Ignite Creation Date:
2024-05-06 @ 7:32 PM
Last Modification Date:
2025-12-16 @ 6:35 PM
Study NCT ID:
NCT06040632
Status:
None
Last Update Posted:
2025-04-01 00:00:00
First Post:
2023-08-31 00:00:00
Brief Title:
IMPROVE-pT1: Accurate Allocation of Completion Resection in Early Colorectal Cancer
Sponsor:
University of Aarhus
Organization:
University of Aarhus
Study Overview
Official Title:
Accurate Allocation of Completion Resection in Early Colorectal Cancer: an Observational Cohort Study
Status:
None
Status Verified Date:
2025-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
KEY POINTS
* 85% of patients receiving completion bowel resection after local removal of pT1 CRC are overtreated.
* ctDNA is a biomarker of residual cancer disease and could help identify those patients, where completion bowel resection is necessary, sparing those that are already cured.
GOALS ● To explore ctDNA analysis for identification of the patient subgroup with residual disease after local excision of pT1 tumors and hence need for completion resection.
PERSPECTIVES
● Practice-changing evidence for ctDNA-guided risk-stratification for pT1 CRCs after local excision, an important and well-recognized clinical dilemma in the management of CRC.
PROJECT DESCRIPTION After the introduction of the nationwide screening program for CRC in Denmark, the number of very early-stage CRC cases (pT1) has increased. Many of these early cancers present macroscopically as polyps and are removed by local excision. Despite the early detection leading to improved prognosis, locally resected pT1 CRC presents a clinical dilemma, due to the small, but significant, risk of regional lymph node metastasis. This introduces the question: Was the patient cured by local resection alone? - or is segmental bowel resection (termed completion resection) required to remove metastatic regional lymph nodes and cure the patient? The present guideline for managing this clinical situation has led to massive overtreatment. Resection is recommended if the local excision was non-radical or if the histopathological assessment revealed ≥1 histopathological risk factor. However, only 15% of the patients receiving completion resection are diagnosed with metastatic lymph nodes. For the remaining 85%, the local excision was curative, and the completion resection was an overtreatment. Each year in Denmark, 130 colon and 40 rectal completion resections are performed. The complication rate after bowel resection is substantial. Following colonic resections 11% of patients suffer from surgical complications, 7% from medical complications, and 4% from a combination of both. For rectal cancer resection, the corresponding fractions are 20%, 5%, and 5%, respectively. The associated overall 30-day mortality is 1.3%, rising to 1.5% after surgical complications and to 11% after medical or combined complications. Furthermore, many patients suffer from long-term or even chronic postoperative morbidities and late organ effects such as pain, bowel obstruction, and hernia formation.
This highlights the significant importance of accurately choosing patients who indeed require completion resection for a definite cure.
In the current study the use of ctDNA will be explored for identification of the patient subgroup with residual disease after local excision of pT1 tumors and, hence, the need for completion resection.
The hypotheses are (1) ctDNA can be used to identify patients with residual disease requiring completion resection and (2) patients without detectable ctDNA were cured by the local resection, and therefore can be spared completion resection.
Investigators will conduct a prospective, observational feasibility study, assessing the association between pre-completion-resection ctDNA status and the presence of residual disease established by pathological evaluation of the resected specimen. A total of 67 patients, who have undergone local resection of pT1 CRC and who are planned to receive a completion resection will be included. Blood samples will be collected before the completion resection. Tumor tissue will be obtained from the locally resected pT1 tumor.
ctDNA analysis will be performed using the recently published whole genome sequencing-based MRDetect approach.
Feasibility measures: 1) recruitment of \>30 patients every 6 months, 2) a ctDNA positivity rate ≥70%, and 3) accuracy of ctDNA status predicting lymph node status. Using the pathology evaluation of the completion resection specimen as gold standard.
If the performance criteria are met, the study will be transitioned into an open-label 1:1 randomized trial comparing the effect of ctDNA-guided patient selection for completion resection to current practice, which is completion resection to all. If the performance criteria are not met, the method will be re-evaluated to optimize sensitivity.
* 85% of patients receiving completion bowel resection after local removal of pT1 CRC are overtreated.
* ctDNA is a biomarker of residual cancer disease and could help identify those patients, where completion bowel resection is necessary, sparing those that are already cured.
GOALS ● To explore ctDNA analysis for identification of the patient subgroup with residual disease after local excision of pT1 tumors and hence need for completion resection.
PERSPECTIVES
● Practice-changing evidence for ctDNA-guided risk-stratification for pT1 CRCs after local excision, an important and well-recognized clinical dilemma in the management of CRC.
PROJECT DESCRIPTION After the introduction of the nationwide screening program for CRC in Denmark, the number of very early-stage CRC cases (pT1) has increased. Many of these early cancers present macroscopically as polyps and are removed by local excision. Despite the early detection leading to improved prognosis, locally resected pT1 CRC presents a clinical dilemma, due to the small, but significant, risk of regional lymph node metastasis. This introduces the question: Was the patient cured by local resection alone? - or is segmental bowel resection (termed completion resection) required to remove metastatic regional lymph nodes and cure the patient? The present guideline for managing this clinical situation has led to massive overtreatment. Resection is recommended if the local excision was non-radical or if the histopathological assessment revealed ≥1 histopathological risk factor. However, only 15% of the patients receiving completion resection are diagnosed with metastatic lymph nodes. For the remaining 85%, the local excision was curative, and the completion resection was an overtreatment. Each year in Denmark, 130 colon and 40 rectal completion resections are performed. The complication rate after bowel resection is substantial. Following colonic resections 11% of patients suffer from surgical complications, 7% from medical complications, and 4% from a combination of both. For rectal cancer resection, the corresponding fractions are 20%, 5%, and 5%, respectively. The associated overall 30-day mortality is 1.3%, rising to 1.5% after surgical complications and to 11% after medical or combined complications. Furthermore, many patients suffer from long-term or even chronic postoperative morbidities and late organ effects such as pain, bowel obstruction, and hernia formation.
This highlights the significant importance of accurately choosing patients who indeed require completion resection for a definite cure.
In the current study the use of ctDNA will be explored for identification of the patient subgroup with residual disease after local excision of pT1 tumors and, hence, the need for completion resection.
The hypotheses are (1) ctDNA can be used to identify patients with residual disease requiring completion resection and (2) patients without detectable ctDNA were cured by the local resection, and therefore can be spared completion resection.
Investigators will conduct a prospective, observational feasibility study, assessing the association between pre-completion-resection ctDNA status and the presence of residual disease established by pathological evaluation of the resected specimen. A total of 67 patients, who have undergone local resection of pT1 CRC and who are planned to receive a completion resection will be included. Blood samples will be collected before the completion resection. Tumor tissue will be obtained from the locally resected pT1 tumor.
ctDNA analysis will be performed using the recently published whole genome sequencing-based MRDetect approach.
Feasibility measures: 1) recruitment of \>30 patients every 6 months, 2) a ctDNA positivity rate ≥70%, and 3) accuracy of ctDNA status predicting lymph node status. Using the pathology evaluation of the completion resection specimen as gold standard.
If the performance criteria are met, the study will be transitioned into an open-label 1:1 randomized trial comparing the effect of ctDNA-guided patient selection for completion resection to current practice, which is completion resection to all. If the performance criteria are not met, the method will be re-evaluated to optimize sensitivity.
Detailed Description:
KEY POINTS
85 of patients receiving completion bowel resection after local removal of pT1 CRC are overtreated
ctDNA is a biomarker of residual cancer disease and could help identify those patients where completion bowel resection is necessary sparing those that are already cured
GOALS To explore ctDNA analysis for identification of the patient subgroup with residual disease after local excision of pT1 tumors and hence need for completion resection
PERSPECTIVES
Practice-changing evidence for ctDNA-guided risk-stratification for pT1 CRCs after local excision an important and well-recognized clinical dilemma in the management of CRC
PROJECT DESCRIPTION After the introduction of the nationwide screening program for CRC in Denmark the number of very early-stage CRC cases pT1 has increased Many of these early cancers present macroscopically as polyps and are removed by local excision Despite the early detection leading to improved prognosis locally resected pT1 CRC presents a clinical dilemma due to the small but significant risk of regional lymph node metastasis This introduces the question Was the patient cured by local resection alone - or is segmental bowel resection termed completion resection required to remove metastatic regional lymph nodes and cure the patient The present guideline for managing this clinical situation has led to massive overtreatment Resection is recommended if the local excision was non-radical or if the histopathological assessment revealed 1 histopathological risk factor However only 15 of the patients receiving completion resection are diagnosed with metastatic lymph nodes For the remaining 85 the local excision was curative and the completion resection was an overtreatment Each year in Denmark 130 colon and 40 rectal completion resections are performed The complication rate after bowel resection is substantial Following colonic resections 11 of patients suffer from surgical complications 7 from medical complications and 4 from a combination of both For rectal cancer resection the corresponding fractions are 20 5 and 5 respectively The associated overall 30-day mortality is 13 rising to 15 after surgical complications and to 11 after medical or combined complications Furthermore many patients suffer from long-term or even chronic postoperative morbidities and late organ effects such as pain bowel obstruction and hernia formation
This highlights the significant importance of accurately choosing patients who indeed require completion resection for a definite cure
In the current study the use of ctDNA will be explored for identification of the patient subgroup with residual disease after local excision of pT1 tumors and hence the need for completion resection
The hypotheses are 1 ctDNA can be used to identify patients with residual disease requiring completion resection and 2 patients without detectable ctDNA were cured by the local resection and therefore can be spared completion resection
Investigators will conduct a prospective observational feasibility study assessing the association between pre-completion-resection ctDNA status and the presence of residual disease established by pathological evaluation of the resected specimen A total of 67 patients who have undergone local resection of pT1 CRC and who are planned to receive a completion resection will be included Blood samples will be collected before the completion resection Tumor tissue will be obtained from the locally resected pT1 tumor
ctDNA analysis will be performed using the recently published whole genome sequencing-based MRDetect approach
Feasibility measures 1 recruitment of 30 patients every 6 months 2 a ctDNA positivity rate 70 and 3 accuracy of ctDNA status predicting lymph node status Using the pathology evaluation of the completion resection specimen as gold standard
If the performance criteria are met the study will be transitioned into an open-label 11 randomized trial comparing the effect of ctDNA-guided patient selection for completion resection to current practice which is completion resection to all If the performance criteria are not met the method will be re-evaluated to optimize sensitivity
85 of patients receiving completion bowel resection after local removal of pT1 CRC are overtreated
ctDNA is a biomarker of residual cancer disease and could help identify those patients where completion bowel resection is necessary sparing those that are already cured
GOALS To explore ctDNA analysis for identification of the patient subgroup with residual disease after local excision of pT1 tumors and hence need for completion resection
PERSPECTIVES
Practice-changing evidence for ctDNA-guided risk-stratification for pT1 CRCs after local excision an important and well-recognized clinical dilemma in the management of CRC
PROJECT DESCRIPTION After the introduction of the nationwide screening program for CRC in Denmark the number of very early-stage CRC cases pT1 has increased Many of these early cancers present macroscopically as polyps and are removed by local excision Despite the early detection leading to improved prognosis locally resected pT1 CRC presents a clinical dilemma due to the small but significant risk of regional lymph node metastasis This introduces the question Was the patient cured by local resection alone - or is segmental bowel resection termed completion resection required to remove metastatic regional lymph nodes and cure the patient The present guideline for managing this clinical situation has led to massive overtreatment Resection is recommended if the local excision was non-radical or if the histopathological assessment revealed 1 histopathological risk factor However only 15 of the patients receiving completion resection are diagnosed with metastatic lymph nodes For the remaining 85 the local excision was curative and the completion resection was an overtreatment Each year in Denmark 130 colon and 40 rectal completion resections are performed The complication rate after bowel resection is substantial Following colonic resections 11 of patients suffer from surgical complications 7 from medical complications and 4 from a combination of both For rectal cancer resection the corresponding fractions are 20 5 and 5 respectively The associated overall 30-day mortality is 13 rising to 15 after surgical complications and to 11 after medical or combined complications Furthermore many patients suffer from long-term or even chronic postoperative morbidities and late organ effects such as pain bowel obstruction and hernia formation
This highlights the significant importance of accurately choosing patients who indeed require completion resection for a definite cure
In the current study the use of ctDNA will be explored for identification of the patient subgroup with residual disease after local excision of pT1 tumors and hence the need for completion resection
The hypotheses are 1 ctDNA can be used to identify patients with residual disease requiring completion resection and 2 patients without detectable ctDNA were cured by the local resection and therefore can be spared completion resection
Investigators will conduct a prospective observational feasibility study assessing the association between pre-completion-resection ctDNA status and the presence of residual disease established by pathological evaluation of the resected specimen A total of 67 patients who have undergone local resection of pT1 CRC and who are planned to receive a completion resection will be included Blood samples will be collected before the completion resection Tumor tissue will be obtained from the locally resected pT1 tumor
ctDNA analysis will be performed using the recently published whole genome sequencing-based MRDetect approach
Feasibility measures 1 recruitment of 30 patients every 6 months 2 a ctDNA positivity rate 70 and 3 accuracy of ctDNA status predicting lymph node status Using the pathology evaluation of the completion resection specimen as gold standard
If the performance criteria are met the study will be transitioned into an open-label 11 randomized trial comparing the effect of ctDNA-guided patient selection for completion resection to current practice which is completion resection to all If the performance criteria are not met the method will be re-evaluated to optimize sensitivity
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None