Immediate Curative vs Conservative Treatment in Older Men With M0, High-risk Prostate Cancer (GrandP/SPCG19)

Sven Löffeler

Status and phase: Enrolling; Phase 3

Conditions: Prostate Cancer

Treatments: Drug: Hormone therapy; Other: initial observation; Radiation: Radiotherapy or surgery

Study type: Interventional

Funder types: Other

Identifiers

NCT05448547

GrandP

Details and patient eligibility

About

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.

Full 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.

Enrollment: 980 estimated patients

Sex: Male

Ages: 75+ years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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980 participants in 2 patient groups

immediate curative therapy

Experimental group

Description:

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.

Treatment:

Radiation: Radiotherapy or surgery

initial observation/ hormone therapy

Active Comparator group

Description:

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.

Treatment:

Drug: Hormone therapy

Other: initial observation