In 2022, it is estimated that there will be approximately 270,000 new cases of prostate cancer and an estimated 34,500 people will die of this disease. Treatment of localized prostate cancer is often straightforward and can even include active surveillance or deferring initial treatment to avoid side effects of therapy. Conversely, managing patients with advanced prostate cancer is crucial for patient longevity and quality of life. The world of advanced prostate cancer has been transformed over the past decade with the introduction of a new class of oral agents–androgen receptor inhibitors. These drugs have markedly improved patients’ survival without any decrement in their quality of life. These oral therapies, while newish, have made a dramatic difference in patients with advanced prostate cancer. Several phase 3 clinical studies have demonstrated that adding oral oncolytics to patients’ treatment regimens delay the progression of castration resistance. Furthermore, these studies also show that up to 50% of patients still remain on therapy at five years, and these patients’ prostate cancer has still not progressed to castrate resistance, a poor prognostic event.
In addition to these important advances in the treatment of advanced prostate cancer, more therapeutic targets are being developed that will continue to alter the treatment and survival landscapes for patients. Notably, prostate specific membrane antigen (PSMA) is a protein specific to prostate cells that is preferentially expressed extracellularly on prostate cancer cells and intracellularly on normal or benign prostate tissue. Because of its specificity on the surface of prostate cancer cells, PSMA makes an ideal target for diagnostic and therapeutic purposes. In the second half of 2021, the FDA approved diagnostic PSMA PET scans, and these scans have rapidly become the standard diagnostic test for men with certain forms of prostate cancer.
Then, in March 2022, the FDA approved a novel therapeutic agent that specifically targets the PSMA protein. The ‘radioligand therapeutic agent’, Pluvicto, binds PSMA on the prostate cancer cell and then delivers a radioactive molecule directly to the cancer cell, resulting in death of the cancer cell with minimal radiation exposure to non-cancer cells. Pluvicto has initially been approved in men with more advanced forms of prostate cancer, providing a novel, well-tolerated treatment option for this group of men who previously had few choices. Further clinical trials are underway to evaluate the effectiveness of Pluvicto at an early point in the disease process. Finally, it is worth noting that many other PSMA-based therapies are in development that show great promise.
Over the past ten years, the treatment of advanced prostate cancer has transformed to the betterment of patients’ and their loved ones' lives. PSMA-targeting agents hold great promise and will surely have a significant role in the treatment paradigm of men with prostate cancer. Fortunately, therapeutic development has not and will not stop, and further pharmaceutical agents are being developed to continue the progress that has already witnessed, hopefully further transforming the survival of men with advanced prostate cancer.
