, or diagnosis of inflammatory bowel disease, including ulcerative colitis or Crohn disease.
- Squamous cell carcinoma, neuroendocrine neoplasm, or mixed neuroendocrine-non-neuroendocrine neoplasm histology.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
3-year Disease-Free Survival (DFS)
Time frame: 3-years
Percentage of patients who remain alive and free from rectal cancer recurrence (local, nodal, or distant metastases) at three years from the start of follow-up.
16 secondary outcomes
Disease-free survival at 1 year
Time frame: 1 year
Disease-free survival at 5 years
Time frame: 5 years
Local recurrence-free survival at 1 year
Time frame: 1 year
Local recurrence-free survival at 3 years
Time frame: 3 years
Local recurrence-free survival at 5 years
Time frame: 5 years
Overall survival at 1 year
Time frame: 1 year
Overall survival at 3 years
Time frame: 3 years
Overall survival at 5 years
Time frame: 5 years
Colostomy-free survival at 1 year
Time frame: 1 year
Colostomy-free survival at 3 years
Time frame: 3 years
Quality of life assessed by EORTC QLQ-C30 Global Health Status/Quality of Life score at 1 year
Time frame: 1 year
Colorectal cancer-specific quality of life assessed by EORTC QLQ-CR29 at 1 year
Time frame: 1 year
Quality of life assessed by EORTC QLQ-C30 Global Health Status/Quality of Life score at 3 years
Time frame: 3 years
Colorectal cancer-specific quality of life assessed by EORTC QLQ-CR29 at 3 years
Time frame: 3 years
Acute toxicity within 6 months from treatment
Time frame: Within 6 months from the end of treatment
Late toxicity at 2 years after the end of treatment
Time frame: 2 years after the end of treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Giuditta Chiloiro, MD, PhD principal investigator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Rectal Cancer and Rectal Adenocarcinoma, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 10 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Giuditta Chiloiro, MD, Phd (06-30154981, giuditta.chiloiro@policlinicogemelli.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
3-year Disease-Free Survival (DFS) (time frame: 3-years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2026.