Delaying treatment for PSA-only relapse poses won’t hurt survival in some men

By Charlie Schmidt

After surgery or radiation therapy for prostate cancer, some men get an unwelcome surprise—a sudden spike in the level of prostate-specific antigen (PSA), a protein made only by prostate cells. It may be an entirely harmless signal, or it may mean the cancer hasn’t been entirely eradicated and is beginning to regrow. Some men want to start hormone treatment immediately, others are okay waiting for other signs like the appearance of prostate cancer symptoms. A study presented this week at the American Society of Clinical Oncology’s (ASCO) annual meeting in Chicago indicates that waiting for up to two years poses little risk to survival.

Since PSA is made only by prostate cells, there shouldn’t be any in the bloodstream after a radical prostatectomy, the operation done to remove a cancerous prostate gland. There may be a small amount in the bloodstream after radiation treatment, which can leave small amounts of the prostate intact. When a man’s PSA level rises above a predefined threshold but he does not have any symptoms or other visible evidence of cancer, he is said to be experiencing a PSA-only relapse, sometimes called a biochemical relapse. Doctors have traditionally treated these men with hormone therapy to deprive prostate cancer cells of growth-fueling testosterone. The downside is that hormone therapy has significant side effects, including difficulty getting or keeping an erection, hot flashes, fatigue, or breast tenderness or pain.

Since the reason for a post-treatment PSA spike isn’t always known, and since hormone therapy has unwanted side effects, waiting before starting may make sense for some men. There currently aren’t any widely accepted guidelines for when to start hormone therapy among the 60,000 U.S. men who have PSA-only relapses each year.

Researchers from the Harvard School of Public Health and the University of California, San Francisco studied data from about 2,000 men with PSA-only relapse who were tracked in a national prostate cancer registry. Some of the men chose to start hormone therapy within three months of learning about a PSA-only relapse, while others started at least two years later or when evidence of cancer began to appear. At the cancer meeting, principal investigator Xabier Garcia-De-Albeniz, a research associate at the Harvard School of Public Health, reported no difference in five-year and 10-year overall survival rates between men waited and those who began hormone therapy immediately.

The main shortcoming of the study is that men weren’t randomized to either approach. That means differences between the two groups could have influenced the study results, although Garcia-Albinez said efforts were made to control for that possibility.

Dr. Clifford Hudis, the president of ASCO and chief of the breast cancer service at Memorial Sloan Kettering Cancer Center in New York, said the study provides much-needed evidence that delaying treatment can be safe. He said that men with PSA-only relapse and their doctors should take these results into consideration when deciding whether, or when, to begin hormone therapy.

The results may not apply to all men with PSA-only relapse, but “they do offer some encouraging news to the majority of men who experience it,” added Dr. Marc B. Garnick, a clinical professor of medicine at Harvard Medical School, an oncologist at Beth Israel Deaconess Medical Center, and editor in chief of Harvard Medical School’s Annual Report on Prostate Diseases. In many cases, Garnick pointed out, years will pass before any cancer cells that might be circulating in the body form tumors that can damage health.

But Garnick cautioned against a one-size-fits-all approach. Immediate hormone therapy is warranted if the relapse occurs soon after primary treatment, if the PSA level begins doubling quickly, or if the man had initially been treated for a high-grade, advanced prostate cancer and PSA either never became undetectable or started to rise a short time after surgery. “In these cases, I prefer to begin hormone treatment early on,” Garnick said.