177Lu-PSMA as a Systemic Adjuvant Treatment in Patients With High and Very High Risk Prostate Cancer

The intervention will consist of a single administration of 177Lu-PSMA in the research arm. Both the study and control groups will receive standard hormone therapy.

The study population includes 200 adult men with high-risk or very high-risk prostate cancer, with no signs of cancer dissemination in radiological examinations after completion of radiotherapy and continued hormone therapy

Participation time in the Study:

intervention phase - 1 day; observation phase - 5 years

• Lutetium (177Lu) vipivotide tetraxetan (Drug), also known as Pluvicto: The intervention will consist of a single administration of 7,4 GBq of lutetium (177Lu) vipivotide tetraxetan

Primary outcomes

• Treatment effectiveness [2 and 5 years after end of treatment]: Assessment of treatment failure - the assesment of biochemical progression ratio, defined as a rise of PSA by 2 ng/mL or more above the nadir, proven by a consecutive examination performed at least 4 weeks later

Secondary outcomes

• Biochemical progression-free survival [During the intervention and follow up period (assessed up to 5 years)]: Comparative assessment of biochemical progression-free survival time defined as an increase in tPSA (prostate specific antigen) in the blood above the nadir (the lowest PSA value after completion of treatment) by 2 ng/mL or more, confirmed in the next test performed no earlier than after 4 weeks
• Radiological progression-free survival [During the intervention and follow up period (assessed up to 5 years)]: Comparative assessment of radiological progression-free survival defined according to PCWG3 criteria
• Time until the next therapeutic intervention [During the intervention and follow up period (assessed up to 5 years)]: Comparative assessment of the time until the next therapeutic intervention
• Incidence of Treatment-Emergent Adverse Events according to CTCAE v 5.0 [During the intervention and follow up period (assessed up to 5 years)]: Comparative assessment of safety and tolerability of treatment according to CTCAE v 5.0
• Quliaty of life [During the intervention and follow up period (assessed up to 5 years)]: Comparison of EORTC QLQ-PR25 quality of life indicators between study groups

Sex: Male, ages: 18 Years to any

Inclusion Criteria:

* Giving a written informed consent
* Histopathologically confirmed high or very high risk prostate cancer
* Completion of radical locoregional treatment
* Completion of locoregional treatment within 3 months before inclusion to the study
* ECOG performance status 0 to 2
* Age over 18 years
* Within 28 days before entering the study, there were no signs of cancer dissemination documented in radiological tests
* Castrate testosterone level (testosteron < 50 ng/dL lub 1,7 nmol/L)
* Patients with adequate function of main organs:

  * bone marrow:

    * neutrophils > 1500x10\^9/L;
    * thrombocytes > 100,000x10\^9/L;
    * hemoglobin > 9 g/dL
  * liver:

    * bilirubin < 2xULN (upper limit of normal) in patients with Gilbert's syndrome < 5xULN;
    * aminotransferase < 3xULN
  * kidneys:

    * eGFR > 50 ml/min
    * albumin >2.5 mg/ml
* For men of reproductive age: the need to use double barrier contraception

Exclusion Criteria:

* The presence of distant metastases confirmed by radiological examination
* Absence of approval to use effective contraception method
* Absence of Patient's consent to participate in the Study
* Urinary tract obstruction or/and hydronephrosis.
* Concurrent anticancer treatment.