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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Prostate Cancer; Erectile Dysfunction Following Radical Prostatectomy; Urinary Incontinence Following Surgical Procedure
• Intervention / Treatment: Drug: Tadalafil 5 mg; Behavioral: Pelvic Floor Muscle Training (PFMT); Behavioral: Aerobic Exercise Program; Behavioral: Nutritional Recommendations; Behavioral: Psychological and Wellbeing Strategies; Behavioral: Standard Perioperative Care

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Nicholas Hirst; Phone Number: +61 2 9515 3200; Email: Nicholas.Hirst1@health.nsw.gov.au
• Study Contact Backup: Name: SOuRCe Admin; Email: SLHD-SOuRCe@health.nsw.gov.au

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2050
      • Chris O'Brien Lifehouse
      • Contact: Nicholas Hirst; Phone Number: +61 2 9515 3211; Email: nicholas.hirst1@health.nsw.gov.au
    • Sydney, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
      • Contact: Nicholas Hirst; Phone Number: +61 2 9515 3211; Email: nicholas.hirst1@health.nsw.gov.au
    • Sydney, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital (CRGH)
      • Contact: Nicholas Hirst; Phone Number: +61 2 9515 3211; Email: nicholas.hirst1@health.nsw.gov.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Multimodal Prehabilitation and Rehabilitation plus standard care; Participants receive standard care PLUS a multimodal program commencing ≥4 weeks preoperatively and continuing for 3 months postoperatively (following catheter removal). The program comprises four components: (1) tadalafil 5 mg orally once daily (paused during hospital admission); (2) pelvic floor muscle training 3 sets/day; (3) aerobic exercise 40 min, 4×/week; (4) nutritional guidance; and (5) psychological/wellbeing strategies. All non-pharmacological components are self-directed and digitally delivered.	Drug: 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.; Other Names: Tadalafil GH; Behavioral: 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.; Behavioral: 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.; Behavioral: 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.; Behavioral: 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 by a clinical psychologist and delivered via digital booklet and videos. Commenced 4 weeks preoperatively, continuing through 3 months postoperatively.; Behavioral: 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.
Active Comparator: Standard Care; Participants receive usual high-standard perioperative care from their treating team, including clinical advice on exercise, nutrition, smoking cessation, alcohol reduction, expected surgical sequelae, and pelvic floor exercises, as well as medical considerations (blood sugar optimisation, medication review, anaemia screening). Prostate cancer nurse specialist consultations and urology clinic attendance are included as standard.	Behavioral: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Erectile Function - International Index of Erectile Function-5 (IIEF-5)	The IIEF-5 is a validated 5-item self-report questionnaire assessing erectile function over the preceding 4 weeks. Scores range from 5 (severe erectile dysfunction) to 25 (no erectile dysfunction). A between-group difference of ≥4 points constitutes the minimal clinically important difference (MCID) as established by Rosen et al. (2011). The IIEF-5 is the abbreviated version of the 15-item IIEF, widely used in prostate cancer rehabilitation trials.	Assessed at 3 months postoperatively (primary endpoint). Also assessed at baseline (4 weeks preoperatively), 6 weeks, 6 months, and 12 months postoperatively.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary Incontinence - ICIQ-UI SF	The International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) is a validated 4-item patient-reported measure of urinary incontinence severity and impact on quality of life. Scores range from 0 (no incontinence) to 21 (severe incontinence). Assesses urinary leakage frequency, volume, and overall impact.	Baseline (≥4 weeks preoperatively), 6 weeks, 3 months, 6 months, and 12 months postoperatively.
Number of Urinary Pads Used in 24 Hours	Total number of urinary pads used by the participant over a 24-hour period, as self-reported. A higher number of pads indicates greater urinary incontinence severity.	Baseline, 6 weeks, 3 months, 6 months, and 12 months postoperatively.
Weight of Urinary Pads Used in 24 Hours	Total weight (grams) of urinary pads used over a 24-hour period. Pad weight is obtained by weighing pads before and after use and calculating the difference. Higher weight indicates greater urine leakage volume.	Baseline, 6 weeks, 3 months, 6 months, and 12 months postoperatively.
Maximum Urinary Flow Rate (Uroflowmetry - Q-max)	Maximum urinary flow rate (mL/s) measured by uroflowmetry during voiding. Higher values indicate better bladder outflow function.	Baseline, 6 weeks, 3 months, 6 months, and 12 months postoperatively.
Post-Void Residual Urine Volume	Volume of urine remaining in the bladder after voiding (mL), measured by bladder ultrasound or catheterisation. Lower post-void residual volumes indicate more complete bladder emptying.	Baseline, 6 weeks, 3 months, 6 months, and 12 months postoperatively.
Maximum Detrusor Pressure (Urodynamics)	Maximum detrusor pressure (cmH₂O) measured during urodynamic testing, reflecting bladder contractility and outflow resistance during voiding.	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)	The Short Form-36 Health Survey, Version 2 (SF-36v2) is a validated 36-item multidimensional self-report questionnaire assessing health-related quality of life across eight domains: physical functioning, role limitations due to physical health, role limitations due to emotional health, bodily pain, general health perceptions, vitality, social functioning, and mental health. Each domain score ranges from 0 to 100, with higher scores indicating better health-related quality of life in that domain. Physical Component Summary (PCS) and Mental Component Summary (MCS) scores are derived (each ranging from 0 to 100; higher scores indicate better health).	Baseline, 6 weeks, and 6 months postoperatively.
Anxiety and Depression - Hospital Anxiety and Depression Scale (HADS)	The HADS is a validated 14-item self-report questionnaire with two 7-item subscales assessing anxiety (HADS-A) and depression (HADS-D) severity. Each subscale is scored 0-21; scores ≥8 indicate probable caseness. Designed for use in medical settings with somatic symptoms excluded to avoid confounding.	Baseline, 6 weeks, 3 months, 6 months, and 12 months postoperatively.
Fear of Cancer Recurrence - Single-Item Scale (FCR-1)	A single-item 0-10 numerical rating scale measuring fear of cancer recurrence. Scores range from 0 (no fear) to 10 (maximum fear of recurrence), with higher scores indicating greater fear of cancer recurrence. This single-item scale has been demonstrated as equivalently effective to the short-form FCR scale in oncological populations.	Baseline, 6 weeks, 3 months, 6 months, and 12 months postoperatively.
Pain Intensity - Numeric Pain Rating Scale (NPRS)	The NPRS is a single-item 0-10 scale measuring current pain intensity (0 = no pain, 10 = worst imaginable pain). Widely used in surgical and oncological populations.	Baseline, 6 weeks, 3 months, 6 months, and 12 months postoperatively.
Postoperative Complication Rate - Clavien-Dindo Classification of Surgical Complications	Proportion of participants developing postoperative surgical complications within 30 days of surgery, categorised under the Clavien-Dindo Classification of Surgical Complications. Grades range from I (minor complication requiring no specific treatment beyond standard medications) to V (death). Higher grades indicate more severe complications and represent a worse outcome. Assessed by the treating clinical team from medical records.	Within 30 days postoperatively. Complications also monitored at 6 weeks, 3 months, 6 months, and 12 months.
Length of Hospital Stay	Total number of days from RARP surgery to hospital discharge, extracted from medical records.	At hospital discharge (postoperative), assessed up to approximately 5 days.
Positive Surgical Margin Rate	Proportion of participants with histopathologically confirmed positive surgical margins on surgical pathology report. A positive surgical margin indicates residual tumour at the resection edge and represents an adverse oncological outcome.	Following surgical pathology report, assessed within approximately 4 weeks of surgery.
Pathological Staging - Tumour, Node, Metastasis (TNM) Classification	Pathological TNM stage assigned from the surgical pathology report according to the Union for International Cancer Control (UICC) TNM classification system. Staging reflects the pathological extent of disease including primary tumour (T), regional lymph nodes (N), and distant metastases (M). Higher pathological stage indicates more locally advanced disease.	Following surgical pathology report, assessed within approximately 4 weeks of surgery.
Tumour Grade - Gleason Score and International Society of Urological Pathology (ISUP) Grade Group	Gleason score (range 6-10; higher scores indicate less differentiated, more aggressive tumour histology) and International Society of Urological Pathology (ISUP) Grade Group (range 1-5; higher grade groups indicate more aggressive disease and a worse prognosis). Both are derived from the surgical pathology report and are reported together as they describe the same histopathological characteristic.	Following surgical pathology report, assessed within approximately 4 weeks of surgery.
Adverse Pathological Features: Seminal Vesicle Invasion, Perineural Invasion, and Extraprostatic Extension	Proportion of participants with each of the following adverse pathological features identified on surgical pathology report: (1) seminal vesicle invasion (SVI - yes/no), (2) perineural invasion (PNI - yes/no), and (3) extraprostatic extension (EPE - yes/no). Each is reported as a proportion (%). Presence of these features indicates more locally advanced pathology and is associated with poorer oncological outcomes.	Following surgical pathology report, assessed within approximately 4 weeks of surgery.
Incremental Cost-Effectiveness - Cost per IIEF-5 Improvement	Economic analysis estimating the incremental cost per point improvement in IIEF-5 score for the multimodal program versus standard care. Costing data will include inpatient hospitalisation costs (from SLHD Performance Unit), out-of-pocket participant costs (reimbursed medication), and research-related resource utilisation.	At 6 months postoperatively.
Implementation Evaluation - RE-AIM Framework	The RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework will be applied by investigators to evaluate the implementation of the trial, including reach of the eligible population, fidelity of intervention delivery, and potential for future adoption in clinical settings. Assessed via a structured investigator-completed survey.	At trial completion (approximately 6 months postoperative of final participant).
Acceptability of the Multimodal Program to Participants	Assessed via a structured qualitative survey (Likert-scale and open-ended questions) and semi-structured interviews with intervention arm participants. Explores barriers and facilitators to engagement, satisfaction with the program, and experiences with pharmacological adherence including pharmacy logistics. Qualitative free-text data will be analysed using reflexive thematic analysis. This is a qualitative outcome and is not scored on a numerical scale.	Following completion of the prehabilitation program, assessed at approximately 3 months postoperatively.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical Activity Level - International Physical Activity Questionnaire (IPAQ)	The International Physical Activity Questionnaire (IPAQ) is a validated self-report questionnaire measuring total physical activity across four domains (work, transport, domestic, and leisure) over the preceding 7 days. Total physical activity is expressed as metabolic equivalent of task minutes per week (MET-minutes/week). There is no defined upper limit to the score; higher values indicate greater levels of physical activity, which represents a better outcome.	Baseline and 3 months postoperatively
Intensive Care Unit (ICU) Admission Rate	Proportion of participants admitted to the intensive care unit (ICU) during their postoperative hospital stay following RARP, extracted from medical records.	At hospital discharge (postoperative), assessed up to approximately 5 days.
Intensive Care Unit (ICU) Length of Stay	Total duration of ICU admission (hours) for participants admitted to the ICU postoperatively, extracted from medical records. Assessed only in the subset of participants admitted to the ICU.	At hospital discharge (postoperative), assessed up to approximately 5 days.
30-Day Hospital Readmission Rate	Proportion of participants admitted to hospital within 30 days of RARP surgery, for any cause. Assessed via participant self-report and medical records.	6-week postoperative assessment (capturing 30-day window).
Prostate Specific Antigen (PSA)	Serum PSA (ng/mL) extracted from medical records or pathology results.	Baseline (preoperative), 6 weeks, 3 months, 6 months, and 12 months postoperatively.

Collaborators and Investigators

• Sponsor: Surgical Outcomes Research Centre (SOuRCe)
• Collaborators: National Health and Medical Research Council, Australia; Sydney Local Health District; Generic Health
• Investigators: Principal Investigator: Daniel Steffens, Surgical Outcomes Research Centre (SOuRCe)

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: April 22, 2026
• First Submitted That Met QC Criteria: May 4, 2026
• First Posted (Actual): May 8, 2026

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: rehabilitation; prostate cancer; erectile dysfunction; prehabilitation; urinary incontinence; perioperative care; tadalafil; PDE5 inhibitor; robot-assisted radical prostatectomy; pelvic floor muscle training; multimodal intervention; sexual rehabilitation
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Mental Disorders; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urination Disorders; Lower Urinary Tract Symptoms; Urological Manifestations; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Prostatic Neoplasms; Urinary Incontinence; Erectile Dysfunction; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indoles; Indole Alkaloids; Heterocyclic Compounds, 3-Ring; Carbolines; Tadalafil
• Other Study ID Numbers: X26-0106; CH62/6/2026-007 (Other Identifier: SLHD CRGH HREC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to make individual participant data available to other researchers. All data will be stored securely for 15 years following trial closure in accordance with ICH-GCP, TGA, and HREC requirements. Aggregate de-identified results will be disseminated via peer-reviewed publications and conference presentations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No