What occurs if PSA levels increase following radiation therapy or surgery for prostate cancer? This issue may eventually arise for up to one-third of men receiving treatment for the illness. Men experience what is known as a biochemical recurrence if imaging scans show no concurrent signs of malignancy. In this instance, PSA, the molecular marker, is indicating the existence of cancer cells that are still invisible to medical professionals.
Cancer that recurs biochemically is asymptomatic and may not show any symptoms for years. Men may have a growing PSA for the remainder of their life without ever seeing metastases.
The management of biochemical recurrence is now being challenged by new problems brought about by an ultra-sensitive scanning technology.
Test results influence treatment decisions
Prostate-specific membrane antigen (PSMA), a protein found on cancer cells, is illuminated by this scan. Small tumors in the body that are invisible with older, traditional imaging methods like magnetic resonance imaging or bone scans can be found using a PSMA scan.
For this illness, doctors have created a new term: (PSMA) + BCR.
Doctors rely treatment decisions on other indicators, like the rate at which PSA levels are rising, when a man has biochemical recurrence as defined by conventional definition and there is no indication of cancer on conventional imaging. Drugs that block testosterone, a hormone that promotes the growth and metastasis of prostate cancer, are typically administered once therapy is started. But because biochemical recurrence usually happens slowly, if at all, doctors may also postpone that treatment.
What happens if a man has both BCR and PSMA? After that, things become a little trickier. Many physicians are tempted to treat aggressively right away because the scan does reveal metastases, sometimes employing potent hormonal therapy combinations that have significant adverse effects.
A more sophisticated strategy is being demanded by some experts, though.
Dr. David Einstein, an assistant professor at Harvard Medical School and Disease Group Leader of the Genitourinary Medical Oncology Program at Beth Israel Deaconess Medical Center, says, “We have seen cases where patients have small cancerous lesions on a PSMA scan that do not necessarily grow.”
Weighing potential benefit against side effects
Some busy doctors may be surprised to learn that PSMA-detected disease can be postponed, as they often confuse it with metastatic cancer. However, Dr. Einstein advises physicians to keep in mind the knowledge already gained from researching patients who experience biochemical recurrence.
“For at least some PSMA-detected recurrences as well,” Dr. Einstein says, “biochemical recurrence can be associated with a decade or more of survival in cases where metastatic cancer that appears on conventional imaging is considered serious and aggressive (though progression varies from person to person).” In a publication published last year, Dr. Einstein and his colleagues stated that “many, if not most, men” with PSMA-detected recurrence face “no imminent threat of morbidity or fatality from their prostate cancer.”
Accelerated therapy for PSMA-detected recurrence may, in certain situations, only prolong a man’s life with harmful side effects for years, according to Dr. Einstein. Although treatment can slow progression and prevent subsequent PSA increases, there is currently little proof that treating biochemical recurrence actually extends survival.
The “natural history” of prostate tumors that recur and are only found by PSMA scans is now being investigated by researchers. This indicates that they are examining the disease’s propensity to spread, its timing, and its behavior over time, including how it reacts to therapy. Additionally, they are working on clinical studies for novel medicines that may be more beneficial than hormone therapy in the long run.
Informed decision-making
In the meantime, Dr. Einstein says, decisions on how to handle recurring cancer spotted by PSMA scanning should take other factors into account: They include:
- A man’s age and overall health. Some older men may die of other causes before recurring prostate cancer needs treatment. Pre-existing health problems such as heart disease or frailty may also affect his tolerance to therapy.
- If a man was initially treated for high-grade cancer with aggressive features, or if the cancer has returned quickly, then earlier treatment for PSMA-recurring cancer may be warranted.
- How fast is his PSA rising? Men whose PSA levels double the fastest are at the highest risk for developing metastases in the short term and “should at least consider early treatment,” Dr. Einstein says. Those with slow PSA doubling times can wait safely and have their disease monitored instead.
- How many tumors show up on a PSMA scan? If the tumors number fewer than five, then some doctors might treat them directly with radiation, although monitoring the cancer “is also reasonable, especially in men who do not have other high-risk features,” Dr. Einstein says. Some doctors might add a temporary course of hormonal therapy (drugs that block testosterone and its tumor-promoting effects). However, Dr. Einstein cautions that it still isn’t clear that adding hormonal therapy makes radiation work better in this setting.
- A man’s personal values and goals are also important, and should be carefully considered during conversations with his doctor.
“The advanced technology of PSMA scanning that detects very small deposits of cancer has raised important treatment questions that are now being actively studied,” says Dr. Marc B. Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and editor in chief of the Harvard Medical School Guide to Prostate Diseases. “Dr. Einstein’s leadership is providing much needed guidance on how to manage prostate cancer recurrence detected by PSMA scanning,” says Dr. Garnick. “Delaying or postponing treatments that would in the past have been given immediately is a strategy that is often embraced by our patients.”
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