Intrinsic Validity of Molecular Marker(s) Detection on Tissular Tumoral DNA to Predict the Efficacy of 177Lutetium-PSMA-617 (Lu-PSMA) Treatment for Castration-resistant Metastatic Prostate Cancer

Prior treatment

• Continuation of second-generation hormone therapy Patient
• Dilation of pyelocalicial cavities not previously supported
• Concurrent participation in a therapeutic trial and administration of any investigational agent within 28 days of inclusion
• Previous treatment with any of the following in the 6 months prior to inclusion : Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-cyclic irradiation
• Previous treatment with radioligands targeting PSMA

Other illness

• Other cancer in the last 3 years likely to change life expectancy or interfere with the assessment of the disease
• History of somatic or psychiatric illness/condition that may interfere with study objectives and evaluations
• Metastatic tumor tissue as the only material available for prostate cancer diagnosis
• Known hypersensitivity to one of the study treatments or its excipients or similar class drugs

Other

• Protected adult
• Patient unable to understand and comply with study instructions and requirements
• ECOG \> 2
• Obstruction of bladder discharge or uncontrollable and simultaneous urinary incontinence
• Symptomatic spinal cord compression or clinical or radiological findings indicating imminent spinal cord compression
• Fractured risk of bone damage
• Active and symptomatic brain injury
• Transfusion or use of bone marrow stimulating agents for the sole purpose of making a participant eligible for inclusion in the study

• Male \>18 years of age
• ECOG ≤ 2
• Patient with histologically confirmed of metastatic castration resistant prostatic adenocarcinoma and with tumor biological material available (prostatic biopsies or prostatectomy)
• Patient who received at least one taxane line and a second generation hormone therapy line
• Patient receiving androgen deprivation therapy with serum testosterone \< 50 ng/dL or \< 1.7 nmol/L or having undergone surgical castration
• Progressive mCRPC based based on at least 1 of the following criteria :
  • Serum or plasma PSA progression defined as 2 consecutive increases in PSA measured at least 1 week prior. The minimal start value is 2.0 ng/mL ; 1,0 ng/mL is the minimal start value if confirmed increase in PSA is the only indication of progress
  • Soft-tissue progression by RECIST 1.1 criteria
  • Progression of bone disease : two new lesions ; only the positivity of bone scan defines metastatic bone disease, according to PCWG3 criteria.
• Patients with at least one metastasis, bone and/or soft tissue and/or visceral, documented by the following methods in the 43 days prior to inclusion :
  • Bone metastasis (regardless of location) highlighted by bone scan AND/OR
  • Lymph nodes metastasis, regardless of size and location; if the metastasis are only lymph nodes, the short axis of at least one node should be at least 15 mm AND outside the pelvis ; AND/OR
  • Visceral metastasis, regardless of size and location; a history of visceral metastasis at any time prior to randomization should be encoded as the presence of visceral metastasis at baseline (i.e., a patient with visceral metastasis prior ADT introduction which are disappeared at baseline will be counted as having visceral metastasis and will be considered to have a high tumor volume during stratification)
• Patient with Lu-PSMA treatment indication, confirmed by PET 68Ga-PSMA-11. Eligibility for 68Ga-PSMA-11 PET is defined as:
  • At least one lesion with a binding intensity greater than that of the liver parenchyma (definition of positivity),
  • All lymph node lesions larger than 25 mm in the short axis must be positive on PSMA PET
  • All bone metastases with a soft tissue component ≥ 10 mm in the largest diameter must be positive on PSMA-PET
  • All solid organ metastases (e.g., lung, liver, adrenal glands, etc.) ≥ 10 mm in the largest diameter must be positive on PSMA-PET.
• Adequate organ function :
  • Bone marrow reserve :
  • Absolute neutrophil count ≥ 1.5 x 10\^9/L
  • Platelets ≥ 100 x 10\^9/L.
  • Hemoglobin ≥ 9 g/dL
  • Hepatic function :
  • Total bilirubin ≤ 2 x the upper limit of normal (ULN). For participants with known Gilbert's Syndrome ≤ 3 x ULN is permitted.
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x ULN OR ≤ 5.0 x ULN for patients with liver metastases.
  • Albumin \> 2.5 g/dL
  • Renal function : Glomerular Filtration Rate (GFR) ≥ 50 mL/min/1.73m2 according to MDRD equation.
• Obtaining the patient's free and informed consent
• Social security scheme or beneficiary.