Multicentric National Italian Analysis of Textbook Outcome in Colorectal Cancer Surgery

Background and Rationale Colorectal cancer (CRC) is the third most commonly diagnosed malignancy worldwide and remains one of the leading causes of cancer-related mortality despite substantial advances in prevention, diagnosis, surgical techniques, perioperative care, and systemic therapies. Although improvements in multidisciplinary management have significantly enhanced postoperative and oncological outcomes, considerable variability in the quality of surgical care persists across institutions and healthcare systems. Such variability reflects differences in patient selection, perioperative management, surgical expertise, institutional organization, and adherence to evidence-based practices rather than differences in disease biology alone. Traditionally, hospital performance has been assessed using isolated outcome measures such as postoperative mortality, complication rates, length of hospital stay, or oncological adequacy of resection. However, these individual metrics provide only a partial representation of the overall quality of surgical care because they evaluate single components of a patient's perioperative course rather than the entire clinical pathway. Composite quality measures have therefore emerged as more comprehensive indicators of healthcare performance by integrating multiple clinically relevant outcomes into a single patient-centered endpoint. Among these composite measures, Textbook Outcome (TO) has become increasingly recognized as one of the most robust indicators of surgical quality. Rather than evaluating isolated events, TO represents the achievement of an ideal postoperative course in which all predefined quality criteria are simultaneously fulfilled. Failure to satisfy even one component results in failure to achieve TO, making it a stringent measure of overall quality of care. This approach better reflects the multidimensional nature of perioperative management and emphasizes that optimal surgical care requires excellence throughout the entire patient journey. In colorectal cancer surgery, TO incorporates essential indicators of oncological adequacy, postoperative recovery, and surgical safety. Previous studies have demonstrated that patients achieving TO experience superior short-term outcomes and improved long-term survival compared with those who fail to achieve this composite endpoint. Furthermore, TO has been proposed as an institutional quality benchmark capable of identifying unwarranted variation in surgical performance across hospitals. Nevertheless, important heterogeneity remains regarding its definition, implementation, and clinical application, limiting comparisons among healthcare systems and reducing its potential use as a standardized quality indicator. Recent international efforts have attempted to harmonize the definition of TO in colorectal surgery through expert consensus. While consensus methodologies provide valuable guidance, they are inherently based on expert opinion and may not fully capture the complexity and variability of routine clinical practice. Validation using large real-world datasets remains essential to determine whether proposed definitions accurately reflect contemporary surgical outcomes and can serve as reliable benchmarks for quality assessment. The Analysis of Textbook Outcome in Colorectal Cancer Surgery (ATOCCS) study has been designed to address this knowledge gap through a large nationwide multicenter observational cohort conducted on behalf of the Italian Association of Hospital Surgeons (ACOI). By collecting standardized data from multiple Italian surgical units, the study seeks to evaluate the applicability of TO in routine clinical practice, quantify its incidence, identify determinants of TO failure, and investigate the relationship between TO achievement and clinically meaningful postoperative outcomes. Beyond evaluating individual patient outcomes, ATOCCS aims to establish a robust national benchmark for colorectal cancer surgery by exploring inter-hospital variability and identifying opportunities for quality improvement. The study is expected to generate real-world evidence supporting the implementation of standardized quality indicators capable of complementing traditional volume-based assessments and contributing to future national quality assessment programs. Because of its large multicenter design, standardized data collection, and comprehensive evaluation of perioperative outcomes, the ATOCCS study represents one of the largest contemporary investigations of Textbook Outcome in colorectal cancer surgery and is expected to provide evidence supporting its use as a clinically meaningful, reproducible, and patient-centered measure of surgical quality. Study Objectives and Study Design The Analysis of Textbook Outcome in Colorectal Cancer Surgery (ATOCCS) is a national, multicenter, retrospective observational cohort study designed to evaluate the quality of surgical care delivered to patients undergoing curative-intent colorectal cancer resection in Italy. The study is conducted on behalf of the Italian Association of Hospital Surgeons (ACOI) and involves a collaborative network of Italian surgical departments representing different institutional settings and surgical practice environments. By adopting standardized definitions, harmonized data collection procedures, and uniform outcome measures, the study aims to generate a comprehensive national assessment of Textbook Outcome (TO) in contemporary colorectal cancer surgery. Primary Objective The primary objective is to determine the proportion of patients achieving a Textbook Outcome following curative colorectal cancer surgery according to a predefined composite quality metric. For the purpose of this study, TO is defined as the simultaneous achievement of all six of the following criteria: survival within 30 days after surgery; R0 resection with examination of at least 12 lymph nodes; absence of major postoperative complications (Clavien-Dindo grade III or higher); absence of unplanned reintervention; absence of unplanned stoma formation; postoperative hospital stay of 14 days or less without unplanned readmission. Failure to satisfy any individual component will be classified as failure to achieve TO. Secondary Objectives Secondary objectives include: evaluation of the individual frequency of each TO component; identification of patient-, disease-, treatment-, and hospital-related factors independently associated with TO failure; assessment of variability in TO achievement among participating institutions; evaluation of the relative contribution of each TO component to overall TO failure; assessment of short-term postoperative outcomes associated with TO achievement; evaluation of long-term oncological outcomes, including overall survival and disease-free survival, during longitudinal follow-up; exploration of the role of TO as a standardized quality indicator for benchmarking colorectal cancer surgery across Italian surgical centers. Study Design ATOCCS is designed as a retrospective observational cohort study based on routinely collected clinical data. Eligible patients will be identified through institutional surgical databases, electronic medical records, operative registries, pathology reports, and hospital administrative databases. Consecutive patients meeting the eligibility criteria during the study period will be included in order to minimize selection bias and maximize external validity. No diagnostic or therapeutic interventions will be performed specifically for research purposes. Patient management, perioperative care, surgical strategy, and postoperative follow-up will remain entirely at the discretion of the treating multidisciplinary teams according to local institutional protocols and contemporary international guidelines. Because of its observational design, the study is intended to describe real-world surgical practice rather than evaluate the efficacy of a specific intervention. Participating Centers The study includes multiple Italian surgical units with established expertise in colorectal cancer surgery, coordinated within the ACOI collaborative research network. Participating centers include academic hospitals, tertiary referral institutions, and high-volume general hospitals distributed throughout Italy, thereby reflecting contemporary national clinical practice. Each participating institution designates a Local Principal Investigator responsible for: patient identification; verification of eligibility criteria; data extraction from institutional records; data entry into the electronic study database; resolution of data queries; compliance with study procedures and ethical requirements. Central study coordination oversees protocol implementation, data harmonization, quality assurance, and statistical analysis. Study Timeline Patients undergoing curative colorectal cancer surgery between 1 January 2022 and 31 December 2024 are eligible for inclusion. Clinical data are collected retrospectively after completion of routine clinical care. Following database completion and quality verification, statistical analyses will be performed according to a prespecified Statistical Analysis Plan. Longitudinal oncological follow-up will continue for up to five years after surgery to evaluate long-term survival outcomes in future analyses. Study Population, Eligibility Criteria, Study Procedures and Data Collection Study Population The study population consists of consecutive adult patients undergoing curative-intent colorectal cancer resection at participating Italian surgical centers during the predefined study period. Consecutive patient inclusion has been selected to minimize selection bias and to ensure that the study accurately reflects routine clinical practice across different institutional settings. The multicenter design allows inclusion of patients treated in academic hospitals, tertiary referral centers, and general hospitals, thereby increasing the external validity and generalizability of the study findings. Only patients undergoing surgical treatment with curative intent for histologically confirmed primary colorectal adenocarcinoma will be considered eligible for inclusion. Eligibility Criteria Inclusion Criteria Patients will be eligible if all of the following criteria are met: age ≥18 years; histologically confirmed primary colorectal adenocarcinoma; clinical stage M0 according to the TNM classification at the time of surgery; elective or emergency curative-intent colorectal resection; availability of complete perioperative and pathological data sufficient for assessment of Textbook Outcome components. Exclusion Criteria Patients meeting one or more of the following criteria will be excluded: metastatic disease (M1) identified preoperatively, intraoperatively, or on final pathological staging; palliative surgical procedures without curative intent; previous colorectal resection for colorectal cancer; local excision without formal oncological resection; recurrent colorectal cancer; missing essential information preventing assessment of the primary endpoint. Study Procedures Because of the retrospective observational design, no study-specific diagnostic tests, interventions, or modifications of clinical management will be performed. Each participating center will retrospectively identify eligible patients through institutional electronic medical records, operative registries, pathology databases, and hospital administrative systems. After confirmation of eligibility, trained investigators will extract predefined variables using standardized Case Report Forms (CRFs). The study follows a predefined workflow consisting of: identification of eligible patients; eligibility verification; extraction of demographic, clinical, operative, pathological, and postoperative variables; pseudonymization of patient data; electronic data entry into the central REDCap platform; automated and manual quality control procedures; resolution of data queries; database lock; statistical analysis according to the prespecified Statistical Analysis Plan. No patient contact is required during any phase of the study. Variables Collected To comprehensively characterize the study population and identify determinants of Textbook Outcome achievement, standardized variables will be collected across multiple domains. Patient Characteristics age; sex; body mass index; American Society of Anesthesiologists (ASA) physical status; smoking status; relevant comorbidities; previous abdominal surgery; performance status where available. Tumor Characteristics anatomical location; clinical TNM stage; pathological TNM stage; tumor size; histological subtype; tumor differentiation; lymphovascular invasion; perineural invasion; surgical margins; number of lymph nodes retrieved; number of metastatic lymph nodes. Treatment Variables urgency of surgery; surgical approach (open, laparoscopic, robotic); type of colorectal resection; multivisceral resection; creation of diverting stoma; conversion to open surgery; operative time; estimated blood loss; intraoperative complications; neoadjuvant treatment; adjuvant treatment when available. Postoperative Variables postoperative complications; Clavien-Dindo classification; Comprehensive Complication Index (when available); reintervention; intensive care admission; hospital length of stay; unplanned readmission; postoperative mortality; pathological quality indicators. Definition of Textbook Outcome Textbook Outcome represents the achievement of an optimal perioperative course and will be evaluated for every included patient. A patient will be considered to have achieved TO only when all predefined quality indicators are simultaneously fulfilled. The six mandatory components include: survival within 30 days after surgery; R0 resection with examination of at least 12 lymph nodes; absence of major postoperative complications (Clavien-Dindo grade III or higher); absence of unplanned reintervention; absence of unplanned stoma; postoperative hospital stay of ≤14 days without unplanned readmission. Failure of any individual component automatically results in classification as TO not achieved. Each component will also be analyzed separately to determine its individual contribution to overall TO failure. Data Collection and Database Management All study data will be entered into a secure web-based REDCap (Research Electronic Data Capture) database specifically developed for the ATOCCS study. The database incorporates standardized electronic Case Report Forms with predefined variable definitions, mandatory fields, range checks, logical consistency controls, and automated validation rules to maximize data completeness and accuracy. Each participating center will receive secure password-protected access limited to its own institutional dataset. Patient identifiers will never be uploaded to the central database. Before data entry, each patient will be assigned a unique study identification code, ensuring complete pseudonymization in accordance with the General Data Protection Regulation (GDPR). Central data management will include: automated data validation; consistency checks; missing data identification; query generation; investigator query resolution; periodic database audits; final database locking before statistical analysis. Any modifications to the database after initial entry will be fully traceable through electronic audit trails documenting the user, date, time, and nature of each change. To ensure data quality across participating centers, investigators will receive standardized instructions regarding variable definitions, data extraction procedures, and outcome assessment before data collection begins. Outcomes and Statistical Analysis Study Outcomes Primary Outcome The primary outcome of the study is the proportion of patients achieving Textbook Outcome (TO) following curative-intent colorectal cancer surgery. TO is considered achieved only when all predefined quality criteria are simultaneously fulfilled, reflecting an optimal perioperative course. Failure to satisfy any single component results in classification as failure to achieve TO. Secondary Outcomes Secondary outcomes include: frequency of achievement of each individual TO component; incidence of postoperative complications; incidence of major postoperative complications (Clavien-Dindo grade III or higher); 30-day postoperative mortality; unplanned reintervention; unplanned stoma formation; postoperative length of hospital stay; unplanned hospital readmission; oncological quality of resection (R0 status and lymph node yield); overall survival; disease-free survival; identification of independent predictors of TO failure; between-center variability in TO achievement; evaluation of TO as a quality indicator for benchmarking colorectal cancer surgery. Statistical Analysis A detailed Statistical Analysis Plan (SAP) will be finalized before database lock and prior to any inferential analyses. All analyses will be conducted using validated statistical software. Statistical significance will be defined as a two-sided P value \<0.05. Continuous variables will first be assessed for distributional assumptions using graphical methods and appropriate normality tests. Normally distributed variables will be reported as means with standard deviations and compared using Student's t-test or analysis of variance (ANOVA), as appropriate. Non-normally distributed variables will be summarized as medians with interquartile ranges (IQRs) and compared using the Mann-Whitney U test or Kruskal-Wallis test. Categorical variables will be presented as absolute frequencies and percentages and compared using Pearson's χ² test or Fisher's exact test when appropriate. Primary Analysis The primary analysis will estimate the overall proportion of patients achieving TO within the study cohort. Exact confidence intervals will be calculated for TO rates. Each individual TO component will also be analyzed separately to quantify its contribution to overall TO failure. Multivariable Analysis Independent predictors of TO failure will be identified using multivariable logistic regression. Selection of covariates will be based on: biological plausibility; previous literature; clinical relevance; potential confounding effects. Variables considered for adjustment may include: age; sex; body mass index; ASA physical status; relevant comorbidities; tumor location; pathological stage; surgical approach; urgency of surgery; multivisceral resection; neoadjuvant therapy; participating center. Adjusted odds ratios (ORs) will be reported together with 95% confidence intervals. Model discrimination and calibration will be evaluated using appropriate statistical methods. Survival Analysis Overall survival and disease-free survival will be estimated using the Kaplan-Meier method. Comparisons between patients achieving and not achieving TO will be performed using the log-rank test. Independent prognostic factors associated with long-term outcomes will be evaluated using multivariable Cox proportional hazards regression after verification of proportional hazards assumptions. Hazard ratios (HRs) with corresponding 95% confidence intervals will be reported. Missing Data Data completeness will be assessed before statistical analysis. Patterns of missing data will be explored to determine whether observations are missing completely at random, missing at random, or not missing at random. When appropriate, multiple imputation techniques may be considered for variables with incomplete data, provided that assumptions for imputation are met. Sensitivity analyses based on complete-case datasets may also be performed to evaluate the robustness of the findings. Variables with excessive missingness or poor data quality will not be included in multivariable modelling. Subgroup Analyses Predefined subgroup analyses may include comparisons according to: colon versus rectal cancer; open versus minimally invasive surgery; laparoscopic versus robotic surgery; elective versus emergency procedures; age categories; ASA classification; pathological stage. These analyses are considered exploratory and will be interpreted cautiously. Between-Center Variability Institutional variation in TO achievement will be explored by comparing adjusted TO rates across participating centers. When appropriate, risk-adjusted analyses will be performed to account for differences in patient case-mix and baseline characteristics. These analyses are intended to evaluate variability in surgical performance and to identify potential opportunities for quality improvement rather than to rank individual institutions. Sensitivity Analyses Sensitivity analyses may be conducted to evaluate the robustness of the primary findings. Potential analyses include: complete-case analysis; exclusion of emergency procedures; exclusion of patients with missing pathological variables; alternative definitions of postoperative morbidity where clinically justified. Sample Size Considerations The planned sample size largely exceeds the minimum number required to provide adequate statistical precision for estimation of TO rates and multivariable modelling. Given the anticipated nationwide recruitment across participating centers, the study is expected to include several thousand patients, thereby providing substantial statistical power for the primary analyses and enabling robust evaluation of clinically relevant subgroups. Consequently, the study is powered not only to estimate TO incidence with high precision but also to investigate independent determinants of TO failure and between-center variability with adequate statistical reliability. Ethical Considerations, Data Governance, Quality Assurance and Dissemination Ethical Considerations The study will be conducted in accordance with the principles of the Declaration of Helsinki, applicable national legislation, the European General Data Protection Regulation, and relevant institutional policies governing retrospective observational research. The ATOCCS study received a favorable opinion from the competent National Ethics Committee for Public Research Bodies and National Institutions, documented under reference AOO-ISS No. 0047829 of 20 November 2025. Each participating center will comply with local institutional requirements before initiating data collection. Where required, participating institutions may formally adopt the national ethical opinion or obtain additional local authorization in accordance with their internal procedures. Because the study is retrospective, observational, and based exclusively on data generated during routine clinical care, no additional diagnostic or therapeutic procedures will be performed for research purposes. The requirement for individual informed consent may be waived where permitted by the competent ethics committee and applicable legislation. The study does not alter patient management, surgical strategy, perioperative care, pathological assessment, postoperative surveillance, or oncological treatment. Confidentiality and Data Protection All study data will be handled in accordance with the European General Data Protection Regulation and applicable Italian data-protection legislation. Before entry into the central study database, each patient will be assigned a unique study identification code. Direct personal identifiers, including names, dates of birth, medical record numbers, addresses, telephone numbers, and fiscal identification data, will not be entered into the central database. The correspondence between the study identification code and the patient's identity will be maintained exclusively at the participating center in a secure local re-identification log accessible only to authorized study personnel. The coordinating center and the statistical analysis team will receive only pseudonymized data and will not have access to information that directly identifies individual participants. Data access will be role-based and restricted to authorized investigators according to their responsibilities within the study. Electronic Data Capture and Data Governance Study data will be collected through a dedicated REDCap electronic data-capture platform. The platform is hosted within the institutional infrastructure of Azienda Ospedaliero-Universitaria Careggi, Florence, which is responsible for the secure technical management and storage of the pseudonymized study database in accordance with applicable data-protection and institutional-security requirements. Each participating center will be granted password-protected access to its own records. Access permissions will be assigned according to predefined user roles, and investigators will not ordinarily be able to access records entered by other participating institutions. The electronic database will include: predefined variable formats; controlled response fields; mandatory fields for essential variables; permissible value ranges; logical consistency checks; automated validation rules; date and chronology checks; audit trails recording data entry and modification. The final analytical dataset will be generated only after completion of data validation, resolution of outstanding queries, and formal database lock. Data Quality Assurance Data quality will be supported through standardized study procedures applied across all participating centers. Before data collection, investigators will receive: the approved study protocol; standardized variable definitions; instructions for patient identification and eligibility assessment; guidance for classification of postoperative complications; definitions of all Textbook Outcome components; instructions for REDCap data entry; procedures for responding to data queries. Central quality-control procedures will include automated validation, manual consistency review, completeness assessment, duplicate-record detection, and verification of clinically implausible or internally inconsistent values. Queries will be issued to local investigators whenever clarification, correction, or source-data verification is required. Data changes will remain traceable through the REDCap audit trail. The coordinating team may request targeted verification of selected variables when inconsistencies, unusual distributions, or center-specific data patterns are identified. Data-quality procedures are intended to improve completeness and reliability without altering the observational nature of the study. Management of Protocol Deviations Any relevant deviation from the approved protocol, including changes in eligibility criteria, outcome definitions, data-collection procedures, or statistical methods, will be documented by the coordinating investigators. Substantial protocol amendments will be submitted to the competent ethics committee and participating institutions when required. Analytical deviations from the prespecified Statistical Analysis Plan will be transparently reported and justified in resulting scientific publications. Study Governance The study is coordinated through the ATOCCS collaborative network on behalf of the Italian Association of Hospital Surgeons. The central coordinating group is responsible for: overall study oversight; protocol implementation; communication with participating centers; maintenance of standardized definitions; database development and supervision; data-quality monitoring; statistical-analysis coordination; interpretation of study findings; preparation of scientific reports and manuscripts. Each participating center appoints a local principal investigator responsible for local regulatory compliance, accurate patient identification, data extraction, data entry, source-data verification, and timely resolution of queries. Authorship and collaborative recognition will be assigned according to predefined study policies and internationally accepted authorship criteria. Risk to Participants Participation in the study does not expose patients to additional procedural, pharmacological, radiation-related, or clinical risk. The principal foreseeable risk is related to confidentiality and unauthorized disclosure of personal health information. This risk is minimized through local pseudonymization, restricted access, secure electronic storage, role-based permissions, and exclusion of direct personal identifiers from the central database. No results from the study database will be used to modify the treatment of individual participants. Dissemination of Results Study findings will be disseminated through peer-reviewed scientific publications, presentations at national and international conferences, professional educational activities, and reports prepared within the ATOCCS and ACOI collaborative networks. Results will be reported at aggregate level. Individual patients will not be identifiable in any publication, presentation, or public report. Center-level analyses will primarily be used to investigate variation in care and identify opportunities for quality improvement. Public reporting of identifiable institutional performance is not planned unless separately authorized and methodologically justified. The results are expected to contribute to: validation of Textbook Outcome in real-world colorectal cancer surgery; development of risk-adjusted quality benchmarks; identification of potentially modifiable determinants of TO failure; improvement of perioperative pathways; standardization of quality assessment across surgical centers; planning of future prospective and interventional studies. Both positive and negative findings will be considered for dissemination in order to reduce selective reporting and provide a complete assessment of the study objectives. Data Sharing De-identified or pseudonymized study data may be made available for scientifically valid secondary analyses following submission of a formal research proposal, approval by the study coordinating group, verification of ethical and data-protection requirements, and execution of an appropriate data-sharing agreement. Data sharing will not include direct personal identifiers or local re-identification files. The availability and extent of data sharing will depend on applicable legislation, ethics approvals, institutional agreements, and the governance policies of the ATOCCS collaborative network.