Multimodal Prehabilitation in Cancer Surgery (PROPOSE-RCT)

Multimodal Prehabilitation in Cancer Surgery PROPOSE Trial (PRehabilitation in Oncological Patients undergOing SurgEry): A Randomized Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Cancer Surgery
• Intervention / Treatment: Behavioral: Multimodal prehabilitation Program

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

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marina LG Pieri, Medical Doctor; Phone Number: +393334625052; Email: pieri.marina@hsr.it

Study Locations

• Italy
  • Catanzaro, Italy, 88100
    • Recruiting
    • Policlinico Universitario AOU Renato Dulbecco di Catanzaro
    • Contact: Eugenio Garofalo, Professor; Phone Number: +393498125841; Email: eugenio.garofalo@gmail.com
  • Firenze, Italy, 50134
    • Not yet recruiting
    • AOU Careggi
    • Contact: Gabriele Baldini, Professor; Phone Number: +393333196036; Email: gabriele.baldini@unifi.it
  • Genova, Italy, 16128
    • Not yet recruiting
    • Ospedale Galliera di Genova
    • Contact: Claudia Brusasco, Doctor; Phone Number: +393291185009; Email: claudia.brusasco@gmail.com
  • Milan, Italy, 20132
    • Recruiting
    • IRCCS Ospedale San Raffaele
    • Contact: Marina Pieri, MD; Phone Number: +39 0226438173; Email: pieri.marina@hsr.it
    • Principal Investigator: Marina Pieri, MD
  • Milano, Italy, 20162
    • Not yet recruiting
    • ASSTN GOM Niguarda
    • Contact: Monica Gualtierotti, Doctor; Phone Number: +390264447918; Email: monica.gualtierotti@ospedaleniguarda.it
  • Monza, Italy, 20900
    • Not yet recruiting
    • IRCCS Ospedale San Gerardo dei Tintori
    • Contact: Luca C Nespoli, Professor; Phone Number: +393201797391; Email: luca.nespoli@unimib.it
  • Napoli, Italy, 80129
    • Recruiting
    • Ospedale Vanvitelli di Napoli
    • Contact: Pasquale Sansone, Professor; Phone Number: +393384969395; Email: pasquale.sansone@unicampania.it
  • Padova, Italy, 35128
    • Not yet recruiting
    • AOPD Padova
    • Contact: Nicola Passuello, Doctor; Phone Number: +393482245159; Email: nicola.passuello@aopd.veneto.it
  • Udine, Italy, 33100
    • Not yet recruiting
    • Azienda Sanitaria Universitaria Friuli Centrale (ASU FC)
    • Contact: Tiziana Bove, Professor; Phone Number: +393474785763; Email: tiziana.bove@asufc.sanita.fvg.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control group; Standard care treatment with application of ERAS pathways (Enhanced Recovery After Surgery)
Experimental: Prehabilitation; The prehabilitation arm group will receive preoperative intervention which includes exercise training, nutritional therapy and anxiety reducing techniques, aimed at preventing or attenuating surgery-driven functional decline. This will be on top of Standard care treatment with application of ERAS pathways (Enhanced Recovery After Surgery).	Behavioral: Multimodal prehabilitation Program; A tailored intervention will be prescribed if specific physical, nutritional or psychological impairments will be identified during the assessment phase. Based on the data obtained during the multimodal assessment, different domains and levels of care will be prescribed, focusing on exercise training, and/or nutrition optimization, and/or distress-coping techniques. Different combinations of three domains will be utilized to maximize their synergistic anabolic effects. The duration of the program will be set at a minimum of three weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the impact of prehabilitation on severe postoperative complications among high-risk patients undergoing oncological surgery	The proportion of patients experiencing severe postoperative complications within 30 days after surgery defined as grade 3a or greater according to the Clavien-Dindo classification	30 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Functional Recovery (TFR)	Faster return to basal functional preoperative capacity in treatment group	30 days after surgery
Lenght of hospital stay (LOS)	Reduction of lenght of hospital stay in treatment group	30 days after surgery
Days at home up to 30 days after surgery (DAH-30)	The mean number of days at home in the first 30 days after surgery will be compared between groups	30 days after surgery
Complication severity	Assess complication severity as measured by the Comprehensive Complication Index (CCI)	30 days after surgery
Proportion of patients returning to preoperative functional walking capacity	Improvement in the return to basal functional preoperative capacity	30 days after surgery
Self-reported activity status and generic health related quality of life	Assess quality of life in the first 30 days at home after surgery using the EuroQol-5 Dimension (EQ-5D-5L) questionnaire, a validated tool for evaluating health-related quality of life. The outcome will be reported as the mean EQ-5D-5L index score and the mean EQ-VAS score measured at 30 days postoperatively.	30 days after surgery

Collaborators and Investigators

• Sponsor: Università Vita-Salute San Raffaele
• Collaborators: Prof. Pasquale Sansone; Prof. Eugenio Garofalo; Prof. Tiziana Bove; Dr. Claudia Brusasco; Prof. Gabriele Baldini; Dr. Nicola Passuello; Dr. Monica Gualtierotti; Prof. Luca Carlo Nespoli
• Investigators: Principal Investigator: Marina Pieri, Medical Doctor, IRCCS Ospedale San Raffaele

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: January 17, 2025
• First Submitted That Met QC Criteria: January 22, 2025
• First Posted (Actual): January 23, 2025

Study Record Updates

• Last Update Posted (Actual): August 7, 2025
• Last Update Submitted That Met QC Criteria: August 5, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Exercise; Nutrition; Relaxation; Diet; Prehabilitation; Functional recovery; Hospital stay; Anesthesiology; Standard treatment; Multimodal prehabilitation program; Functional walking
• Other Study ID Numbers: PNRR-MCNT2-2023-12378183

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No