Development and Validation of The Post-RT LARS Prediction Model (PORTLARS) (PORTLARS)

Development and Validation of a Nomogram to Predict Severe Bowel Dysfunction After Rectal Cancer Resection and Neoadjuvant Radiotherapy: A Multicenter, Observational Clinical Study

Bowel dysfunction is common after a restorative rectal cancer resection. Neoadjuvant radiotherapy is an influential factor that impairs bowel function and quality of life. However, almost half patients who have received primary surgery with preoperative radiotherapy are able to restore a good or moderate bowel function in the long term. This multicenter observational study aims to identify the risk factors of severe bowel dysfunction after rectal cancer resection and neoadjuvant radiotherapy, in accordance with the LARS score, and to build a model that predicts long-term major LARS in the early stage of follow-up. Development and validation cohorts are enrolled from tertiary hospitals in China.

Study Overview

• Status: Completed
• Conditions: Low Anterior Resection Syndrome; Rectal Cancer; Radiotherapy
• Intervention / Treatment: Other: Questionnaire

• Study Type: Observational
• Enrollment (Actual): 901

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Sixth Affiliated Hospital, Sun Yat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients who underwent preoperative radiotherapy and curative low anterior resection for nonmetastatic rectal cancer.

Description

Inclusion Criteria:

• Curative low anterior resection for nonmetastatic rectal cancer
• Preoperative radiotherapy

Exclusion Criteria:

• Death
• Metastasis or recurrence
• Postoperative radiotherapy
• Cognitive disorder
• Intestinal stoma
• Rectal cancer resection for <12 months
• Stoma reversal for <6 months

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Development; A primary cohort of eligible patients from the Sixth Affiliated Hospital of Sun Yat-sen University is used for model derivation.	Other: Questionnaire; The LARS score is used for assessment of bowel dysfunction after rectal cancer resection.
Internal cross-validation; A cohort of consecutive patients from the Sixth Affiliated Hospital of Sun Yat-sen University is used for internal cross-validation.	Other: Questionnaire; The LARS score is used for assessment of bowel dysfunction after rectal cancer resection.
External validation; An independent cohort of eligible patients from other hospitals is used for external validation.	Other: Questionnaire; The LARS score is used for assessment of bowel dysfunction after rectal cancer resection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve (AUC)	The AUC of PORTLARS in predicting major bowel dysfunction after restorative rectal cancer resection with neoadjuvant radiotherapy. The AUC is evaluated by calculating the area under curve of receiver operating characteristics which plots the proportion of true positive cases (sensitivity) against the proportion of false positive cases (1-specificity) based on various predictive probability threshold.	Over one year after restorative rectal cancer resection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity	The sensitivity of PORTLARS in predicting major bowel dysfunction after restorative rectal cancer resection with neoadjuvant radiotherapy. Model sensitivity is evaluated by calculating the proportion of the 'predicted major LARS' subjects among the total 'actual major LARS' subjects.	Over one year after restorative rectal cancer resection
Specificity	The specificity of PORTLARS in predicting major bowel dysfunction after restorative rectal cancer resection with neoadjuvant radiotherapy. Model specificity is evaluated by calculating the proportion of the 'predicted no/minor LARS' subjects among the total 'actual no/minor LARS' subjects.	Over one year after restorative rectal cancer resection
Positive prediction value (PPV)	The PPV of PORTLARS in predicting major bowel dysfunction after restorative rectal cancer resection with neoadjuvant radiotherapy. Model PPV is evaluated by calculating the proportion of the 'actual major LARS' subjects among the total 'predicted major LARS' subjects.	Over one year after restorative rectal cancer resection
Negative prediction value (NPV)	The NPV of PORTLARS in predicting major bowel dysfunction after restorative rectal cancer resection with neoadjuvant radiotherapy. Model NPV is evaluated by calculating the proportion of the 'actual no/minor LARS' subjects among the total 'predicted no/minor LARS' subjects.	Over one year after restorative rectal cancer resection

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Net reclassification index (NRI)	The additive NRI of PORTLARS compared to other models is evaluated by calculating the percentage of the 'actual major LARS' subjects correctly reclassified to the percentage of the 'actual no/minor LARS' subjects who are correctly reclassified.	Over one year after restorative rectal cancer resection

Collaborators and Investigators

• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University
• Collaborators: Beijing Friendship Hospital; Peking University Cancer Hospital & Institute
• Investigators: Principal Investigator: Qiyuan Qin, M.D., Sixth Affiliated Hospital, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 6, 2020
• Primary Completion (ACTUAL): October 31, 2022
• Study Completion (ACTUAL): October 31, 2022

Study Registration Dates

• First Submitted: November 15, 2021
• First Submitted That Met QC Criteria: November 15, 2021
• First Posted (ACTUAL): November 22, 2021

Study Record Updates

• Last Update Posted (ACTUAL): November 30, 2022
• Last Update Submitted That Met QC Criteria: November 25, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Radiotherapy; Rectal Cancer; Low Anterior Resection Syndrome; Bowel Dysfunction
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: E2020016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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