Multimodal Prehabilitation and Rehabilitation for Men Undergoing Robot-Assisted Radical Prostatectomy

Официальное название

Multimodal Perioperative Optimisation for Patients Undergoing Robot-Assisted Radical Prostatectomy: A Randomised Controlled Trial Targeting Postoperative Erectile Dysfunction (ROBOPREP Trial)

Обзор

Prostate cancer is the most common cancer in Australian men. Robot-assisted radical prostatectomy (RARP) - surgical removal of the prostate - is a standard treatment, but it frequently causes erectile dysfunction (ED) and urinary incontinence that can persist for years and significantly affect quality of life. This trial (ROBOPREP) will test whether a multimodal program of prehabilitation (before surgery) and rehabilitation (after surgery) improves erectile function and urinary continence in men undergoing RARP, compared to standard care alone. The program includes four components, all delivered virtually and in a self-directed manner: 1. Pharmacological - tadalafil 5 mg once daily (a low-dose, TGA-approved erectile medication) beginning 4 weeks before surgery, paused during hospital admission, and resumed for 3 months following catheter removal after surgery. 2. Exercise - pelvic floor muscle training (3 sets per day) and aerobic exercise (40 minutes, 4 times per week) to strengthen the muscles and vascular supply involved in erectile and urinary function. 3. Nutrition - dietary guidance to support surgical recovery and vascular health. 4. Psychological/wellbeing - relaxation techniques, psychoeducation about expected recovery, and self-compassion strategies to address cancer-related anxiety. A total of 64 men will be recruited across three major Sydney hospitals (Royal Prince Alfred Hospital, Concord Repatriation General Hospital, and Chris O'Brien Lifehouse) and randomly assigned 1:1 to the multimodal program plus standard care, or to standard care alone. Outcomes - including erectile function (primary), urinary continence, quality of life, and psychological wellbeing - are assessed at baseline and at 6 weeks, 3, 6, and 12 months following surgery. All participant-facing elements of the program are digital, low-cost, and designed for real-world scalability.

Подробное описание

The ROBOPREP Trial is a hybrid type 1 multicentre, assessor-blinded, parallel-group randomised controlled trial with nested qualitative and cost-effectiveness appraisal. The trial evaluates a virtually delivered, self-directed multimodal (p)rehabilitation program for men undergoing robot-assisted radical prostatectomy (RARP) for prostate cancer.

Background: Erectile dysfunction (ED) occurs in 25-75% of men following RARP, with unassisted recovery of erectile function in only 20-25%. Urinary incontinence affects a further 27-40%. Current evidence supports early initiation of phosphodiesterase type 5 inhibitors (PDE5i), pelvic floor muscle training (PFMT), and psychological interventions, but no multimodal perioperative program combining all modalities has been evaluated in a rigorous RCT.

Intervention: Participants randomised to the intervention arm receive, in addition to standard care: (1) tadalafil 5 mg/day orally commencing 4 weeks preoperatively, ceasing during hospital admission, and resuming for 3 months following postoperative catheter removal; (2) pelvic floor muscle training (3 sets/day: 20 fast and 20 slow contractions); (3) aerobic exercise (40 min, 4×/week, moderate-to-vigorous intensity); (4) nutritional guidance; and (5) psychological strategies including relaxation, psychoeducation, and self-compassion. Non-pharmacological components are delivered via a co-designed digital booklet and avatar videos. All components are self-directed to ensure scalability.

Randomisation and Blinding: Randomisation (1:1, stratified by age ≤60 vs \>60 years, permuted blocks of size 2 and 4) is managed via a central secure REDCap randomisation module uploaded by an independent research officer. Outcome assessors are blinded to allocation; blinding of participants and treating clinicians is not feasible given the nature of the intervention.

Statistical Analysis: Primary analysis is intention-to-treat. The primary outcome (IIEF-5 at 3 months postoperatively) will be compared between arms using Mann-Whitney U tests and multivariate regression adjusting for baseline characteristics. Secondary outcomes will be analysed using mixed models, Cox regression (time to continence), and chi-square or Fisher's exact tests as appropriate.

The trial medication is funded by Generic Health (Lupin), who provide a donation covering participant reimbursement for tadalafil 5 mg (4-month supply; approx. AUD $120-150 per participant) and the TGA CTN application fee. Tadalafil 5 mg is TGA-approved for erectile dysfunction (ARTG: 289541).

Вмешательства

• Препарат Tadalafil 5 mg
  Tadalafil 5 mg tablet, taken orally once daily. Commenced 4 weeks prior to surgery, ceased during hospital admission (3 days prior to surgery), and recommenced following postoperative urinary catheter removal (typically 5-10 days post-surgery) for 3 months. Total intended duration approximately 4 months. Supplied via standard prescription dispensing at community pharmacies (Generic Health brand). Reimbursement provided to participants via a cash card. TGA ARTG number: 289541.
• Поведенческое Pelvic Floor Muscle Training (PFMT)
  Self-directed PFMT performed 3 sets per day. Each set comprises 20 fast contractions (1-second duration) and 20 slow contractions (10 seconds on, 10 seconds off). Adapted from Milios et al. (2020) using Continence Australia guidelines. Delivered via co-designed digital booklet and avatar instructional videos. Commenced 4 weeks preoperatively, continuing through 3 months postoperatively.
• Поведенческое Aerobic Exercise Program
  Self-directed aerobic exercise at moderate-to-vigorous intensity (e.g., brisk walking while able to maintain conversation), 40 minutes per session, 4 sessions per week. Dose established by Gerbild et al. (2018). Delivered via digital booklet and avatar videos. Commenced 4 weeks preoperatively, continuing through 3 months postoperatively.
• Поведенческое Nutritional Recommendations
  Structured dietary guidance addressing protein intake, fruit and vegetable consumption, wholegrains, healthy fats, hydration, and blood sugar control. Designed by a dietitian to support surgical healing, vascular health, and erectile and urinary function recovery. Delivered via digital booklet and avatar videos. Commenced 4 weeks preoperatively, continuing through 3 months postoperatively.
• Поведенческое Psychological and Wellbeing Strategies
  Self-directed psychological wellbeing program comprising: (1) relaxation techniques (progressive muscle relaxation, diaphragmatic/rectangle breathing, mindfulness/grounding); (2) psychoeducation on psychogenic erectile dysfunction, expected postoperative complications (ED, UI); (3) self-compassion and cognitive reframing strategies; (4) motivational interviewing-style elements to support adherence; (5) advice on social connection, smoking cessation, alcohol reduction, and sleep hygiene. Designed
• Поведенческое Standard Perioperative Care
  Usual high-standard pre- and postoperative care delivered by the treating urological team, including clinical advice on exercise, nutrition, smoking cessation, alcohol reduction, expected surgical sequelae, pelvic floor exercises, blood sugar optimisation, medication review, and anaemia screening. Includes prostate cancer nurse specialist consultations and urology clinic follow-up.

Первичные конечные точки

• Erectile Function - International Index of Erectile Function-5 (IIEF-5) [Срок оценки: Assessed at 3 months postoperatively (primary endpoint). Also assessed at baseline (4 weeks preoperatively), 6 weeks, 6 months, and 12 months postoperatively.]

Вторичные конечные точки (12)

• Urinary Incontinence - ICIQ-UI SF [Срок оценки: Baseline (≥4 weeks preoperatively), 6 weeks, 3 months, 6 months, and 12 months postoperatively.]
• Number of Urinary Pads Used in 24 Hours [Срок оценки: Baseline, 6 weeks, 3 months, 6 months, and 12 months postoperatively.]
• Weight of Urinary Pads Used in 24 Hours [Срок оценки: Baseline, 6 weeks, 3 months, 6 months, and 12 months postoperatively.]
• Maximum Urinary Flow Rate (Uroflowmetry - Q-max) [Срок оценки: Baseline, 6 weeks, 3 months, 6 months, and 12 months postoperatively.]
• Post-Void Residual Urine Volume [Срок оценки: Baseline, 6 weeks, 3 months, 6 months, and 12 months postoperatively.]
• Maximum Detrusor Pressure (Urodynamics) [Срок оценки: Baseline, 6 weeks, 3 months, 6 months, and 12 months postoperatively.]
• Health-Related Quality of Life - Short Form-36 Health Survey, Version 2 (SF-36v2) [Срок оценки: Baseline, 6 weeks, and 6 months postoperatively.]
• Anxiety and Depression - Hospital Anxiety and Depression Scale (HADS) [Срок оценки: Baseline, 6 weeks, 3 months, 6 months, and 12 months postoperatively.]
• Fear of Cancer Recurrence - Single-Item Scale (FCR-1) [Срок оценки: Baseline, 6 weeks, 3 months, 6 months, and 12 months postoperatively.]
• Pain Intensity - Numeric Pain Rating Scale (NPRS) [Срок оценки: Baseline, 6 weeks, 3 months, 6 months, and 12 months postoperatively.]
• Postoperative Complication Rate - Clavien-Dindo Classification of Surgical Complications [Срок оценки: Within 30 days postoperatively. Complications also monitored at 6 weeks, 3 months, 6 months, and 12 months.]
• Length of Hospital Stay [Срок оценки: At hospital discharge (postoperative), assessed up to approximately 5 days.]

Критерии участия

Критерии включения

• Adults aged ≥18 years undergoing elective robot-assisted radical prostatectomy (RARP) with curative intent for confirmed prostate cancer.
• Consulting a urological surgeon with an appointment at participating sites at least 4 weeks prior to scheduled surgery.
• Willingness to engage in prescribed self-directed interventions.

Критерии исключения

• Cognitive impairment such that they lack capacity to provide informed consent.
• Currently taking intracavernosal injection therapy.
• Severe or complete erectile dysfunction at baseline, defined as an IIEF-5 score ≤7 or self-reported absence of erectile function.
• Prescribed nitrates or guanylate cyclase stimulators (e.g., riociguat) - pharmacological contraindication to PDE5 inhibitor use.
• Impaired renal function (GFR <50 mL/min and/or creatinine clearance <30 mL/min).
• Severe hepatic impairment or concurrent prescription of medications that inhibit CYP3A4.
• Loss of vision in one eye due to non-arteritic anterior ischaemic optic neuropathy (NAION).
• Myocardial infarction within the last 90 days.
• Stroke within the last 6 months.
• Unstable angina or angina occurring during sexual intercourse.
• New York Heart Association (NYHA) Class II or greater heart failure in the last 6 months.
• Uncontrolled arrhythmias, hypotension (<90/50 mmHg), or uncontrolled hypertension.
• Contraindications to participating in the prescribed exercise program.
• No access to a device with internet connectivity.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Австралия · 3 центра

• Chris O'Brien Lifehouse — Sydney
• Royal Prince Alfred Hospital — Sydney
• Concord Repatriation General Hospital (CRGH) — Sydney

Идентификаторы

NCT: NCT07576335 · X26-0106 · CH62/6/2026-007

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗