Clinical trial NCT04893876: The OPERa Study: Evaluating QoL After Rectal Cancer Surgery
Official title: The OPERa Study: A Multicenter Observational Prospective Cohort Study to Evaluate Determinants of Long-Term Quality of Life Following Restorative Proctectomy for Rectal Cancer Treatment
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Rectal Cancer
Quality of Life
Bowel Dysfunction
Sexual Dysfunction
Urinary Dysfunction
Emotional Distress
Surgery
Lead sponsor: Jewish General Hospital
Sponsor class: OTHER
First posted: 2021-05-20
Enrollment: 1200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All consecutive patients \>18 years with histopathologically confirmed primary rectal cancer ≤15cm from the anal verge who are planned for curative treatment.

Brief summary: Advances in rectal cancer management have significantly reduced morbidity and mortality. The most commonly performed operation for rectal cancer is restorative proctectomy (RP), leaving up to 70% with long-term bowel dysfunction called Low Anterior Resection Syndrome (LARS). LARS manifests as stool frequency, incontinence and difficult defecation. LARS, along with other functional impairments such as sexual and urinary dysfunction (SUD), can impact quality of life (QoL) and cause emotional distress. High-quality longitudinal data on these sequalae are lacking, leading to variable estimates of their prevalence, risk factors and prognosis. Most studies are European, cross-sectional, lack pre-treatment evaluation and long-term follow-up, and use inconsistent assessment measures. Thus, a North American study that evaluates patients longitudinally from diagnosis will provide quality data to fill this knowledge gap.

The main aim of the proposed study is to contribute evidence regarding the impact of LARS, SUD, emotional/financial distress, and patient activation on long-term post-treatment QoL in North American rectal cancer after RP.

This multicenter North American, observational, prospective cohort study relies on validated patient reported outcome measures (PROMs) at diagnosis, during and post-treatment. Patients from 20 sites will be recruited over 2 years and followed for 3 years. The primary endpoint is QoL as measured by the European Organization for Research \& Treatment of Cancer QoL questionnaire. We anticipate accrual of 1200 patients. Factors associated with QoL will be explored. Impact of patient activation in relation to functional outcomes on QoL over time will be explored using a difference-in-differences approach. The study involves a multidisciplinary team who will provide expertise in research methodology, nursing, oncology and surgery.

The main contributions of this study are 1) provision of reference baseline North American values for important rectal cancer PROMs for clinical and research use, 2) an understanding of the evolution of functional outcomes and QoL post-treatment to counsel patients peri-operatively and throughout survivorship, and 3) to provide the basis for future tailored programs to support rectal cancer survivors.

Detailed description: Advances in rectal cancer management have significantly reduced morbidity and mortality. The most commonly performed operation for rectal cancer is restorative proctectomy (RP), leaving up to 70% with long-term bowel dysfunction called Low Anterior Resection Syndrome (LARS). LARS manifests as stool frequency, incontinence and difficult defecation. LARS, along with other functional impairments such as sexual and urinary dysfunction (SUD), can impact quality of life (QoL) and cause emotional distress. There is no well-established treatment strategy for LARS or SUD. High-quality longitudinal data on these sequalae are lacking, leading to variable estimates of their prevalence, risk factors and prognosis. Most studies are European, cross-sectional, lack pre-treatment evaluation and long-term follow-up, and use inconsistent assessment measures. Thus, a North American study that evaluates patients longitudinally from diagnosis will provide quality data to fill this knowledge gap.

The main aim of the proposed study is to contribute evidence regarding the impact of LARS, SUD, emotional/financial distress, and patient activation on long-term post-treatment QoL in North American rectal cancer after RP. This study aims to address the following research questions: 1): How do North American rectal cancer patients who underwent RP experience changes in function (bowel, sexual and urinary), distress (emotional and financial) and QoL after RP from baseline through early and late timepoints following treatment? 2): How do patient-, disease-, treatment-, functional- and distress-related factors predict QoL at baseline and at early and late timepoints post-treatment?

This multicenter North American, observational, prospective cohort study relies on validated patient reported outcome measures (PROMs) at diagnosis, during and post-treatment. Patients from 20 sites will be recruited over 2 years and followed for 3 years. The primary endpoint is QoL as measured by the European Organization for Research \& Treatment of Cancer QoL questionnaire. We anticipate accrual of 1200 patients. Estimating a 30% attrition rate, in 1000 different simulated datasets and α=0.05, we will be able to detect a 1 point difference in QoL 88% of the time (95%CI: 85.8, 90.0). Given that a 10-point difference is considered clinically significant, this sample size affords good precision. 1) QoL, LARS, SUD, emotional/financial distress will be measured at baseline, early (12 \& 18 months) and late (2 \& 3 years) timepoints. 2) Changes over time for each outcome will be studied using linear mixed models (LMM) and generalized LMM as appropriate to account for the hierarchical and longitudinal structure of the data. 3) Factors associated with QoL will be explored using LMM. 4) Impact of patient activation in relation to functional outcomes on QoL over time will be explored using a difference-in-differences approach. The study involves a multidisciplinary team who will provide expertise in research methodology, nursing, oncology and surgery.

The main contributions of this study are 1) provision of reference baseline North American values for important rectal cancer PROMs for clinical and research use, 2) an understanding of the evolution of functional outcomes and QoL post-treatment to counsel patients peri-operatively and throughout survivorship, and 3) to provide the basis for future tailored programs to support rectal cancer survivors.

Eligibility criteria: Inclusion Criteria:

* Patients \>18 years with histopathologically confirmed adenocarcinoma of the rectum, defined as tumor ≤15cm from the anal verge who are planned for RP ± neoadjuvant treatment or WW (CRT alone without surgery).

Exclusion Criteria:

* Metastatic disease at diagnosis;
* Planned for abdominoperineal resection (APR), low Hartmann's or pelvic exenteration (PE);
* Cannot be contacted by telephone;
* Unable to read and comprehend English or French;
* Unable to give clear and informed consent.

Primary outcomes:
measure: Global Quality of Life (QoL)
timeFrame: 3 years
Secondary outcomes:
measure: Low Anterior Resection Syndrome Score
timeFrame: 3 years
measure: Female Sexual Dysfunction
timeFrame: 3 years
measure: Male Sexual Dysfunction
timeFrame: 3 years
measure: Female Urinary Dysfunction
timeFrame: 3 years
measure: Male Urinary Dysfunction
timeFrame: 3 years
measure: Emotional Distress
timeFrame: 3 years
measure: Financial Strain
timeFrame: 3 years
measure: Patient Activation
timeFrame: 3 years
measure: Frailty
timeFrame: 3 years
Other outcomes:
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