When you’re in a hurry to get somewhere, you’re likely to take the path of least resistance, the route you’re most familiar with. It’s easy because you know it well. However, when it comes to knowing whether or not you have prostate cancer (PCa), the most familiar route is not always the best way to get to your destination.

Until recently, the most familiar diagnostic pathway went from a suspicious PSA test (and perhaps also a digital rectal exam or DRE) directly to a prostate biopsy. Sure, it was the fastest route because a urologist could perform a 12-14 needle biopsy guided by transrectal ultrasound (TRUS) right in his office. However, TRUS biopsies have a substantial margin of error—either underestimating clinically significant PCa, or overestimating insignificant PCa—and side effect risks like pain, infection, and even sexual dysfunction.

Nowadays, when there’s a rush to biopsy, two new clinical technologies give patients good reason to say “Not so fast, doc.” Of course, you don’t want to drag your feet getting a diagnosis—but you need more information so you can knowledgeably apply the brakes before you hop up on the biopsy table. One of the revolutionary technologies is already familiar to patients everywhere. It’s multiparametric MRI (mpMRI). Unlike ultrasound, mpMRI done by an expert provides a 3D high resolution portrait of suspicious lesions, including important clues regarding whether or not it’s clinically significant. Many studies show that mpMRI before biopsy can determine if needles samples are necessary.

The other revolutionary development is less well known to patients; even some doctors have not yet caught on to it! It’s the discovery of unbelievably tiny packets of information that cells use to communicate with other cells throughout the body. They are called extracellular vesicles (EVs). Almost all cells, including cancer cells, produce these nano-sized “messengers” that contain instructional “cargo” in the form of proteins and molecules like mRNA (messenger RNA). They also carry markers that act as ID tags regarding the EV’s “parent” cell. When released by a parent cell, EVs circulate in bodily fluids (e.g. blood, urine). When a cell elsewhere in the body intercepts an EV and allows it to enter, the receiver “opens” the envelope to “read” its contents. These contents instruct the receiver to behave in certain ways. In fact, it appears that not only can cargo from cancer cell EVs instruct other cancer cells, cancer EVs may actually transform normal cells into cancerous cells! Thus, they impact cancer progression, including PCa.

“These findings, combined with those demonstrating that the amounts and contents of EVs produced by cancer cells can vary depending on their cell of origin, stage of development, or response to therapies, have raised the exciting possibility that EVs can be used for diagnostic purposes,” write Chang, et al. (2021).^[i] A subset of EVs called exosomes are a new secret ingredient that can help determine if a biopsy is needed. PCa exosomes can be detected in a simple urine test that does not require a DRE. Since they can be isolated in a lab, they can be analyzed for genomic markers that are elevated in high grade PCa. One such test is the ExoDx Prostate Test, and in 2019 the FDA granted it Breakthrough Designation for its potential role as a liquid biopsy before needle biopsy, an idea that undoubtedly warms the hearts of men with suspicious PSA test results who want to take extra precautions before agreeing to a biopsy.

Even more exciting is the combined information from mpMRI and EVs. At the January, 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO-GU), a group led by Mayo Clinic urologist Dr. Cameron Britton presented their study involving 175 patients who had mpMRI, blood tests (for PSA and PCa EVs) and a prostate biopsy.^[ii] Their study showed that evaluating patients before biopsy using combined mpMRI, blood-derived EVs, and PSA variants “demonstrated better predictive ability for [clinically significant PCa] on biopsy compared to imaging or serum testing alone.”

EVs and their subset exosomes are the latest secret sauce in the recipe for PCa diagnosis. It’s amazing to think that back in the 1980s, when they were first identified as entities emitted by cells, biologists thought they were simply garbage bags ejecting trash from the interior of cells. It’s only in the past two decades that they have begun to be understood as a means by which information and instructions are exchanged among virtually all cells. That’s why EVs/exosomes can supplement mpMRI if needed to help determine biopsy necessity.

Remember: if a biopsy is warranted, the most accurate diagnosis obtained with or without EV analysis, using the least number of needles, is a real-time in-bore targeted biopsy performed on a powerful 3T magnet. Dr. Dan Sperling is a leading specialist in MRI-guided targeted biopsy. Contact us for more information.

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] Chang WH, Cerione RA, Antonyak MA. Extracellular Vesicles and Their Roles in Cancer Progression. Methods Mol Biol. 2021;2174:143-170.
[ii] Britton CJ, Andrews JR, Arafa A, et al. Prostate extracellular vesicles and prediction of clinically significant prostate
cancer: a prospective single-institution pilot study. Poster presented at the 2024 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium (ASCO-GU, San Francisco, Calif.