Prostate cancer is the most common cancer in men. Its incidence is rising as the population ages. In the localized stage, the 5-year overall survival rate (OS) is 98%. Metastatic progression and resistance to castration have a negative impact on prognosis. Despite recent advances in management, the 5-year OS is around 30%. Therapeutic advances in this indication have been made mainly by the use of taxanes and second-generation hormone therapy. These treatments have improved OS and progression-free survival (PFS). They are now used as standard therapy.
More recently, the Phase III VISION trial confirmed the improvement in OS and radiological PFS achieved by treatment with the radioligand 177Lutetium-PSMA-617 (Lu-PSMA) in patients with advanced metastatic castration-resistant prostate cancer (mCRPC).
This treatment is currently available in early access in France. Despite encouraging results, 40% of patients will not respond to Lu-PSMA, and there are currently no validated predictive factors. Studies are currently on going, but the identification of biomarkers seems necessary to better stratify risk in these patients.
Numerous tissue prognostic tests based on molecular characteristics or cell proliferation are emerging with this in mind. At present, molecular profiling is not a routine technique for prostate cancer, as it is for other solid cancers. At an early stage, the Decipher® Genomic classification tool has shown prognostic utility independently of therapeutic and clinico-pathological data.
According to recent studies, methylome analysis would enable the subdivision of mCRPCs and could help identify new therapeutic targets.
In the metastatic phase, certain molecular abnormalities involving DNA repair genes are predictive of response to PARP inhibitors.
Molecular analysis (mutations, copy number alterations, gene expression, DNA methylation) could therefore be useful in optimizing the management of mCRPC patients treated with Lu-PSMA.
If reliable molecular abnormalities are identified on tissue, a diagnostic technique based on circulating tumor DNA (ctDNA) analysis will be useful in decision-making for these patients. A biological collection will therefore be created during the course of this study, with a view to using ctDNA analysis in subsequent research.
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
Continuation of second-generation hormone therapy Patient
Other cancer in the last 3 years likely to change life expectancy or interfere with the assessment of the disease
Protected adult
History of somatic or psychiatric illness/condition that may interfere with study objectives and evaluations
Single group
Blood samples
Biological/VaccineA total of 3 blood samples (2 tubes of 9mL each) are added. The first sample will be taken at the inclusion visit, the 2nd at the end of the 2nd treatment cycle and the last at the end of Lu-PSMA treatment.
Molecular abnormalities retained on primary tumor sample predicting response to Lu-PSMA in metastatic castration resistant prostate cancer patients assessed according to RECIST 1.1 and/or PCWG3 criteria
Biological interpretation and response to Lu-PSMA treatment on bone scan and CT scan according to RECIST 1.1 and/or PCWG3 criteria
Correlation between biomarker(s) (molecular abnormalities retained on primary tumor sample for the first outcome measure) and survival without radiological progression
Radiological progression free survival defined as the duration between the start date of treatment and the date of the first progression of the disease according to criteria RECIST V1.1 and criteria PCWG3; or the date of death whatever the cause.
Correlation between biomarker(s) (molecular abnormalities retained on primary tumor sample for the first outcome measure) and survival without biological progression
Biological progression free survival defined as the duration between the start date of treatment and the date of the first PSA progression
Correlation between biomarker(s) (molecular abnormalities retained on primary tumor sample for the first outcome measure) and survival without clinical progression
Clinical progression free survival, definieds as the duration between the treatment start date and the date of the first clinical progression
Correlation between biomarker(s) (molecular abnormalities retained on primary tumor sample for the first outcome measure) and overall survival
Overall survival definied as the time interval between the start date of treatment and the date of death whatever the cause
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Centre Jean Perrin
Lead sponsor
GIRCI Auvergne Rhone-Alpes
Collaborator
