A sickening feeling

Has this ever happened to you? You want to retrieve something small but important. Maybe it’s the key to your safe deposit box, or an heirloom gold watch chain from your great-grandfather. You go to the place you usually keep it, like a box in the back of a drawer, or a container on a closet shelf. But when you get there, it’s gone. Where could it be? It’s kind of a sickening feeling, but you tell yourself not to panic. You sift through memories. When did you last have it? Had you put it somewhere new? When no memory proves useful, you start ransacking other places. If only you had x-ray vision you could solve the mystery without a time-consuming search—but that’s wishful thinking. (With any luck, you finally find it—whew!—and only then do you recall having put it in a different place.)

In a very real sense, this “missing item” situation is similar to a mystery that has long plagued prostate cancer (PCa) patients and their doctors. When a patient is diagnosed with localized PCa, and goes through whew! — whole gland surgery or radiation, it’s called a definitive treatment with curative intent. In most cases, the doctor “got it all.” But sometimes the patient’s PSA begins to rise, raising suspicion that some cancer cells had already escaped and have spread. The thought of PCa activity hiding somewhere in your body causes a sickening feeling. Where could it be? Your doctor wants to do more tests, and encourages you not to panic.

PSMA-PET to the rescue

Until recently, doctors were limited to two tests, a bone scan and a conventional CT scan. However, neither could visually detect microscopic tumor spread. The longing to identify nearly microscopic tumor activity amounted to wishful thinking, but if left unmanaged it will inevitably take the patient’s body hostage. Therefore, patients were left with only one option: androgen deprivation therapy (“chemical castration”) to put the brakes on tumor activity. Even so, eventually their disease will outsmart the drugs and reveal itself. At that point, there may be little hope of living out one’s full lifespan.

Thankfully, we finally have a new way to detect very early, small metastasis, one that offers new hope for prolonging survival. We have posted numerous blogs on the miraculous power of PSMA-PET scan to detect tiny sites of early spread through the use of radioactive tracers. With this state-of-the-art imaging we can pinpoint PCa activity anywhere in the body, supplying crucial knowledge for planning treatment.

We found it! Now what?

Once we know the extent and location of a patient’s metastatic disease, treating it is not as simple as a one-size-fits-all therapy. That’s because one person’s PCa is not necessarily biologically identical to another’s. The differences occur at the level of a cell’s genetic variants (gene mutations). Many combinations of variants have been discovered, and they don’t all behave the same, nor respond the same way to treatments. Researchers have found that patients with metastatic PCa have more frequent characteristic genetic mutations than those with nonmetastatic PCa. Within the group of metastatic PCa patients, those whose tumor activity that responds to androgen deprivation, called castration sensitive PCa, have less mutational tumor burden than those with castration resistant PCa. The greater the mutational burden, the worse survival.^[i]

Thankfully, we’ve entered a revolutionary age with a new approach to personalizing treatment called theranostics. We now have a wide array of chemotherapies, immunotherapies, and PSMA-targeted therapies that can be used separately or in combination. Before deciding on the best strategy tailored to a given patient, however, experts recommend genetic testing for patients with metastatic PCa, especially castration resistant disease. Certain mutations “…have prognostic value and become increasingly relevant as predictive biomarkers for therapies…” meaning biological information used to guide treatment decisions.^[ii]

To sum up, if a PCa patient’s PSA begins to rise after a definitive whole gland treatment, PSMA-PET scans are the best fulfillment of the wish to pinpoint any cancer spread anywhere in the body, as early as possible. Once the location(s) have been identified, the next step toward developing a treatment plan should be genetic testing. Patients with metastatic PCa have every reason to be optimistic, even confident, that when the location and nature of their cancer have been discovered, the best treatment match will be found.

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] Al-Toubat M, Serrano S, Elshafei A, Koul K, Feibus AH, Balaji KC. Metastatic prostate cancer is associated with distinct higher frequency of genetic mutations at diagnosis. Urol Oncol. 2023 Nov;41(11):455.e7-455.e15.
[ii] Barata PC, Assayag J, Li B, Siu G, Niyazov A. Genetic Testing in Men With Metastatic Castration-Resistant Prostate Cancer. JAMA Oncol. Published online May 02, 2024.