xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05964530</url>
    </required_header>
    <id_info>
      <org_study_id>202212114RIND</org_study_id>
      <nct_id>NCT05964530</nct_id>
    </id_info>
    <brief_title>Radical vs Local Excision for Rectal Cancer With Clinically Complete Remission</brief_title>
    <official_title>Comparing the Oncologic Efficacy of Radical Versus Local Excision for Rectal Cancer With Clinically Complete Remission to Neoadjuvant Chemoradiation Therapy: A Randomized Controlled Clinical Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>National Taiwan University Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>National Taiwan University Hospital</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        In the present project, the investigators plan to more accurately select the rectal cancer&#xD;
        patients with pathological complete response (pCR) to preoperative concomitant chemoradiation&#xD;
        therapy (CCRT), taking advantage of quantification of circulating tumor DNA (ctDNA) in&#xD;
        addition to the current available diagnostic modalities, including CT, MRI, PET and&#xD;
        colonoscopy. The patients with suspected pCR to CCRT will be randomized to radical surgery&#xD;
        and local excision groups, followed by the comparison of the oncologic outcomes between two&#xD;
        treatment methods. The investigators hypothesized that if the pCR for patients with rectal&#xD;
        cancer after CCRT can be more accurately predicted, such patients can be safely treated with&#xD;
        limited surgery to enhance the post-treatment life quality, in comparison with patients&#xD;
        undergoing radical surgery.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        In Taiwan, patients with stage Ⅱ or Ⅲ rectal cancer represented around 30% of all cases of&#xD;
        colorectal cancer(n=15,000 annually). Standard treatment of locally advanced rectal cancer&#xD;
        consists of neoadjuvant chemoradiotherapy (nCRT), total mesorectal excision (TME), and&#xD;
        postoperative adjuvant chemotherapy. This intensive treatment leads to good local tumor&#xD;
        control and patient survival, but is associated with short- and long-term morbidity that&#xD;
        impairs each patient's quality of life permanently. Although nCRT followed by adjuvant&#xD;
        chemotherapy are associated with specific toxicity and may compound surgery-related&#xD;
        morbidity, most of the side effects of multimodal treatment that impair the patient's quality&#xD;
        of life are attributable to TME with sphincter-preservation or abdomino-perineal resection&#xD;
        (APR). Even with the technological advances of robotic and transanal TME, some patients with&#xD;
        distal rectal cancer will still require a permanent colostomy. In addition, patients who&#xD;
        undergo a sphincter-saving procedure develop a combination of defecatory symptoms known as&#xD;
        low anterior resection syndrome. These symptoms are associated with significant impairment of&#xD;
        patients' quality of life. With the age-adjusted incidence of rectal cancer increasing&#xD;
        steadily in young patients, alternatives to TME are needed.&#xD;
  &#xD;
        Some patients with locally advanced rectal cancer have a pathological complete response (pCR)&#xD;
        to nCRT. Because patients with pCR have excellent prognosis,8 surgeons question the added&#xD;
        value of TME for patients with a clinical complete response (cCR) to CRT. Several&#xD;
        institutional case series have reported that a watch-and-wait strategy can result in&#xD;
        sustained organ preservation in patients with a cCR to nCRT. Remarkably, up to 30% of&#xD;
        patients entered in watch-and-wait protocols eventually experienced tumor re-growth, but most&#xD;
        of the cases were surgically salvageable.9 In some series, the survival rate in patients with&#xD;
        clinical complete response (cCR) entered in a watch-and-wait protocol was equivalent to that&#xD;
        in patients found to have a pCR after TME. However, most of these series, recently published&#xD;
        together as an international multicenter registry study, are heterogeneous in terms of tumor&#xD;
        stages, radiation dosage, sensitizing chemotherapy, the criteria and timing for assessment of&#xD;
        response, and surveillance follow-up protocols. Because these series included only selected&#xD;
        patients entering in the watch-and-wait protocol without reporting the total number of&#xD;
        patients with similar-stage rectal tumors treated with neoadjuvant therapy during the study&#xD;
        period, the possibility of selection bias cannot be excluded. Without a reference&#xD;
        denominator, the number of patients who would have potentially benefited from organ&#xD;
        preservation by using a watch-and-wait strategy is unknown.&#xD;
  &#xD;
        With above-mentioned reasons, most of the patients, including the international case series&#xD;
        and our previous case reports, still receive radical surgery for their rectal cancer with cCR&#xD;
        to neoadjuvant CRT; some patients with cCR even received a theoretically unnecessary APR&#xD;
        procedure and wore a colostoma for life. To enhance the life quality for such patients with&#xD;
        cCR to nCRT, the guidelines of the National Comprehensive Cancer Network for treatment of&#xD;
        rectal cancer included total neoadjuvant therapy (TNT; systemic chemotherapy before rather&#xD;
        than after TME), which was developed in part as a strategy to increase the rate of tumor&#xD;
        response. However, to date, the impact of TNT on the potential for organ preservation through&#xD;
        avoidance of surgery is unknown.&#xD;
  &#xD;
        There is no denying that the organ preservation with no immediate surgery, i.e., the&#xD;
        watch-and-wait strategy, in selected patients with a cCR after nCRT is currently at the&#xD;
        forefront of rectal cancer management. This strategy is considered as an attractive option to&#xD;
        avoid major surgery and the associated morbidity and mortality risks, and functional&#xD;
        consequences. However, with the watch-and-wait approach, there is a risk for the development&#xD;
        of local regrowth, systemic recurrence, or both, despite the initial achievement of a&#xD;
        clinical complete response. Overall, the risk of local re-growth within 3 years from&#xD;
        attaining a clinical complete response is 25-30%, and even the occurrence of local re-growth&#xD;
        at as long as 7 years from the completion of neoadjuvant chemoradiotherapy has been reported.&#xD;
        Therefore, long-term and intensive surveillance protocols have been recommended for patients&#xD;
        managed by a watch-and-wait strategy. Remarkably, in consideration of the watch-and-wait&#xD;
        policy requires intensive medical resources, it has been not adopted in Taiwan and most of&#xD;
        the centers of excellence worldwide.&#xD;
  &#xD;
        On the other hand, the GRECCAR2 multicenter randomized trial showed that no evidence of&#xD;
        difference in oncological outcomes between local excision and total mesorectal excision in&#xD;
        term of 5-year overall survival. Local excision can be proposed in selected patients having a&#xD;
        small T2-T3 low rectal cancer with a good clinical response after chemoradiotherapy. However,&#xD;
        their study subjects were not limited to rectal cancer with cCR to preoperative CCRT.&#xD;
  &#xD;
        The investigators believe that local excision can be applied to the highly selective patients&#xD;
        with rectal cancer, especially those with cCR to operative CCRT. However, up to date, there&#xD;
        is still no diagnostics to accurately predict the pCR of the rectal cancer to CCRT. And&#xD;
        therefore, both the colorectal surgeons and patients has been receiving radical surgery as&#xD;
        the major treatment modality. Remarkably, with advent of genetic technology, it become&#xD;
        feasible to utilize ctDNA for predicting the response to neoadjuvant chemoradiotherapy and&#xD;
        prognosis assessment in locally advanced rectal cancer.&#xD;
  &#xD;
        The ctDNA (mutant allele) has been known to be with an extremely short plasma half-life&#xD;
        (shorter than 2 hours) compared with tumor markers (such as CEA and CA19-9). After curative&#xD;
        resection, therefore, ctDNA rapidly disappears from the blood if no residual cancer exists.&#xD;
        Utilizing these characteristics of ctDNA, a diagnostic system for detecting minimal residual&#xD;
        disease (MRD) using a next generation sequencing technology is being developed. Remarkably,&#xD;
        SignateraTM is a novel ctDNA detection system for MRD detection developed by Natera Inc.,&#xD;
        U.S.A. First, whole exon analysis of tumor tissue samples is performed, followed by&#xD;
        extraction of 16 somatic mutations from the detected tumor-specific single nucleotide&#xD;
        variants using an original program, and the primer set that detects these variants is&#xD;
        established for each patient and tumor. SignateraTM is a test system that extracts ctDNA from&#xD;
        the blood obtained postoperatively, using this primer set, and detects the presence or&#xD;
        absence of somatic mutations derived from tumors using a next generation sequencer. In&#xD;
        SignateraTM, the sensitivity limit for ctDNA allele frequency is 0.005%, the 90% sensitivity&#xD;
        limit is 0.010%, and the specificity is at least 99.5%. In a multicenter prospective cohort&#xD;
        study in patients with Stage I-III colorectal carcinoma, 130 patients with Stage I-III&#xD;
        colorectal carcinoma were enrolled. The ctDNA positive rate at 30 days after the curative&#xD;
        resection was 10.6%, and the relapse rate was 7 times or more higher in the ctDNA positive&#xD;
        group than in the ctDNA negative group (hazard ratio [HR] = 7.2; 95% CI, 2.7-19.0). In&#xD;
        addition, of the 58 patients who were evaluable for ctDNA after completing postoperative&#xD;
        adjuvant chemotherapy, 7 patients (12.0%) were positive for ctDNA, and 51 patients (88.0%)&#xD;
        were negative for ctDNA, with relapse observed in all ctDNA-positive patients, which was&#xD;
        significantly higher than the relapse rate in ctDNA-negative patients (7/51 patients, 13.7%)&#xD;
        (HR = 17.5; 95% CI, 5.4-56.5). Moreover, of the 75 patients who were tested for ctDNA&#xD;
        chronologically, 14 out of 15 ctDNA-positive patients (93.3%) had a relapse, and of the 60&#xD;
        patients who were negative for ctDNA, only 2 patients had a relapse. With respect to&#xD;
        time-to-relapse, the median time to confirmation of a relapse by ordinary CT scan was 14.2&#xD;
        months, while the median time to detection of positive ctDNA was 5.5 months.&#xD;
  &#xD;
        In the present project, the investigators plan to more accurately select the rectal cancer&#xD;
        patients with pCR to preoperative CCRT, taking advantage of quantification of ctDNA in&#xD;
        addition to the current available diagnostic modalities, including CT, MRI, PET and&#xD;
        colonoscopy. The patients with suspected pCR to CCRT will be randomized to radical surgery&#xD;
        and local excision groups, followed by the comparison of the oncologic outcomes between two&#xD;
        treatment methods. The investigators hypothesized that if the pCR for patients with rectal&#xD;
        cancer after CCRT can be more accurately predicted, such patients can be safely treated with&#xD;
        limited surgery to enhance the post-treatment life quality, in comparison with patients&#xD;
        undergoing radical surgery.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">April 19, 2023</start_date>
    <completion_date type="Anticipated">October 19, 2026</completion_date>
    <primary_completion_date type="Anticipated">April 19, 2026</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Single (Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Overall disease-free survival</measure>
      <time_frame>3 years</time_frame>
      <description>The duration from surgical resection of primary tumor to the cancer recurrence</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Postoperative 30-day complications</measure>
      <time_frame>30 days</time_frame>
      <description>Defined as Clavien-Dindo classification. It consists of 7 grades (I, II, IIIa, IIIb, IVa, IVb and V). The class I means no complication, whereas class V means death of the patient.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The length of stay</measure>
      <time_frame>An average of 7 days</time_frame>
      <description>The duration from the time of surgery to the time of leaving the hospital</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival</measure>
      <time_frame>3 years</time_frame>
      <description>The duration from surgical resection of primary tumor to the death due to cancer progression</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">180</enrollment>
    <condition>Rectal Cancer</condition>
    <arm_group>
      <arm_group_label>Watch and wait group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>In this group, the patients with clinically complete response will undergo non-surgical treatment (watch-and-wait group)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Surgical group</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>In this group, the patients with clinically complete response will undergo surgical treatment (LAR with anal preservation or APR)</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Surgery</intervention_name>
      <description>Surgery procedures include LAR+ anal preservation or APR</description>
      <arm_group_label>Surgical group</arm_group_label>
      <arm_group_label>Watch and wait group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. rectal adenocarcinoma completed nCRT and the imaging studies showed no residual&#xD;
               malignancy;&#xD;
  &#xD;
            2. physical status is within American Society of Anesthesiology（ASA）class Ⅰ to Ⅲ;&#xD;
  &#xD;
            3. the lesion side can be reached by the transanal local excision, generally within 6 cm&#xD;
               above anal verge;&#xD;
  &#xD;
            4. age is 18-75 years.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Quantification of ct DNA shows residual malignancy;&#xD;
  &#xD;
            2. Body mass index（BMI）&gt;40 kg/m2;&#xD;
  &#xD;
            3. Previous abdominal or pelvic surgery;&#xD;
  &#xD;
            4. abnormal hepatologic (Bil&gt;2.0 mg/dl), renal (Cre≧2.0) and hematologic(WBC&lt;3000,&#xD;
               HB&lt;8.0, platelet&lt;50000) profiles after CCRT.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Jin-Tung LIANG, MD</last_name>
      <role>Study Director</role>
      <affiliation>National Taiwan University Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Jin-Tung LIANG, MD</last_name>
      <phone>+886-972654554</phone>
      <email>jintung@ntu.edu.tw</email>
    </overall_contact>
    <location>
      <facility>
        <name>Jin-Tung LIANG</name>
        <address>
          <city>Taipei</city>
          <zip>100</zip>
          <country>Taiwan</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Jin-Tung LIANG, MD</last_name>
        <phone>+886972651432</phone>
        <email>jintung@ntu.edu.tw</email>
      </contact>
    </location>
    <location_countries>
      <country>Taiwan</country>
    </location_countries>
    <verification_date>April 2023</verification_date>
    <study_first_submitted>July 17, 2023</study_first_submitted>
    <study_first_submitted_qc>July 27, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 28, 2023</study_first_posted>
    <last_update_submitted>July 27, 2023</last_update_submitted>
    <last_update_submitted_qc>July 27, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">July 28, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Rectal cancer</keyword>
    <keyword>Concomitant chemoradiation therapy</keyword>
    <keyword>Radical surgery</keyword>
    <keyword>Local excision</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Rectal Neoplasms</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05964530
  org study id: 202212114RIND
  nct id: NCT05964530
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  In the present project, the investigators plan to more accurately select the rectal cancer
        patients with pathological complete response (pCR) to preoperative concomitant chemoradiation
        therapy (CCRT), taking advantage of quantification of circulating tumor DNA (ctDNA) in
        addition to the current available diagnostic modalities, including CT, MRI, PET and
        colonoscopy. The patients with suspected pCR to CCRT will be randomized to radical surgery
        and local excision groups, followed by the comparison of the oncologic outcomes between two
        treatment methods. The investigators hypothesized that if the pCR for patients with rectal
        cancer after CCRT can be more accurately predicted, such patients can be safely treated with
        limited surgery to enhance the post-treatment life quality, in comparison with patients
        undergoing radical surgery.
  In Taiwan, patients with stage Ⅱ or Ⅲ rectal cancer represented around 30% of all cases of
        colorectal cancer(n=15,000 annually). Standard treatment of locally advanced rectal cancer
        consists of neoadjuvant chemoradiotherapy (nCRT), total mesorectal excision (TME), and
        postoperative adjuvant chemotherapy. This intensive treatment leads to good local tumor
        control and patient survival, but is associated with short- and long-term morbidity that
        impairs each patient's quality of life permanently. Although nCRT followed by adjuvant
        chemotherapy are associated with specific toxicity and may compound surgery-related
        morbidity, most of the side effects of multimodal treatment that impair the patient's quality
        of life are attributable to TME with sphincter-preservation or abdomino-perineal resection
        (APR). Even with the technological advances of robotic and transanal TME, some patients with
        distal rectal cancer will still require a permanent colostomy. In addition, patients who
        undergo a sphincter-saving procedure develop a combination of defecatory symptoms known as
        low anterior resection syndrome. These symptoms are associated with significant impairment of
        patients' quality of life. With the age-adjusted incidence of rectal cancer increasing
        steadily in young patients, alternatives to TME are needed.
  
        Some patients with locally advanced rectal cancer have a pathological complete response (pCR)
        to nCRT. Because patients with pCR have excellent prognosis,8 surgeons question the added
        value of TME for patients with a clinical complete response (cCR) to CRT. Several
        institutional case series have reported that a watch-and-wait strategy can result in
        sustained organ preservation in patients with a cCR to nCRT. Remarkably, up to 30% of
        patients entered in watch-and-wait protocols eventually experienced tumor re-growth, but most
        of the cases were surgically salvageable.9 In some series, the survival rate in patients with
        clinical complete response (cCR) entered in a watch-and-wait protocol was equivalent to that
        in patients found to have a pCR after TME. However, most of these series, recently published
        together as an international multicenter registry study, are heterogeneous in terms of tumor
        stages, radiation dosage, sensitizing chemotherapy, the criteria and timing for assessment of
        response, and surveillance follow-up protocols. Because these series included only selected
        patients entering in the watch-and-wait protocol without reporting the total number of
        patients with similar-stage rectal tumors treated with neoadjuvant therapy during the study
        period, the possibility of selection bias cannot be excluded. Without a reference
        denominator, the number of patients who would have potentially benefited from organ
        preservation by using a watch-and-wait strategy is unknown.
  
        With above-mentioned reasons, most of the patients, including the international case series
        and our previous case reports, still receive radical surgery for their rectal cancer with cCR
        to neoadjuvant CRT; some patients with cCR even received a theoretically unnecessary APR
        procedure and wore a colostoma for life. To enhance the life quality for such patients with
        cCR to nCRT, the guidelines of the National Comprehensive Cancer Network for treatment of
        rectal cancer included total neoadjuvant therapy (TNT; systemic chemotherapy before rather
        than after TME), which was developed in part as a strategy to increase the rate of tumor
        response. However, to date, the impact of TNT on the potential for organ preservation through
        avoidance of surgery is unknown.
  
        There is no denying that the organ preservation with no immediate surgery, i.e., the
        watch-and-wait strategy, in selected patients with a cCR after nCRT is currently at the
        forefront of rectal cancer management. This strategy is considered as an attractive option to
        avoid major surgery and the associated morbidity and mortality risks, and functional
        consequences. However, with the watch-and-wait approach, there is a risk for the development
        of local regrowth, systemic recurrence, or both, despite the initial achievement of a
        clinical complete response. Overall, the risk of local re-growth within 3 years from
        attaining a clinical complete response is 25-30%, and even the occurrence of local re-growth
        at as long as 7 years from the completion of neoadjuvant chemoradiotherapy has been reported.
        Therefore, long-term and intensive surveillance protocols have been recommended for patients
        managed by a watch-and-wait strategy. Remarkably, in consideration of the watch-and-wait
        policy requires intensive medical resources, it has been not adopted in Taiwan and most of
        the centers of excellence worldwide.
  
        On the other hand, the GRECCAR2 multicenter randomized trial showed that no evidence of
        difference in oncological outcomes between local excision and total mesorectal excision in
        term of 5-year overall survival. Local excision can be proposed in selected patients having a
        small T2-T3 low rectal cancer with a good clinical response after chemoradiotherapy. However,
        their study subjects were not limited to rectal cancer with cCR to preoperative CCRT.
  
        The investigators believe that local excision can be applied to the highly selective patients
        with rectal cancer, especially those with cCR to operative CCRT. However, up to date, there
        is still no diagnostics to accurately predict the pCR of the rectal cancer to CCRT. And
        therefore, both the colorectal surgeons and patients has been receiving radical surgery as
        the major treatment modality. Remarkably, with advent of genetic technology, it become
        feasible to utilize ctDNA for predicting the response to neoadjuvant chemoradiotherapy and
        prognosis assessment in locally advanced rectal cancer.
  
        The ctDNA (mutant allele) has been known to be with an extremely short plasma half-life
        (shorter than 2 hours) compared with tumor markers (such as CEA and CA19-9). After curative
        resection, therefore, ctDNA rapidly disappears from the blood if no residual cancer exists.
        Utilizing these characteristics of ctDNA, a diagnostic system for detecting minimal residual
        disease (MRD) using a next generation sequencing technology is being developed. Remarkably,
        SignateraTM is a novel ctDNA detection system for MRD detection developed by Natera Inc.,
        U.S.A. First, whole exon analysis of tumor tissue samples is performed, followed by
        extraction of 16 somatic mutations from the detected tumor-specific single nucleotide
        variants using an original program, and the primer set that detects these variants is
        established for each patient and tumor. SignateraTM is a test system that extracts ctDNA from
        the blood obtained postoperatively, using this primer set, and detects the presence or
        absence of somatic mutations derived from tumors using a next generation sequencer. In
        SignateraTM, the sensitivity limit for ctDNA allele frequency is 0.005%, the 90% sensitivity
        limit is 0.010%, and the specificity is at least 99.5%. In a multicenter prospective cohort
        study in patients with Stage I-III colorectal carcinoma, 130 patients with Stage I-III
        colorectal carcinoma were enrolled. The ctDNA positive rate at 30 days after the curative
        resection was 10.6%, and the relapse rate was 7 times or more higher in the ctDNA positive
        group than in the ctDNA negative group (hazard ratio [HR] = 7.2; 95% CI, 2.7-19.0). In
        addition, of the 58 patients who were evaluable for ctDNA after completing postoperative
        adjuvant chemotherapy, 7 patients (12.0%) were positive for ctDNA, and 51 patients (88.0%)
        were negative for ctDNA, with relapse observed in all ctDNA-positive patients, which was
        significantly higher than the relapse rate in ctDNA-negative patients (7/51 patients, 13.7%)
        (HR = 17.5; 95% CI, 5.4-56.5). Moreover, of the 75 patients who were tested for ctDNA
        chronologically, 14 out of 15 ctDNA-positive patients (93.3%) had a relapse, and of the 60
        patients who were negative for ctDNA, only 2 patients had a relapse. With respect to
        time-to-relapse, the median time to confirmation of a relapse by ordinary CT scan was 14.2
        months, while the median time to detection of positive ctDNA was 5.5 months.
  
        In the present project, the investigators plan to more accurately select the rectal cancer
        patients with pCR to preoperative CCRT, taking advantage of quantification of ctDNA in
        addition to the current available diagnostic modalities, including CT, MRI, PET and
        colonoscopy. The patients with suspected pCR to CCRT will be randomized to radical surgery
        and local excision groups, followed by the comparison of the oncologic outcomes between two
        treatment methods. The investigators hypothesized that if the pCR for patients with rectal
        cancer after CCRT can be more accurately predicted, such patients can be safely treated with
        limited surgery to enhance the post-treatment life quality, in comparison with patients
        undergoing radical surgery.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Single (Outcomes Assessor)
  measure: Overall disease-free survival
  time frame: 3 years
  description: The duration from surgical resection of primary tumor to the cancer recurrence
  measure: Postoperative 30-day complications
  time frame: 30 days
  description: Defined as Clavien-Dindo classification. It consists of 7 grades (I, II, IIIa, IIIb, IVa, IVb and V). The class I means no complication, whereas class V means death of the patient.
  measure: The length of stay
  time frame: An average of 7 days
  description: The duration from the time of surgery to the time of leaving the hospital
  measure: Overall survival
  time frame: 3 years
  description: The duration from surgical resection of primary tumor to the death due to cancer progression
  arm group label: Watch and wait group
  arm group type: Experimental
  description: In this group, the patients with clinically complete response will undergo non-surgical treatment (watch-and-wait group)
  arm group label: Surgical group
  arm group type: Active Comparator
  description: In this group, the patients with clinically complete response will undergo surgical treatment (LAR with anal preservation or APR)
  intervention type: Procedure
  intervention name: Surgery
  description: Surgery procedures include LAR+ anal preservation or APR
  arm group label: Surgical group
  arm group label: Watch and wait group
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Jin-Tung LIANG, MD
  role: Study Director
  affiliation: National Taiwan University Hospital
  last name: Jin-Tung LIANG, MD
  phone: +886-972654554
  email: jintung@ntu.edu.tw
  facility: 
  status: Recruiting
  contact: 
  country: Taiwan
  responsible party type: Sponsor
  mesh term: Rectal Neoplasms