Clinical trial NCT06788834: Multimodal Prehabilitation in Cancer Surgery
Official title: Multimodal Prehabilitation in Cancer Surgery PROPOSE Trial (PRehabilitation in Oncological Patients undergOing SurgEry): A Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cancer Surgery
Keywords: Prehabilitation
Functional recovery
Relaxation
Exercise
Diet
Nutrition
Functional walking
Hospital stay
Multimodal prehabilitation program
Standard treatment
Anesthesiology
Lead sponsor: Università Vita-Salute San Raffaele
Sponsor class: OTHER
Collaborators: name: Prof. Pasquale Sansone
name: Prof. Eugenio Garofalo
name: Prof. Tiziana Bove
name: Dr. Claudia Brusasco
name: Prof. Gabriele Baldini
name: Dr. Nicola Passuello
name: Dr. Monica Gualtierotti
name: Prof. Luca Carlo Nespoli
First posted: 2025-01-23
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The PROPOSE RCT is a two-arm randomized controlled trial that will be conducted to test the efficacy of a personalized, multidisciplinary pre-operative prehabilitation program (preventive prehabilitation) to reduce serious complications and facilitate recovery after surgery in high-risk patients.

The multimodal prehabilitation program is a preoperative intervention that includes exercise training, nutritional therapy and anxiety reduction techniques, with the aim of preventing or mitigating the functional decline brought about by surgery. 400 patients scheduled for elective major abdominal (including urological), thoracic (including breast) or gynecological cancer surgery will be enrolled. They will be randomized (1:1 ratio) and assigned either to the intervention group (Prehabilitation) or to the control group, which will only be treated according to the usual standard of care within the Enhanced Recovery After Surgery (ERAS) pathways.

Detailed description: The standard treatment for most solid cancer includes surgery and concurrent medical therapies, both of which have been shown to significantly improve prognosis. However, cancer treatments impose impactful physiological stress and have detrimental effects on acute and long-term health outcomes.

Physical, nutritional, and mental status can influence surgical outcomes, functional recovery and quality of life throughout the course of the disease.

The importance of postoperative rehabilitation on physical performance and recovery is well-recognized. However, the preoperative period provides a unique opportunity to address comorbidities and modifiable risk factors. In addition, the metabolic stress induced by neoadjuvant therapy has been documented to frequently result in muscle atrophy and diminished functional capacity. The recognition that selected risk factors of poor postoperative outcome can be modified has prompted clinicians to identify proactive interventions to facilitate the recovery process. In this context, prehabilitation, aimed at enhancing the patients' functional capacity to enable them to withstand the physiological stress of surgery, has emerged as a promising approach. Although the term prehabilitation is not novel, the concept of optimizing patients before acute stressor or treatment has gained attention over the last decade. Nonetheless, quantifiable evidence of its effectiveness has yet to be fully demonstrated.

This study is a multicenter randomized controlled trial to assess the efficacy of personalized procedure-specific prehabilitation programs on patient-centered surgical outcomes. A total of 400 patients will be recruited by systematic screening of patients scheduled for elective surgical procedures. All patients undergoing elective major abdominal (including urological), thoracic (including breast) or gynecological cancer surgery undergoing major cancer surgery will be screened for eligibility and those who meet the inclusion/exclusion criteria will be approached for consent. Research personnel will use a web-based randomization system to assign patients (1:1 ratio) to either the prehabilitation or control arm. Study personnel will also collect data on recruitment rates, with reasons for non-enrolment.

Eligible patients will be randomly assigned to 1 of 2 treatments:

1. multimodal prehabilitation program for at least three weeks started as soon as possible before surgery;
2. standard care.

The multimodal prehabilitation program will be individualized by carefully integrating and adapting various components to meet individual needs. The program will last at least three weeks (plus maintenance in case of delayed surgery), and will incorporate exercise training, nutritional therapy, and anxiety reduction techniques. After enrollment, patients will receive initial contact from trained personnel through telemedicine. To ensure personalized care, a comprehensive assessment will be conducted to identify specific physical, nutritional, or psychological challenges. Based on this assessment, a customized intervention plan will be prescribed to achieve tailored exercise training, optimized nutrition, and effective distress-coping strategies. All patients will be reassessed the day before surgery and 30 days after surgery. Based on the data obtained during the multimodal assessment, different domains and levels of care will be prescribed, focusing on exercise training, nutrition optimization, or distress-coping techniques-or a combination of these

Eligibility criteria: Inclusion Criteria:

* Adult patient (age \> 18 years);
* Scheduled for elective major abdominal (including urological), thoracic (including breast) or gynecological cancer surgery;
* Signed informed consent.

Exclusion Criteria:

A) Co-morbid medical, physical, and mental conditions interfering with the ability to complete study procedures, such as:

* Acute or unstable cardio-respiratory conditions (e.g., unstable angina or symptomatic severe aortic stenosis);
* Severe/end-stage organ diseases (e.g., cardiac failure NYHA functional classes III-IV, COPD FEV1 \<50% pred, end-stage kidney or liver disease);
* American Society of Anesthesiologists (ASA) physical status classes 4-5;
* Disabling orthopedic and neuromuscular disease;
* Psychosis, dementia;
* Symptomatic anemia with a hemoglobin value \< 7 gr/dl.

B) Patients with both optimal functional capacity (a Duke activity status index \[DASI\] score \> 45) and optimal nutritional status (NRS-nutrition screening tool-score \< 2).

Primary outcomes:
measure: Assess the impact of prehabilitation on severe postoperative complications among high-risk patients undergoing oncological surgery
timeFrame: 30 days after surgery
Secondary outcomes:
measure: Time to Functional Recovery (TFR)
timeFrame: 30 days after surgery
measure: Lenght of hospital stay (LOS)
timeFrame: 30 days after surgery
measure: Days at home up to 30 days after surgery (DAH-30)
timeFrame: 30 days after surgery
measure: Complication severity
timeFrame: 30 days after surgery
measure: Proportion of patients returning to preoperative functional walking capacity
timeFrame: 30 days after surgery
measure: Self-reported activity status and generic health related quality of life
timeFrame: 30 days after surgery
Other outcomes:
Locations:
city: Catanzaro
country: Italy
facility: Policlinico Universitario AOU Renato Dulbecco di Catanzaro
city: Firenze
country: Italy
facility: AOU Careggi
city: Genova
country: Italy
facility: Ospedale Galliera di Genova
city: Milano
country: Italy
facility: ASSTN GOM Niguarda
city: Milan
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Monza
country: Italy
facility: IRCCS Ospedale San Gerardo dei Tintori
city: Napoli
country: Italy
facility: Ospedale Vanvitelli di Napoli
city: Padova
country: Italy
facility: AOPD Padova
city: Udine
country: Italy
facility: Azienda sanitaria universitaria Friuli Centrale (ASU FC)
Study officials:
affiliation: IRCCS Ospedale San Raffaele
name: Marina Pieri, Medical Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Colado JC, Pedrosa FM, Juesas A, Gargallo P, Carrasco JJ, Flandez J, Chupel MU, Teixeira AM, Naclerio F. Concurrent validation of the OMNI-Resistance Exercise Scale of perceived exertion with elastic bands in the elderly. Exp Gerontol. 2018 Mar;103:11-16. doi: 10.1016/j.exger.2017.12.009. Epub 2017 Dec 17.
citation: Levett DZH, Jack S, Swart M, Carlisle J, Wilson J, Snowden C, Riley M, Danjoux G, Ward SA, Older P, Grocott MPW; Perioperative Exercise Testing and Training Society (POETTS). Perioperative cardiopulmonary exercise testing (CPET): consensus clinical guidelines on indications, organization, conduct, and physiological interpretation. Br J Anaesth. 2018 Mar;120(3):484-500. doi: 10.1016/j.bja.2017.10.020. Epub 2017 Nov 24.
citation: Molenaar CJ, van Rooijen SJ, Fokkenrood HJ, Roumen RM, Janssen L, Slooter GD. Prehabilitation versus no prehabilitation to improve functional capacity, reduce postoperative complications and improve quality of life in colorectal cancer surgery. Cochrane Database Syst Rev. 2022 May 19;5(5):CD013259. doi: 10.1002/14651858.CD013259.pub2.
citation: Silver JK, Baima J. Cancer prehabilitation: an opportunity to decrease treatment-related morbidity, increase cancer treatment options, and improve physical and psychological health outcomes. Am J Phys Med Rehabil. 2013 Aug;92(8):715-27. doi: 10.1097/PHM.0b013e31829b4afe.
citation: Lemanne D, Cassileth B, Gubili J. The role of physical activity in cancer prevention, treatment, recovery, and survivorship. Oncology (Williston Park). 2013 Jun;27(6):580-5.
citation: Carli F. Physiologic considerations of Enhanced Recovery After Surgery (ERAS) programs: implications of the stress response. Can J Anaesth. 2015 Feb;62(2):110-9. doi: 10.1007/s12630-014-0264-0. Epub 2014 Dec 12.