SCARLET - Italian proSpeCtionAl obseRvationaL multicEntre Study on Treatment for recTal pT1 Cancer (SCARLET)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Rectal Cancer; Rectal Adenocarcinoma; Rectal Cancer Patients; Rectal Cancer, Radiotherapy

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 Type: Observational
• Enrollment (Estimated): 196

Contacts and Locations

• Study Contact: Name: Giuditta Chiloiro, MD, Phd; Phone Number: 06-30154981; Email: giuditta.chiloiro@policlinicogemelli.it

Study Locations

• Italy
  • RM
    • Roma, RM, Italy, 00168
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
      • Contact: Giuditta Chiloiro, MD, Phd; Phone Number: 06-30154981; Email: giuditta.chiloiro@policlinicogemelli.it

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

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.

Description

Inclusion Criteria:

1. Age 18 years or older.
2. Good performance status (Eastern Cooperative Oncology Group [ECOG] performance status 0 or 1).
3. 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).

4. High-risk pathological T1 rectal cancer meeting at least one of the following conditions:

   i) Poorly differentiated adenocarcinoma, mucinous adenocarcinoma, or signet ring cell carcinoma.

   ii) Pathological submucosal invasion greater than 1000 micrometers. iii) Positive lymphatic invasion or positive venous invasion confirmed by immunohistochemistry.

   iv) 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.

5. No lymph node or distant metastases confirmed by computed tomography of the chest, abdomen, and pelvis (clinical N0, M0 disease).
6. Radiotherapy or chemoradiotherapy initiated within 12 weeks after local endoscopic or surgical resection.
7. No previous rectal resection (other than local excision) or pelvic irradiation for any malignancy.
8. Adequate organ function as assessed by the treating physician.
9. 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.
10. Candidate for adjuvant chemoradiotherapy according to routine clinical practice.
11. Written informed consent provided.

Exclusion Criteria:

1. Synchronous or metachronous malignancy diagnosed within the previous 5 years.
2. Infection requiring systemic treatment.
3. Requirement for continuous systemic treatment with corticosteroids or immunosuppressive agents.
4. 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.
5. Squamous cell carcinoma, neuroendocrine neoplasm, or mixed neuroendocrine-non-neuroendocrine neoplasm histology.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	3-years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	5 years
Overall survival at 1 year	Percentage of patients alive at 1 year from the start of follow-up.	1 year
Overall survival at 3 years	Percentage of patients alive at 3 years from the start of follow-up.	3 years
Overall survival at 5 years	Percentage of patients alive at 5 years from the start of follow-up.	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.	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.	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.	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.	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.	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.	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.	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.	2 years after the end of treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nodal Recurrence Rate	ercentage of patients who develop regional lymph node recurrence during the follow-up period, as assessed by imaging modalities.	Up to 5 years after completion of adjuvant treatment.
Distant Metastases Rate	Percentage of patients who develop distant organ metastases (outside the pelvis) during the follow-up period, confirmed by contrast-enhanced chest-abdomen-pelvis CT scan.	Up to 5 years after completion of adjuvant treatment.

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: Giuditta Chiloiro, MD, PhD, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2031

Study Registration Dates

• First Submitted: July 1, 2026
• First Submitted That Met QC Criteria: July 8, 2026
• First Posted (Actual): July 10, 2026

Study Record Updates

• Last Update Posted (Actual): July 10, 2026
• Last Update Submitted That Met QC Criteria: July 8, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: ESD; TAMIS; Endoscopic Submucosal Dissection; Adjuvant Radiotherapy; Transanal Endoscopic Microsurgery; TEM; Transanal Minimally Invasive Surgery; Organ Preservation; Adjuvant Chemoradiotherapy; High-Risk Factors; Local Excision; pT1 Rectal Cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms
• Other Study ID Numbers: 27321

Drug and device information, study documents

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