Neoadjuvant lutetium PSMA, the TIME and immune response in high-risk localized prostate cancer

Eapen, RS; Williams, SG; Macdonald, S; Keam, SP; Lawrentschuk, N; Au, L; Hofman, MS; Murphy, DG; Neeson, PJ

Author(s): Eapen, RS; Williams, SG; Macdonald, S; Keam, SP; Lawrentschuk, N; Au, L; Hofman, MS; Murphy, DG; Neeson, PJ;
Details: Publication Year 2024-11,Volume 21,Issue #11,Page 676-686
Journal Title: Nature Reviews Urology
Publication Type: Review
Abstract: High-risk localized prostate cancer remains a lethal disease with high rates of recurrence, metastases and death, despite attempts at curative local treatment including surgery. Disease recurrence is thought to be a result of failure of local control and occult micrometastases. Neoadjuvant strategies before surgery have been effective in many cancers, but, to date, none has worked in this setting for prostate cancer. Prostate-specific membrane antigen (PSMA)-based theranostics is an exciting and rapidly evolving field in prostate cancer. The novel intravenous radionuclide therapy, [(177)Lu]Lu-PSMA-617 (lutetium PSMA) has been shown to be effective in treating men with metastatic castration-resistant prostate cancer, targeting cells expressing PSMA throughout the body. When given in a neoadjuvant setting, lutetium PSMA might also improve long-term oncological outcomes in men with high-risk localized disease. A component of radiotherapy is potentially an immunogenic form of cancer cell death. Lutetium PSMA could cause cancer cell death, resulting in release of tumour antigens and induction of a tumour-specific systemic immune response. This targeted radioligand treatment has the potential to treat local and systemic tumour sites by directly targeting cells that express PSMA, but might also act indirectly via this systemic immune response. In selected patients, lutetium PSMA could potentially be combined with systemic immunotherapies to augment the antitumour T cell response, and this might produce long-lasting immunity in prostate cancer.
Publisher: Springer Nature
Keywords: Male; Humans; *Prostatic Neoplasms/therapy/immunology/pathology; *Lutetium/therapeutic use; *Neoadjuvant Therapy; Radioisotopes/therapeutic use; Glutamate Carboxypeptidase II/immunology; Dipeptides/therapeutic use; Antigens, Surface; Radiopharmaceuticals/therapeutic use; Heterocyclic Compounds, 1-Ring; Prostate-Specific Antigen
Department(s): Laboratory Research; Cancer Imaging; Surgical Oncology; Radiation Oncology; Medical Oncology
Publisher's Version: https://doi.org/10.1038/s41585-024-00913-8
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-11-28 06:25:30

Last Modified: 2024-11-28 06:29:09