Learn about PSMA and its value as a diagnostic and therapeutic target for metastatic castration-resistant prostate cancer (mCRPC).
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This site is created and funded by Novartis.
Early diagnosis is strongly linked to cancer survival for prostate cancer. Therefore, identifying reliable disease-specific biomarkers (any molecules that act as signals indicating the presence of a disease) is crucial to help improve patient survival.
There is a pressing demand for clinically relevant and targetable biomarkers that can help healthcare professionals to make informed decisions about the treatment of patients with prostate cancer.
Prostate-specific membrane antigen, or PSMA, is a biomarker used in the diagnosis of prostate cancer.
PSMA is naturally found in the prostate gland and other healthy tissues, however its expression is increased in prostate cancer lesions, making it a valuable imaging marker and therapy target for the disease.
High levels of PSMA have been directly linked with more aggressive prostate cancer:
5-year recurrence-free survival rates based on PSMA levels
Since PSMA is present in such a high percentage of prostate cancer patients, it is arising not only as an interesting diagnostic biomarker, but also as a therapeutic target. After successfully identifying PSMA-positive patients via a diagnostic imaging test, PSMA-targeted radioligand therapy has the potential to selectively target prostate cancer cells, with the goal of limiting damage to surrounding healthy cells.2
Patient preparation
For this method, a small radioactive molecule (“tracer”) is injected into a vein. The tracer targets and binds to the PSMA-positive prostate cancer cells. The whole body is then imaged in a PET/CT scanner that detects the areas in which the radioactive tracer has attached to the PSMA protein.3
What are the potential benefits?
Through this imaging technique it is possible to pinpoint tumor cells not only in the prostate but also throughout the pelvis and the body. It may enable health care professionals to visualize the distribution of the disease spread.4 5
What are the results used for?
PSMA PET/CT diagnosis can be used to tell whether prostate cancer has metastasized, or spread throughout the body, and, importantly, where it has spread, including bone, nodal, and visceral metastasis.
This information may allow healthcare professionals to tailor the clinical management to the individuals, including being able to select patients with PSMA-positive progressive metastatic castration-resistant prostate cancer who may be eligible for PSMA-targeted therapy.6
In addition to its diagnostic potential, PSMA has emerged as an attractive therapeutic target for radioligand therapy (RLT).
This highly-targeted treatment is comprised of two key components7a:
Radioligand therapy works to target PSMA-positive tumor cells through the following steps:7b
This leads to cell death of the cancer cell as well as its immediate neighboring cells, eliminating them with the goal of limiting the undesirable effects in healthy cells.
CT, computed tomography
DNA, deoxyribonucleic acid
mCRPC, metastatic castration-resistant prostate cancer
PET, positron emission tomography
PSMA, prostate-specific membrane antigen
RLT, radioligand therapy
1 Hupe MC, Philippi C, Roth D, et al. Expression of prostate-specific membrane antigen (PSMA) on biopsies is an independent risk stratifier of prostate cancer patients at time of initial diagnosis. Frontiers in Oncology. 2018;8:623. doi:https://doi.org/10.3389/fonc.2018.00623
2Sartor O, de Bono J, Chi KN, et al. Lutetium-177–PSMA-617 for metastatic castration-resistant prostate cancer. New England Journal of Medicine. 2021; 385(12):1091-1103. doi:10.1056/NEJMoa2107322
3Hofman MS, Lawrentschuk N, Francis RJ, et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study. Lancet. 2020;395(10231):1208-1216. doi:10.1016/S0140-6736(20)30314-7
4Calais J, Ceci F, Eiber M, et al.⠀18F-fluciclovine PET-CT and 68Ga-PSMA-11 PET-CT in patients with early biochemical recurrence after prostatectomy: a prospective, single-centre, single-arm, comparative imaging trial. Lancet Oncology. 2019;20(9):1286-1294. doi:10.1016/S1470-2045(19)30415-2
5Schwarzenboeck S, Rauscher I, Bluemel C, et al. PSMA ligands for PET imaging of prostate cancer. The Journal of Nuclear Medicine. 2017;58(10):1545-1552. doi:10.2967/jnumed.117.191031
6Fendler WP, Ferdinandus J, Czernin J, et al. Impact of 68Ga-PSMA-11 PET on the management of recurrent prostate cancer in a prospective single-arm clinical trial. The Journal of Nuclear Medicine. 2020;61(12):1793-1799. doi:10.2967/jnumed.120.242180
7a 7bPluvicto (lutetium Lu 177 vipivotide tetraxetan). Summary of product characteristics. Advanced Accelerator Applications (Italy) S.R. L. Accessed July 19, 2024. https://www.ema.europa.eu/en/documents/product-information/pluvicto-epar-product-information_en.pdf
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