After surgery or radiation for prostate cancer, many men face a common concern: a rising PSA level. This occurs in up to one-third of those treated for the disease. When imaging scans show no visible cancer, this situation is termed a biochemical recurrence. Here, PSA—a biochemical marker—signals the presence of cancer cells that remain undetectable by conventional methods. Biochemical recurrence typically causes no symptoms, and it can take years for metastases to become apparent. In some cases, men live out their lives with increasing PSA levels without ever developing visible spread of the disease.
Now, a highly sensitive scanning technology is prompting fresh discussions about how to manage biochemical recurrence. This scan targets a protein on cancer cells known as prostate-specific membrane antigen (PSMA). By illuminating PSMA, the scan can reveal small tumors that older imaging techniques like bone scans or magnetic resonance imaging might miss. Doctors have introduced a new term for this condition: PSMA-positive biochemical recurrence, or (PSMA) + BCR.
When biochemical recurrence is identified without evidence on conventional scans, treatment decisions often hinge on additional factors, such as the rate at which PSA levels are climbing. If intervention is chosen, a standard approach involves drugs that block testosterone, a hormone that fuels prostate cancer growth and spread. However, doctors may also opt to delay treatment, as biochemical recurrence often progresses slowly or not at all.
The scenario becomes more complex with (PSMA) + BCR. Since the scan does show metastases, many physicians lean toward aggressive treatment without delay. This might include potent combinations of hormonal therapies, which can carry significant side effects. Yet, some experts advocate for a more measured strategy.
“We’ve encountered situations where patients have small cancerous lesions on a PSMA scan that don’t necessarily grow,” notes Dr. David Einstein, Disease Group Leader of the Genitourinary Medical Oncology Program at Beth Israel Deaconess Medical Center and assistant professor at Harvard Medical School.
Balancing potential benefits against side effects is crucial. It might come as a surprise to some clinicians that delaying treatment for PSMA-detected disease could be an option, especially if they group such cases with metastatic cancer. But Dr. Einstein emphasizes that insights from studying biochemical recurrence should not be overlooked.
While metastatic cancer visible on conventional imaging is generally considered serious and aggressive—though progression varies individually—biochemical recurrence can be associated with a decade or more of survival. This likely holds true “for at least some PSMA-detected recurrences as well,” Dr. Einstein explains.
In a paper published last year, Dr. Einstein and colleagues wrote that “many, if not most, men” with PSMA-detected recurrence face “no imminent threat of morbidity or mortality from their prostate cancer.” He points out that accelerated treatments for these cases may, in some instances, primarily add years of toxic side effects to a patient’s life.
Currently, there is no evidence that treating biochemical recurrence actually improves survival, though it can delay progression and help control further PSA increases. Researchers are now investigating the “natural history” of prostate cancers that reappear and are detected only with PSMA scans. This involves studying where and when the disease tends to spread, how it behaves over time, and its response to treatment. Additionally, clinical trials are underway to develop new therapies that may offer longer-lasting benefits than hormonal treatments.
In the interim, Dr. Einstein suggests that decisions on managing recurring cancer identified by PSMA scanning should consider several key factors. These include a man’s age and overall health. Older individuals might die from other causes before recurring prostate cancer requires treatment. Pre-existing conditions like heart disease or frailty can also affect tolerance to therapy.
If a man was initially treated for high-grade cancer with aggressive features, or if the cancer has returned quickly, earlier intervention for PSMA-detected recurrence may be justified. The rate of PSA increase is another critical element. Men with the fastest PSA doubling times are at the highest risk for developing metastases in the short term and “should at least consider early treatment,” Dr. Einstein advises. Those with slower doubling times can often wait safely and opt for monitoring instead.
The number of tumors visible on a PSMA scan also plays a role. If fewer than five tumors are detected, some doctors might treat them directly with radiation. However, monitoring the cancer “is also reasonable, especially in men who do not have other high-risk features,” Dr. Einstein says. In some cases, a temporary course of hormonal therapy—drugs that block testosterone and its tumor-promoting effects—might be added. Yet, Dr. Einstein cautions that it remains unclear whether combining hormonal therapy with radiation enhances effectiveness in this context.
A man’s personal values and goals are equally important and should be thoroughly discussed 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,” Dr. Garnick adds. “Delaying or postponing treatments that would in the past have been given immediately is a strategy that is often embraced by our patients.”
