Subjects of study (inclusion criteria): All patients over 18 years of age who will be
operated on a scheduled basis for colorectal cancer within an intensified recovery program
(PRI) and who do not present any exclusion criteria.
Exclusion Criteria: - Urgent surgery; -Existence of other concomitant surgical processes;
-Patients diagnosed in stage IV cancer; -Patients who refuse to participate.
Participating hospitals: Selected for their interest in intensified recovery and for having
established a multidisciplinary team with the program (PRI) for colorectal surgery
recommended by the Spanish Ministry of Health. Each center will select from the
multidisciplinary team the researchers who will be part of this project as collaborators,
ideally the facilitators of the PRI program in that center.
Variables: Patients will be recruited by local researchers from the Anesthesiology and
Resuscitation and/or General Surgery services of each participating center before performing
the surgical intervention. Informed consent will be requested from all subjects who
voluntarily participate in the study.
Compliance: As we have commented before and according to the literature, we will define
a hospital with an intensified recovery program (PRI) that has a consensus protocol,
based on evidence, multidisciplinary, with the support of the center (management) and
that has fulfilled more than 70% of the protocol (annex 1) according to the process
indicators. The rest of the hospitals will be considered a non-PRI hospital.
Demography: Age, sex, BMI, smoking and fitness level of the American Society of
Anesthesiologists (ASA). BMI in the surgical indication. Blood transfusion.
Comorbidities: Presence of hypertension, diabetes mellitus, coronary artery disease,
heart failure, cirrhosis, stroke or transient ischemic attack, COPD / Asthma, atrial
fibrillation, heart failure, OSAS. Anemia
Related to Surgery and Treatment: Date IQ. Surgical procedure, approach, duration of
surgery, estimated bleeding. Curative surgery (R0) or non-R0 (R1-R2). Adjuvant
chemotherapy Adjuvant radiotherapy Perioperative transfusion.
Variables related to staging: Tumor typology. Growth pattern. Degree of differentiation.
Presence of Vascular / lymphatic / perineural invasion / Satellites. Margin affectation.
Seal ring cells. K-ras. T tumor piece. No tumor piece. Tumor m. Tumor stage according to
AJCC classification.
Related to the follow-up:
In-hospital complications at 60 days of follow-up that will be recorded are: surgical
complications, infectious complications, cardiovascular complications and other types of
complications. Each complication will be classified as mild, moderate or severe. The
Clavien-Dindo classification will also be used. Perioperative mortality: The number and
percentage of deaths within 60 days of surgery. Hospital Stay: hospital stay is defined as
the duration in days from the date of admission to hospital discharge. Quality of life
according to the EuroQol Five questionnaire. (EQ-5D).
Overall mortality: The number and percentage of deaths occurred since the intervention until
the end of the follow-up period. Overall survival: patients alive from surgery to the last
control. Disease-free survival: number of patients alive and without cancer recurrence from
the intervention period until the end of follow-up.
Disease recurrence: detected by CT or FCC, from the day of the intervention until the end of
the follow-up.
Patient Follow-up Plan: 5 years after surgery. Data collection: The data will be collected in
individual hospitals on a paper CRD for each patient recruited. This will include patient
identification data in order to allow monitoring of clinical results. The data will be
encoded by generating a unique numerical code and transcribed by local researchers in a
database using an electronic CRD (eCRD). The data collection platform used will be Castor EDC
https://www.castoredc.com/. Castor EDC complies with all applicable laws and regulations:
good clinical practice (GCP), 21 CFR Part 11, EU Annex 11 and the European Data Protection
Directive. Each patient will only be identified in the electronic CRD by their numerical
code. In each center a list of patients will be used to match the identification codes of the
individual patients' database in order to record the clinical results and provide any of the
missing data. All identifiable data collected, processed and stored for the purposes of the
project will be kept confidential at all times and will comply with the guidelines of Good
Clinical Practice for Research (GCP) and the General Data Protection Regulation (GDPR)
(Regulation (EU) ) 2016/679).
Data analysis: Sample size: understanding, according to the literature, that only 60% of the
centers with a PRI achieve more than 70% of compliance, we consider the scenario of 6 PRI and
4 non-PRI centers adequate among the 10 who collaborate in this research project. Estimating
a difference in overall survival between centers around 10% (65% vs. 75%), with a power of
80%, a 95% confidence and 5% of possible losses, a minimum sample size of 366 is estimated
patients in each group (732 patients in total). For the study of survival, only patients with
a minimum follow-up of two years (first 12 months of the study) will be considered. However,
they will continue to be recruited until the end of the three years for the study of
secondary objectives.
Understanding that the main objective, study of survival, may be subject to inherent aspects
of each center, independent of the intervention, it is necessary to create comparable
treatment and control groups for which the Propensity Score (Propensity Score Matching)
method will be used. A descriptive analysis of the data will be carried out: Qualitative
variables will be presented by frequency distribution of the percentages of each category.
The quantitative variables studied will be explored with the Kolmogorov - Smirnov conformity
test. Bivariate Analysis Comparison between variables (factors): The association between the
factors will be investigated by hypothesis contrast tests, with comparison of proportions
when both variables are qualitative (chi square, Fisher's exact test), mean comparisons when
one of them is quantitative (Student's t, ANOVA, and if they do not follow the normal
distribution, the Mann-Whitney U test or the Kruskall-Wallis test) and bivariate correlations
(Coef. Pearson Correlation) when both are quantitative or, if the conditions are not met of
application, the Spearman correlation. For comparisons in related samples when one of them is
quantitative, Student's t-test and/or ANOVA will be used for repeated measurements and
Wilcoxon or Friedman's test when do not follow normal distribution). Multivariate analysis:
To study the relationship of each variable controlling the possible effect caused by third
variables. The analysis will be completed using multivariate regression models. Survival
analyzes will be performed using the Kaplan-Meier method for survival comparisons the
log-rank test will be used. The effects will be considered significant if p <0.05.
Monitoring and audit: The data collection documents will be audited to ensure that study
activities are carried out in accordance with the protocol, good clinical practice and
applicable regulatory requirements. In the participating hospitals, local study documents can
be selected for local auditing. The quality of the data will be audited.
Limitations of the study: Those of a prospective non-randomized study. Difficulty in
recruiting patients for potential structural or multidisciplinary team problems.
Inappropriate number of patients in any of the arms due to a very high or very low level of
compliance.
