This is an observational multicentre retrospective and prospective cohort study, and a
qualitative study. The project will have three working packages:
Work package 1 - maintenance of a colorectal surgery database
Work package 2 - prospective collaborative national UK study
Work package 3 - qualitative analysis with semi-structured interviews
WORK PACKAGE 1 - COLORECTAL SURGERY DATABASE:
Data collected includes:
Basic demographic information
Co-morbidities at time of surgery
Other cancer treatments
Final cancer staging and diagnosis
Type of procedure
Methods of reconstruction
Use of healthcare resource: (theatre time, surgical teams, use of consumables, index
operation intensive care stay, total length of stay, planned or emergency
readmissions, use of imaging for complications, re-interventions, and outpatient
clinic use).
Morbidity - empty pelvis syndrome complications with collation of all complications
that occurred summarised into: (the highest Clavien-Dindo (CD) score, and the
comprehensive complication index by accumulating CD graded complications that a
patient has as a result of their surgery.
Survival: overall and disease-free survival
Patient reported outcome measures
Any other routinely collected clinical data will be included. Of particular mention we
will include and analyse Cardiopulmonary exercise testing data, data derived from the
perioperative medicine screening and assessment, data derived from prehabilitation,
radiomic data e.g. muscle/fat structure and function derived from CT, MRI or PET-CT.
WORK PACKAGE 2 - PROSPECTIVE COLLABORATIVE STUDY:
Abdominoperineal excision and pelvic exenteration can be used in a wide range of cancer
types, and in the case of pelvic exenteration can be used to manage both recurrent and
primary cancers. The principal PROM used will be the EORTC QLQ-C30 with its modular
questionnaires giving additional insight into disease-specific quality of life.
All amendments have been made in line with NIHR RfPB funding received in November 2024.
Patients will be recruited once a decision to undertake abdominoperineal excision or
pelvic exenteration surgery has taken place. Participants will be sent a participant
information sheet which will include the dates of when participants can expect follow up
telephone calls, with information on how to contact the study team to change these should
participants wish to. Once consented participants will undergo the following PROMs as
part of their baseline questionnaire:
EORTC QLQ-C30 with specific cancer-type modules
EQ-5D-5L
LRRC QoL
Decision Regret
Comprehensive Score for Financial Toxicity (COST), financial status questionnaire
(non-validated) and Patient employment status questionnaires.
The investigators anticipate that participants will be able to self-assess the above
PROMs on a paper printed form, however a member of the research team will be available to
support the participant if required.
Clinical information will also be collected pre-operatively, including: demographic
information, co-morbidities, cancer staging, and previous cancer treatments. Patients
will be given copies of the follow up questionnaires at this time so participants have
them as a reference when completing follow up questionnaires. Patients can opt for either
email or telephone follow up for quality of life, if opting for email REDCap study will
automatically send out emails based on the date of surgery.
The patient will then undergo their surgery with method of reconstruction at the
discretion of the operating surgeon(s).
Following the index admission researchers will enter details on the hospital stay:
Type of procedure
Methods of reconstruction
Theatre time
Theatre teams
Use of consumables
Length of intensive care and hospital stay
Use of imaging for complications
Re-interventions for complications
Discharge destination following index admission
Final cancer staging and other pathological outcomes.
Perineal and empty pelvis morbidity, and overall Clavien-Dindo and Comprehensive
Complication Index
NHS healthcare utilisation costs
If applicable survival and cause of death
At 3 months post-operatively questionnaires will be repeated over the telephone
including:
EORTC QLQ-C30 with cancer-specific module
EQ-5D-5L
LRRC QoL
Decision Regret
Comprehensive Score for Financial Toxicity (COST), Patient reported heath resource
utilisation and NHS healthcare utilisation costs.
At this same time point researchers will review routinely collected clinical data and use
of in-hospital health resources to include:
In-hospital health resource use: planned or emergency re-admissions, use of imaging
to investigate complications, re-interventions (surgical and radiological), planned
or unplanned outpatient visits.
Longitudinal CCI scores updated, and if applicable an increase in CD if a more
severe complication develops.
If applicable cancer recurrence, survival and cause of death will be recorded.
Patients will be emailed or telephoned on the date specified on their participant
information sheet, however if this time is not convenient then a better time will be
arranged with the patient. If participants do not respond to the email or first telephone
call then the investigators will make a further three separate attempts to contact the
patient. If there is still no response participants will be deemed lost to the study.
This follow up process will be repeated again at 6 months and 12 months. At the 12 month
time point the investigators will ask patients additional questions on their use of
health care resources and their current financial status, to include:
Use of community health resource use due to complications including: GP appointments
and nursing home care days required for recovery from surgery.
Use of healthcare resources at hospitals other than the treating hospital - clinic
appointments and admissions
At the end of this time the patient will have completed the study.
WORK PACKAGE 3 - QUALITATIVE STUDY:
The qualitative study will recruit patients from work packages 1 and 2. The investigators
will invite 30 purposefully sampled patients that are 3 months following their surgery.
Suitable patients will be contacted with a posted participant information sheet and a
telephone follow up call to allow participants to ask questions about the study.
Following informed consent semi-structured interviews will take place with
semi-structured open questions to guide the discussions.
Interviews will be recorded on an encrypted audiorecorder and then transcribed. The
investigators will initially undertake three pilot interviews to review that the
semi-structured interview schedule is adequate to fully explore our objectives and to
obtain good quality interview transcripts for analysis. These pilot interviews once
completed will be reviewed by the research team. The semi-structured interview schedule
questions may be changed if the interviews are of poor quality, pilot interviews
demonstrate new insights from participants that suggest fruitful lines of enquiry, or
inconsistencies that require further exploration. If subsequent interviews are very
different than the pilot interviews following these changes, then these early interviews
will not be included in the qualitative analysis and additional patients will be
recruited.
Patients recruited at 3-months following surgery will be offered a repeat interview at
12-months following their surgery
DATA ANALYSIS PLAN:
Statistical analysis:
The investigators will be collecting data on the timepoints as described above.
Continuous data will be will be summarised using descriptive statistics (mean, median,
standard deviation, lower and upper quartiles). Categorical data will be summarised using
counts and percentages.
As studies are non-randomised, the investigators will utilise regression models and
principal component analysis to adjust for confounding in this observational study.
In order to obtain our outcomes a brief summary of analyses is below.
Work package 1 (Colorectal Database):
Primary analysis:
- Frequency of morbidity relating to the empty pelvis syndrome and perineal wound will
be compared for different types of perineal reconstruction will be analysed using
multiple linear regression.
Secondary analysis:
Overall morbidity will be obtained using highest CD scores for different methods of
perineal reconstruction analysed using multiple linear regression.
Disease free and overall survival will be analysed using Kaplan-Meier curves and log
rank tests with a multivariate Cox regression hazard model to identify factors
independently associated with survival, including method of reconstruction.
Exploratory analysis:
Other factors including age, gender, BMI, final staging, co-morbidities, type of
operation, neoadjuvant chemoradiotherapy and use of intra-operative electron
radiotherapy will be included in the analysis
Other outcomes including primary operation time, lengths of stay, and readmissions
will be explored
Work package 2 (prospective study):
Primary and secondary analysis:
Patient reported outcome measures will be analysed using regression models,
including linear mixed-effects models for repeat measures and adjusted analyses.
The same clinical data fields will be collected as per work package 1, the analysis
above repeated with exploratory analysis to find factors that are independently
significantly associated with changes in the PROMs.
Health economic analysis:
Work package 1 (retrospective study):
The investigators will collect data on use of hospital healthcare resources in each
patient group. The investigators will collect resource use for each parameter required
for each patient. The investigators will then undertake costing using a micro-costing
approach and health resource group costing for each parameter. Applying costs to each
parameter will use a combination of manufacturer prices for consumables, National Cost
Collection for the NHS, National Schedule of NHS Costs, NHS National Tariff and the Unit
Costs of Health and Social Care from the Personal Social Services Research Unit. The
investigators will then report overall costs associated with different methods of
perineal reconstruction and the cost of complications that were encountered.
Work package 2 (prospective study):
The investigators will collect hospital healthcare resource use data prospectively and
apply micro-costing to these parameters in the same way as per work package 1 for each
patient and their method of reconstruction. The investigators will also ask patients to
provide us with use of community healthcare resources as a result of their surgery, data
for which the investigators will not be able to obtain from their clinical notes.
Participants will receive EQ-5D-5L and EORTC QLQ-C30 questionnaires at baseline, 3
months, 6 months and 12 months. From these responses the investigators will map onto
EQ-5D-3L in order to reduce the overall number of questionnaires patients are undertaking
in our study. This will allow us to plot EQ-5D-3L responses for different methods of
reconstruction and plot the area under the curve. Within the trial time a health economic
model would be built which would follow the NICE reference case and ISPOR Task Force
guidelines on health economic analysis. This will enable us to present Quality Adjusted
Life Years and incremental cost-effective ratios for the different methods of perineal
reconstruction.
Qualitative analysis:
Audio transcription will be transcribed verbatim, checked against the recording and
anonymised. Data will be uploaded to NVivo for data management.
Preliminary summaries will be written after each interview to identify emerging themes to
follow-up discussions. The follow-up interview will ask patients to reflect on the
content of their previous interview and discuss any changes.
Longitudinal interview analyses will use constant comparative methods from grounded
theory and data coded using NVivo's framework matrix facility to examine themes
longitudinally, enabling comparisons within each case and across cases, focusing on
changes over time. The stages of data analysis, drawing on longitudinal comparisons, will
include:
Initial reading: Review interview data.
Preliminary coding: Two researchers code the data.
Team meeting: Discuss and refine codes with wider research/PPI team.
Individual Case Coding: Code all interview data for each participant.
Categorising Codes: Group codes into categories for each case.
Longitudinal comparisons: Within case and category comparisons focussing on changes
over time.
Focused coding: Examine categories in relation to emerging concepts and phases.
Discussion on Themes: PPI co-led focus group discussions of final themes.
Development and Dissemination: Report write up are dissemination.
Based on an iterative process, emerging themes will be used to develop explanatory
accounts. Analysis will draw on sociological perspectives of illness adaptation, recovery
and self-management in addition to psychological theories of individual behaviour change.
All qualitative and quantitative data will inform 3 patient focus groups, where PPI and
charity collaborators along with 5 newly trained PPI members will discuss data analyses
from a patient perspective, contributing to initial discussions around developing a
patient decision aid.