Can men hold off on treating recurring prostate cancer?

What happens if PSA levels start rising after surgery or radiation for prostate cancer? Up to a third of men treated for the disease will eventually confront this problem. If there’s no accompanying evidence of cancer on imaging scans, then men have what’s called a biochemical recurrence. This means that PSA — the biochemical marker in this case — is flagging the presence of cancer cells that doctors are still unable to see.

Biochemically recurring cancer is asymptomatic, and it can take years for visible metastases to appear. Sometimes men live the rest of their lives with a rising PSA without ever developing metastases.

Now, an ultra-sensitive scanning technology is raising new questions about biochemical recurrence and how to manage it.

Test results influence treatment decisions
This scan works by illuminating a protein on cancer cells called prostate-specific membrane antigen (PSMA). A PSMA scan can reveal small tumors in the body that older, conventional imaging technologies, such as bone scans or magnetic resonance imaging, are unable to detect.

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Doctors have coined a new term for this condition: (PSMA) + BCR.

When a man has biochemical recurrence as it's traditionally defined, with no evidence of cancer on conventional imaging, doctors base treatment decisions on additional factors, such as how fast PSA levels are rising. If treatment is initiated, then a standard approach is to give drugs that block testosterone, a hormone that drives prostate cancer to grow and spread. But doctors might also delay that treatment, since biochemical recurrence tends to proceed slowly, if at all.

What if a man has (PSMA) + BCR? Then things get a bit more complicated. Since the scan does show metastases, many doctors are inclined to treat aggressively without delay, in some cases using powerful combinations of hormonal therapies that have considerable side effects.

However, some experts are calling for a more nuanced approach.

“We’ve encountered situations where patients have small cancerous lesions on a PSMA scan that don’t necessarily grow,” says 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.

Weighing potential benefit against side effects

That it’s possible to hold off on treating PSMA-detected disease may be surprising to some busy doctors who lump such cases together with metastatic cancer. But Dr. Einstein says doctors shouldn’t lose sight of what’s already known from studying patients with biochemical recurrence.

Where metastatic cancer that shows upon conventional imaging is considered serious and aggressive (though progression varies from person to person), biochemical recurrence can be associated with a decade or more of survival, and that’s likely true “for at least some PSMA-detected recurrences as well,” Dr. Einstein says. “Many, if not most, men” with PSMA-detected recurrence face “no imminent threat of morbidity or mortality from their prostate cancer,” Dr. Einstein and his colleagues wrote in a paper last year.

Dr. Einstein says accelerated treatments for PSMA-detected recurrence may in some cases do little more than add years of toxic side effects to a man’s life. There’s still no evidence that treating biochemical recurrence actually improves survival, though it can delay progression and keep further PSA increases in check.

Researchers are now studying the “natural history” of prostate cancers that reappear and are detected only with PSMA scans. This means they are looking at where and when the disease tends to spread and how it behaves over time, including responding to treatment. They are also in the process of developing clinical trials for new treatments that might have longer-lasting benefits than hormonal therapies.

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