Radioligand Therapy of Patients with Metastatic Castrate-Resistant Prostate Cancer

Prostate cancer is a serious social and medical problem all over the world. It ranks fifth in the total structure of cancer morbidity and second in the structure of morbidity and mortality of men with neoplasms and takes the lead in growth rates. Androgen-deprivation therapy is insufficiently effective for the treatment of patients with metastatic castrate-resistant prostate cancer (mCRPC). This makes it relevant to develop novel methods for treating patients with this disease. Radioligand therapy (RLT) for metastatic castrate-resistant prostate cancer using low molecular ligands with high affinity to prostate specific membrane antigen (PSMA) labeled with beta- and alpha-emitting isotopes is currently under rapid development. One of the most promising radionuclide medicines is the Lu-177-PSMA-617 radiopharmaceutical based on the PSMA-617 ligand. The decay of Lu-177 results in the emission of both beta particles and gamma-rays. Therefore, it may also be used for therapy and SPECT diagnostics of malignancies. Lu-177-PSMA-617 is currently at different phases of clinical trials in many countries; however, it has not yet been registered. Most medical centers use the standard activity of 6 or 7.5 GBq per cycle (six or eight weeks between cycles), which causes less than 10% of serious adverse events (mainly hematological ones). Grade 3 anemia and thrombocytopenia develop in about 10% of patients, grade 1-2 dry mouth in 66%, and transient nausea of the 1st or 2nd degree in 48% of patients. The positive effect of RLT has been recorded: pain relief in 33-70% of patients, improvement of life quality in 60%, and an increase in Karnofsky's status in 74%. A biochemical response after RLT has been detected in more than half of the patients; among them, the PSA decreased by more than 50% in 45% of cases; in addition, this was observed after the first course in most cases; according to the data based on imaging methods, a partial response was recorded in more than a third of patients.