Immediate Curative Vs Conservative Treatment in Older Men with M0, High-risk Prostate Cancer

Phase 3

Recruiting

• Conditions: Prostate Cancer
• Interventions: Radiation: Radiotherapy or surgery; Other: initial observation; Drug: Hormone therapy

• Registration Number: NCT05448547
• Lead Sponsor: Sven Löffeler

Brief Summary

It is currently unclear if immediate curative treatment (radiotherapy or surgery) of high-risk prostate cancer without metastasis in older men (\>=75 years) generates the same survival benefits as in younger patients or if the harms/ side-effects of immediate curative treatment outweigh the benefits. In this study the investigators randomize older patients with high-risk, non-metastatic high-risk prostate cancer to either immediate curative therapy or to conservative, more problem-oriented therapy to investigate if immediate curative treatment prolongs life, improves quality of life and is cost-effective.

Detailed Description

There is a lack of both level 1 evidence and consensus regarding the optimal treatment strategy for older men (\>=75 years) with non-metastatic, high-risk prostate cancer. Currently, in Scandinavia, the majority of older patients are treated conservatively, i.e. with hormone therapy or watchful waiting while some centers recommend immediate curative therapy regardless of patient age. Older patients thus risk both undertreatment and overtreatment of their cancer. This randomized clinical trial investigates if immediate curative therapy of high-risk, non-metastatic prostate cancer prolongs life (as it does in younger patients) and improves health-related quality of life. Furthermore, this trial investigates if the early side effects of immediate curative therapy are compensated by better long-term tumor control, better quality of life, functional status and improved survival.

Study Timeline

• Study First Submitted: 2022-06-22
• Study First Submitted QC: 2022-07-02
• Study First Posted: 2022-07-07
• Study Start: 2022-11-04
• Status Verified: 2024-09
• Last Update Submitted: 2024-09-30
• Last Update Posted: 2024-10-02
• Primary Completion: 2029-12-31
• Study Completion: 2036-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 980

Inclusion Criteria

1. Participant must be 75 years of age or older, at the time of signing the informed consent.

2. Participants who are healthy as determined by medical evaluation and geriatric G8/ miniCOGTM evaluation (G8: Fit, score >14, or reversibly frail; miniCOGTM: score >2)

   And who have PCa (diagnosed ≤6 months) with one or both of the following features:

   • Gleason grade 8-10 (ISUP group 4 and 5) other than microscopic, low-volume disease (tumor must be either palpable or visible on MRI, i.e., PIRADS 4 or 5)
   • Locally advanced PCa (T3 or T4) (unequivocal findings of clinical/ radiological T3 or clinical/ radiological T4 on DRE or MRI; broad capsular contact of tumor on MRI is treated as localized disease, T2, in the context of this study)
   • Able to read, understand and fill in HRQoL questionnaires (PROMS)

3. Male

4. Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria

Medical Conditions

1. Dementia (unable to consent) Prior/Concomitant Therapy

2. Prior radiation to the pelvis

3. Hormone therapy >3 months prior to randomization Diagnostic assessments

4. Lymph node metastasis (N0) on MRI, CT or PSMA-PET CT (equivocal N-findings =N0; borderline cases will be discussed and called by a study tumor board).

5. Distant metastasis (M0) on MRI, CT, bone scan or PSMA-PET CT (equivocal bone scan findings need to be confirmed with MRI or CT; borderline cases will be discussed by a study tumor board).

   Other Exclusions

6. Disabled or severe comorbidity (identified by G8 screening)

7. Unable to read, understand or fill out HRQoL questionnaires (PROMS)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
immediate curative therapy	Radiotherapy or surgery	Patients randomized to the intervention arm will receive immediate curative therapy in the form of either radiotherapy to the prostate in combination with hormone therapy (ADT or monotherapy) or surgery (radical prostatectomy). Standard treatment in this arm is radiotherapy + hormone therapy. Surgery is reserved for patients with strong preferences against radiotherapy.
initial observation/ hormone therapy	initial observation	Patients in this arm will either be observed (with localized high-risk prostate cancer) or receive hormone therapy (locally advanced prostate cancer; ADT or monotherapy). Further local or systemic therapy is given at doctor's discretion triggered by local or/ and systemic progression.
initial observation/ hormone therapy	Hormone therapy	Patients in this arm will either be observed (with localized high-risk prostate cancer) or receive hormone therapy (locally advanced prostate cancer; ADT or monotherapy). Further local or systemic therapy is given at doctor's discretion triggered by local or/ and systemic progression.

Primary Outcome Measures

Name	Time	Method
Overall survival	10 years following end of recruitment	overall survival
Burden of disease	0-10 years	European Organisation for Research and Treatment of Cancer questionnaire for assessment of health-related quality of life elderly patients with cancer (EORTC ELD 14), burden of disease scale (2 questions, score 0-100, high scores indicate high burden of disease)

Secondary Outcome Measures

Name	Time	Method
Prostate cancer morbidity	0-10 years	hospitalizations, interventions, complications due to local progression/ systemic progression)
Role functioning	0-10 years	European Organisation for Research and Treatment of Cancer questionnaire for quality of life of cancer patients (EORTC-QLQ-C30), RF2 scale (2 questions, score 0-100, high scores indicate a high / healthy level of functioning)
bowel symptoms	0-10 years	Expanded Prostate Cancer Index Composite Short Form questionnaire (EPIC-26), bowel scales (score 0-100, higher scores indicating better outcomes)
Urinary irritative/ obstructive symptoms	0-10 years	Expanded Prostate Cancer Index Composite Short Form questionnaire (EPIC-26),urinary scales (score 0-100, higher scores indicating better outcomes)
Prostate-cancer-specific survival	0-10 years	Prostate cancer deaths in intervention and control group
Metastasis-free survival	0-10 years	time to metastasis detected radiographically due to symptoms or biochemical progression
Symptom-/ intervention-free survival	0-10 years	time to symptoms/ need for interventions due to prostate cancer progression
Quality of life-adjusted years	0-10 years	Euro QoL group questionaire (EQ-5D-5L) (1 =full health; 0= dead)
need for secondary and tertiary therapy	0-10 years	use of second- and third-line therapies

Trial Locations

Locations (17)

Helsinki University Hospital; 🇫🇮 Helsinki, Finland

Turku University Hospital; 🇫🇮 Turku, Finland

Telemark Hospital Trust; 🇳🇴 Skien, Telemark, Norway

Vestre Viken Hospital Trust; 🇳🇴 Drammen, Norway

Capio Saint Göran's Hospital; 🇸🇪 Stockholm, Sweden

Rigshospital; 🇩🇰 Copenhagen, Denmark

Odense University Hospital; 🇩🇰 Odense, Denmark

Tampere University Hospital; 🇫🇮 Tampere, Finland

Sunmøre Hospital Trust; 🇳🇴 Ålesund, Møre og Romsdal, Norway

Stavanger University Hospital; 🇳🇴 Stavanger, Rogaland, Norway

Sørlandet Hospital Trust; 🇳🇴 Kristiansand, Sørlandet, Norway

St. Olavs Hospital; 🇳🇴 Trondheim, Trøndelag, Norway

Vestfold Hospital Trust (Hospital of Vestfold); 🇳🇴 Tønsberg, Vestfold, Norway

Innlandet Hospital Trust; 🇳🇴 Hamar, Norway

Akerhus University Hospital; 🇳🇴 Lørenskog, Norway

Oslo University Hospital; 🇳🇴 Oslo, Norway

University Hospital of Northern Norway; 🇳🇴 Tromsø, Norway