Rectal Cancer Patients
Conditions
Keywords
circulating tumor cells, liquid biopsy, neoadjuvant chemoradiotherapy, prognostic biomarkers, rectal cancer, surgical resection
Brief summary
This prospective, multi-centre, randomised clinical trial aims to compare the effect of neoadjuvant chemoradiotherapy versus primary surgery on circulating tumor cells (CTCs) in patients with stage II-III rectal cancer without circumferential resection mar-gin involvement. CTCs are considered a promising biomarker for disease dissemination and treatment response. Patients will be randomized to either primary surgical resection with total mesorectal excision or long-course neoadjuvant chemoradiotherapy followed by surgery. Serial blood samples will be collected at predefined time points to assess the presence and dynamics of CTCs. Secondary endpoints include perioperative morbidity and mortality, local recurrence rate, disease-free survival, and overall survival. The results of this study may provide new insights into the prognostic role of CTCs and contribute to optimising treatment strategies for rectal cancer.
Detailed description
Colorectal cancer remains one of the most common malignancies worldwide, and rectal cancer requires a multidisciplinary treatment approach. For patients with locally advanced rectal cancer, neoadjuvant chemoradiotherapy (nCRT) followed by surgical resection has been widely used to reduce the risk of local recurrence. However, the indication for nCRT in patients without circumferential resection margin (CRM) involvement remains controversial. While some studies have suggested benefits of nCRT, others have shown comparable oncological outcomes with primary surgery when high-quality total mesorectal excision (TME) is performed. Circulating tumor cells (CTCs) are malignant cells detectable in peripheral blood that have been associated with metastatic potential and poor prognosis in various cancers, including colorectal cancer. Monitoring the presence and dynamics of CTCs offers a minimally invasive liquid biopsy approach that may provide prognostic information and reflect treatment efficacy. Existing evidence suggests that changes in CTC levels after surgery or systemic therapy may correlate with recurrence risk and survival, but relevant data in rectal cancer patients undergoing multimodal treatment are limited. This prospective, multi-centre, randomised clinical trial will enrol patients with stage II-III rectal cancer without evidence of CRM involvement on staging magnetic resonance imaging (MRI). Eligible patients will be randomized into two study arms: 1. Primary surgery arm: radical surgical resection with total mesorectal excision (TME). 2. Neoadjuvant therapy arm: long-course neoadjuvant chemoradiotherapy fol-lowed by delayed surgical resection. Peripheral blood samples will be collected at predefined time points in both groups to determine the presence and quantity of CTCs. The primary objective is to compare the effect of neoadjuvant chemoradiotherapy versus surgery alone on CTC dynamics. Secondary objectives include: * Evaluation of short-term surgical outcomes (perioperative complications, 30-day morbidity and mortality). * Assessment of long-term oncological outcomes (local recurrence, disease-free survival, and overall survival at 3 and 5 years). By integrating CTC monitoring into a modern randomized clinical trial design, this study aims to clarify the prognostic value of CTCs in rectal cancer and determine whether specific treatment strategies are associated with more favourable biological and clinical outcomes. The findings may contribute to more individualised treatment planning and potentially reduce the risk of recurrence and mortality in rectal cancer patients.
Interventions
PROCEDUREPrimary Surgery
Patients undergo radical surgical resection with TME without preceding neoadjuvant therapy
PROCEDURENeoadjuvant radiochemotherapy and surgery
Neoadjuvant treatment: long-course pelvic radiotherapy (conventional fractionation) with concurrent chemotherapy (standard fluoropyrimidine-based regimen)
Sponsors
University Hospital Ostrava
Palacky University
University Hospital Olomouc
Municipal Hospital Ostrava
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Histologically confirmed rectal adenocarcinoma within 12 cm from anal verge * Stage II (cT3-4 N0 M0) or stage III (cT1-4 N1-2, M0) * Negative circumferential resection margin on staging MRI * ASA physical status I-III * Signed informed consent
Exclusion criteria
* Tumor infiltration beyond fascia recti propria on MRI * Metastatic disease (stage IV) * Recurrent rectal cancer * Other concurrent malignancies * Emergency surgery required * Contraindication to surgery under general anesthesia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Circulating Tumor Cells (CTC) Dynamics - primary surgery - CD45 negativity | (1) preoperatively (1-2 weeks before surgery), (2) 1 week postoperatively, and (3) 1 month postoperatively | The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The presence of CD45 negativity in CTCs will be observed. CD45 negative means a cell does not express the CD45 protein on its surface. |
| Circulating Tumor Cells (CTC) Dynamics - neoadjuvant treatment - pancytokeratin and/or EpCAM positivity | (1) before the initiation of CRT, (2) 1 week and (3) 1 month after the initiation of CRT, (4) preoperatively (1-2 weeks before surgery), (5) 1 week postoperatively, and (6) 1 month postoperatively | The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The presence of pancytokeratin and/or EpCAM positivity in CTCs will be observed. EpCAM positivity refers to the presence of EpCAM (Epithelial Cell Adhesion Molecule) protein on cells, which is a marker primarily expressed on epithelial cells and in many carcinomas. |
| Circulating Tumor Cells (CTC) Dynamics - neoadjuvant treatment - CD45 negativity | (1) before the initiation of CRT, (2) 1 week and (3) 1 month after the initiation of CRT, (4) preoperatively (1-2 weeks before surgery), (5) 1 week postoperatively, and (6) 1 month postoperatively | The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The presence of CD45 negativity in CTCs will be observed. CD45 negative means a cell does not express the CD45 protein on its surface. |
| Circulating Tumor Cells (CTC) Dynamics - primary surgery - shape | (1) preoperatively (1-2 weeks before surgery), (2) 1 week postoperatively, and (3) 1 month postoperatively | The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The presence of CTC round shape will be observed. |
| Circulating Tumor Cells (CTC) Dynamics - primary surgery - size | (1) preoperatively (1-2 weeks before surgery), (2) 1 week postoperatively, and (3) 1 month postoperatively | The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The CTC size will be observed, with the border value of \> 4 μm. |
| Circulating Tumor Cells (CTC) Dynamics - primary surgery - DAPI positivity | (1) preoperatively (1-2 weeks before surgery), (2) 1 week postoperatively, and (3) 1 month postoperatively | The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The DAPI positivity will be observed. A DAPI-positive nucleus is a cell nucleus that has been stained with DAPI (4',6-diamidino-2-phenylindole), a fluorescent dye that binds specifically to the adenine-thymine (A-T) rich regions of double-stranded DNA. |
| Circulating Tumor Cells (CTC) Dynamics - primary surgery - pancytokeratin and/or EpCAM positivity | (1) preoperatively (1-2 weeks before surgery), (2) 1 week postoperatively, and (3) 1 month postoperatively | The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The presence of pancytokeratin and/or EpCAM positivity in CTCs will be observed. EpCAM positivity refers to the presence of EpCAM (Epithelial Cell Adhesion Molecule) protein on cells, which is a marker primarily expressed on epithelial cells and in many carcinomas. |
| Circulating Tumor Cells (CTC) Dynamics - neoadjuvant treatment - shape | (1) before the initiation of CRT, (2) 1 week and (3) 1 month after the initiation of CRT, (4) preoperatively (1-2 weeks before surgery), (5) 1 week postoperatively, and (6) 1 month postoperatively | The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The presence of CTC round shape will be observed. |
| Circulating Tumor Cells (CTC) Dynamics - neoadjuvant treatment - size | (1) before the initiation of CRT, (2) 1 week and (3) 1 month after the initiation of CRT, (4) preoperatively (1-2 weeks before surgery), (5) 1 week postoperatively, and (6) 1 month postoperatively | The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The CTC size will be observed, with the border value of \> 4 μm. |
| Circulating Tumor Cells (CTC) Dynamics - neoadjuvant treatment - DAPI positivity | (1) before the initiation of CRT, (2) 1 week and (3) 1 month after the initiation of CRT, (4) preoperatively (1-2 weeks before surgery), (5) 1 week postoperatively, and (6) 1 month postoperatively | The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The DAPI positivity will be observed. A DAPI-positive nucleus is a cell nucleus that has been stained with DAPI (4',6-diamidino-2-phenylindole), a fluorescent dye that binds specifically to the adenine-thymine (A-T) rich regions of double-stranded DNA. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Short-term postoperative outcomes - 30-day morbidity | Within 30 days after surgery | 30-day morbidity will be observed |
| Short-term postoperative outcomes - 30-day mortality | Within 30 days after surgery | 30-day mortality will be observed |
| Local recurrence rate | Up to 5 years | Cumulative incidence of local tumor recurrence after treatment. |
| Disease-free survival (DFS) | 3 and 5 years after surgery | Interval from treatment to recurrence, progression, or death. |
| Overall survival (OS) | 3 and 5 years after surgery | Proportion of patients alive at 3 and 5 years. |
| Short-term postoperative outcomes - preoperative complications | Within 30 days after surgery | The occurrence of perioperative complications will be observed |
Countries
Czechia
Contacts
Primary ContactJiří Hynčica
Outcome results
None listed