Originally published 6/10/2022
In March 2022, the FDA approved 177Lu-PSMA-617 (brand name Pluvicto) for the treatment of castration resistant metastatic prostate cancer (mCRPC) when androgen deprivation and chemotherapy are no longer effective.
It was shown to add months to overall survival. By July 2023, it was hailed as “one of the new frontline treatment options” for mCRPC by Patell, et al. (2023).[i] The authors noted, “While this treatment is tolerable and effective, biomarkers are necessary to determine which patients will benefit.”
Now, a year later, a new biomarker analysis has been developed to monitor how well Pluvicto other novel mCRPC treatments are working, and to provide cancer-specific genomic information to help develop new treatments.
A Belgian research team has published their study[ii] on exosomes, which are essentially tiny vesicles (packets of cargo) that cells manufacture to communicate with each other. Virtually all healthy cells can produce these nanoparticles and release them into circulation, but so can cancer cells. The cargo they contain can influence the behavior of any cell that receives them.
As a July 10, 2024 news story reports, “These vesicles, when produced by tumor cells, play a crucial role in cancer progression and metastasis. However, their potential as a source of clinically relevant DNA and RNA biomarkers has been largely unexplored until now.”
Since the exosomes are marked with molecular tags, analyzing them identifies their parent cells (in this case, mCRPC tumor cells) and decodes their contents. The story adds that by capturing them in patient blood samples, they have the potential to “predict treatment response, identify mechanisms of drug resistance, and provide new avenues for studying cancer through non-invasive methods.”
The results of a clinical trial with 53 mCRPC patients revealed patient-specific genomic details of their disease, offering a promising way to study response and resistance to Pluvicto and other new treatments for mCRPC.
The word cure seems to be disappearing from talk about cancer. These days, doctors are more likely to talk about cancer control, rather than cure. This is partly because cancers that used to be a death sentence are now seen as a chronic disease that patients can live with for years, thanks to recent target and-manage therapies that control ongoing problems as they arise.
However, when prostate cancer (PCa) is diagnosed and treated early, 95% of patients appear to be “cured”. This means there are no future signs that their disease is back. They go about their lives, and ultimately die from other causes.
Tragically, some men are diagnosed when their cancer has already begun to spread (metastasize) to other parts of the body. While there is still no cure for metastatic prostate cancer (mPCa), there is a new method for destroying PCa that has colonized bone and/or other organ tissues. It is a hope-filled, exciting new treatment approach called theranostics, a term that’s a blend of therapy and diagnostics.
The new treatment, called 177Lu-PSMA-617, is described in a Memorial Sloan Kettering newsletter as using “…a molecule that selectively seeks out and attaches to a specific protein on the cancer cell surface called PSMA (prostate-specific membrane antigen). The technology delivers radiation that damages DNA and destroys the cancer cell.”
This approach evolved from PSMA-PET scanning to detect prostate cancer recurrence, which is often metastatic. Since PCa cells have 100-1000 times more PSMA on their surface than normal cells, tiny radiotracer molecules stick to them like glue, and light up on PET scans. This reveals the location of even very small sites of PCa tumors. So, it was logical that if imaging could take advantage of PSMA to target cell locations, the next step would be harnessing this technology to deliver a lethal blow to the cells themselves.
The radiopharmaceutical manufacturer of 177Lu-PSMA-617, Novartis, states, “After administration into the bloodstream, 177Lu-PSMA-617 binds to prostate cancer cells that express PSMA, a transmembrane protein, with high tumor-to-normal tissue uptake.. Once bound, emissions from the radioisotope damage tumor cells, disrupting their ability to replicate and/or triggering cell death.” A clinical trial called VISION, a phase 3 study, enrolled 381 patients with PSMA-detectable mPCa that no longer responded to androgen deprivation therapy. The investigators found, “The PSMA-targeted radioligand 177Lu-PSMA-617 prolonged overall survival and delayed imaging-based progression when added to standard care in patients with PSMA-expressing metastatic castration-resistant prostate cancer.”[iii]
177Lu-PSMA-617 is not yet a complete cure, but it offers longer life. With the abundance of research occurring, a definitive cure may be just around the corner. It’s worth it to extend a man’s lifetime in hopes that that corner is turned as soon as possible.
NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.
References
[i] Patell K, Kurian M, Garcia JA, Mendiratta P et al. Lutetium-177 PSMA for the treatment of metastatic castrate resistant prostate cancer: a systematic review. Expert Rev Anticancer Ther. 2023 Jul;23(7):731-744.
[ii] Casanova-Salas I, Aguilar D, Cordoba-Terreros S, Agundez L, Brandariz J et al. Circulating tumor extracellular vesicles to monitor metastatic prostate cancer genomics and transcriptomic evolution. Cancer Cell. 2024 Jul 8;42(7):1301-1312.e7.
[iii] Sartor O, de Bono J, Chi KN, Fizazi K et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021 Sep 16;385(12):1091-1103.
About Dr. Dan Sperling
Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Prostate Center.
