The aim is to investigate whether the addition of short-term androgen deprivation therapy (ADT) during 1 month or short-term ADT during 6 months together with an androgen receptor targeted therapy (ARTA) to metastasis-directed therapy (MDT) significantly prolongs poly-metastatic free survival (PMFS) and/or metastatic castration-refractory prostate cancer free survival (mCRPC-FS) in patients with oligorecurrent hormone sensitive prostate cancer.
Metastasis-directed therapy (MDT) has broadened the therapeutic window in patients presenting with oligorecurrent prostate cancer as it postpones the initiation of palliative androgen deprivation therapy (pADT) and its substantial side-effects for several years. Also from a biological point of view, this might be beneficial as the (early) use of ADT promotes the development of the lethal castrate-resistant state, whereby metastatic progression is driven by androgen-independent pathways. Metastasis-directed therapy with stereotactic body radiotherapy (SBRT) or surgery has shown to be able to eradicate metastases with a significant advantage concerning the pADT-free survival compared to active surveillance. And the combination of SBRT with palliative systemic treatment significantly improved overall survival (OS) when compared tot systemic treatment alone. One of the largest retrospective analyses (191 patients) on MDT for oligorecurrent prostate cancer has been conducted previously at UZ Leuven (doi: 10.3390/cancers12082271). Estimated median pADT-free survival was 66 months and estimated median mCRPC-free survival was not reached, but 83% of patients were still free of mCRPC at 10 years. The addition of ADT to primary radiotherapy for intermediate of high risk prostate cancer or to salvage radiotherapy has shown to improve overall survival. Within the context of SBRT for oligorecurrent disease it is not yet known whether the addition of a certain period of ADT prolongs CRPC-free survival and if so, what should be the optimal duration of this ADT administration. Moreover, the addition of an androgen receptor targeted agent (ARTA) to ADT in men with metastatic hormone sensitive prostate cancer and a treated primary tumor resulted in significantly improved clinical outcomes, also in low-volume metastatic disease. In this clinical trial the aim is to investigate whether the addition of short-term ADT during 1 month or short-term ADT during 6 months together with an ARTA to MDT significantly prolongs poly-metastatic free survival (PMFS) and/or metastatic castration-refractory prostate cancer free survival (mCRPC-FS) in patients with oligorecurrent hormone sensitive prostate cancer.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
873
Metastasis-directed therapay (surgery and/or radiotherapy) as treatment for oligorecurrent lesions
Arm B: gosereline 3.6 mg sc, leuproreline 7.5 mg sc, triptoreline 3.75 mg im Arm C: gosereline 3.6 mg sc 1x/month or gosereline 10.8 mg sc or leuproreline 7.5 mg sc 1x/month or leuproreline 45 mg sc or triptoreline 3.75 mg im 1x/month or triptoreline 11.5 mg im 1x/3months or triptoreline 22.5 mg im
Enzalutamide
University Hospitals Leuven
Leuven, Belgium
RECRUITINGPoly-metastatic free survival (PMFS)
from the last day of MDT until the first day of poly-progression which is defined as the detection \> 5 new lesions at PSMA PET-CT or PSMA PET-MRI (+/- combined with MRI if needed to improve diagnostic accuracy). In case of poly-progression, pADT will be considered the standard-of-care. Other indications to start pADT are local progression of an irradiated site and/or or clinical symptoms caused by local progression. In all cases, the initiation of pADT will only be carried out after approval of the multidisciplinary tumor board. Any decision to start with pADT will be reported with date and specific reason. If recurrence occurs in 5 lesions or less a new MDT is proposed if technically feasible.
Time frame: up to 5 years after MDT
Metastatic castration-refractory prostate cancer free survival (mCRPC-FS)
mCRPC-FS will be calculated from the last day of MDT until the first day of diagnosis of castration-resistant prostate cancer (CRPC). CRPC is defined according to the contemporary EAU-guidelines as the time to biochemical and/or clinical progression at castrate testosterone levels (\< 50 ng/dl). Biochemical progression is defined as three consecutive PSA rises (1 week interval), of which at least 2 rises with a PSA level of \> 2 ng/ml and a rise of 50% above the nadir PSA level
Time frame: up to 5 years after MDT
Biochemical progression-free survival (bPFS)
bPFS will be calculated from the last day of MDT until the first day of biochemical relapse (BcR). BcR is defined as three consecutive PSA rises (1 week interval), of which at least 2 rises with a PSA level of \> 2 ng/ml and a rise of 50% above the nadir PSA level.
Time frame: up to 5 years after MDT
Clinical progression free survival (cPFS)
cPFS will be calculated from the last day of MDT until the first day of progression (local, nodal or metastatic) on PSMA PET-CT or PSMA PET-MRI. Imaging is performed in case of BcR, defined as above. Progression on PSMA PET-CT or PSMA PET-MRI will be defined as in the consensus statements on PSMA PET-CT or PSMA PET-MRI response assessment criteria in prostate cancer: * the appearance of 2 or more new PSMA PET-CT or PSMA PET-MRI lesions or increase of uptake or tumor PET volume of at least 30%. * OR the appearance of 1 new lesion with a high suspicion on PSMA PET-CT or PSMA PET-MRI
Time frame: up to 5 years after MDT
Cancer Specific Survival (CSS)
Cancer specific survival (CSS) will be calculated from last day of treatment until PCa death.
Time frame: up to 10 years after MDT
Overall Survival (OS)
Overall survival (OS) will be calculated from last day of treatment until death from any cause.
Time frame: up to 10 years after MDT
Acute and late toxicity scoring
Acute and late toxicity as a result of radiotherapy will be scores using the Common Toxicity Criteria Version 5.0 (30).
Time frame: up to 5 years after MDT
Quality of life (QOL)
Quality of life scoring using the EORTC QLQ-C30 supplement with QLQ-PR25. We will assess the quality-of-life-years with the EuroQOL classification system (EQ-5D-5L). Assessments are planned at baseline, last day of treatment, and during follow-up consultation at month M1, M3, M6, M12 and M24
Time frame: up to 5 years after MDT
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