Comparison of Intermittent Androgen Deprivation Therapy With or Without Irradiation Recovery in Prostate Cancer Patients

Screening procedures will be performed up to three months before starting IADT. After obtaining informed consent, patients will be randomly allocated to one of two groups:

Experimental group: IADT + IG-IMRT Control group: IADT

In both study arms, the first injection of IADT will be administered in hospital on the day of randomization. The overall duration of IADT will be six months.

In the experimental group, patients will receive radiotherapy three months after the first injection of IADT.

The overall duration of radiotherapy will be three months.

The overall duration of IADT will be six months. It will be administered three months, +/- 15 days prior to the first day of radiotherapy. At the completion of the six-month treatment period, a non-treatment interval will start if :

there is no evidence of clinical disease progression and the PSA level is ≤ 4.00 ng/ml If the PSA subsequently rises above 0.20 ng/ml and is confirmed by a second measurement at least three weeks later, PET/CT imaging will be repeated every 6 months until a clinical failure is detected or until the PSA rises above 4.00 ng/ml.

Inclusion criteria

• Histologically-proven prostate adenocarcinoma
• Age ≥ 18 years
• Performance Status 0-1
• Prior radical prostate treatment (surgery and/or radiotherapy)
• ≤ 5 metastatic pelvic lymph nodes detected by FCH-PET or PSMA-PET
• Upper limit of metastatic lymph nodes: aortic bifurcation
• If ADT has been previously administered to the patient, at least 12 months must have elapsed between the predicted duration of the last injection and inclusion of the patient in the study. For this category of patients, serum testosterone must be higher than 6 nmol/L (50 ng/L) prior to inclusion
• Biochemical relapse (according to the European Association of Urology guidelines) is defined by :

Following radical prostatectomy (RP), biochemical recurrence (BCR) is defined by two consecutive rising PSA values > 0.20 ng/ml After primary radiation therapy (RT), the Radiation Therapy Oncology Group (RTOG) and American Society for Radiation Oncology Phoenix Consensus Conference definition of PSA failure is any PSA increase > 2.00 ng/ml higher than the PSA nadir value, regardless of the serum concentration of the nadir.

• Having given written informed consent prior to any procedure related to the study.
• Patient is willing and able to comply with the protocol for the duration of the study including all scheduled treatment, visits and examinations.
• Patient has valid health insurance
• Subjects who have partners of childbearing potential must be willing to use a method of effective birth control during treatment and for 12 months following completion of treatment with ADT or IG-IMRT.

Exclusion criteria

• Bone or visceral metastases
• Para-aortic lymph node metastases (above the aortic bifurcation)
• Presence of more than five metastatic lymph nodes
• Evidence of local intra-prostatic relapse
• Evidence of prostate bed relapse in a previously irradiated region. Prostate bed relapses which have not been previously irradiated will not be excluded
• Evidence of metastasis at initial diagnosis
• Evidence of distant metastases beyond the pelvic lymph nodes
• Previous irradiation of pelvic lymph nodes
• Castration-resistant prostate cancer (CRPC) as defined by : a castrate serum testosterone < 6 nmol/L (50 ng/L)
• Contraindications to pelvic irradiation (e.g. chronic inflammatory bowel disease)
• Contraindications to ADT (known hypersensitivity to any of the study drugs or excipients)
• Severe uncontrolled hypertension defined as systolic BP ≥ 160 mmHg or diastolic BP ≥ 95 mmHg). Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive therapy
• Other malignancy treated within the last 5 years (except non-melanoma skin cancer)
• Patients with a biochemical relapse while on active treatment with LHRH-agonist, LHRH-antagonist, anti-androgen, maximal androgen blockade, or oestrogen
• Treatment during the past month with products known to influence PSA levels (such as finasteride)
• In case of previous prostate/prostate bed radiotherapy, PET-positive lymph nodes have to be located outside the previous irradiation field with a maximum of 20 Gy to the PET-positive lymph nodes region
• Patients already included in another therapeutic trial with an experimental drug or having been given an experimental drug within a period of 30 days
• Disorder precluding understanding of trial information or informed consent