Promising therapy if PSA rises after prostate cancer surgery

Many men who undergo surgical treatment for prostate cancer (a radical prostatectomy) live out their lives without a recurrence of their disease. But 20% to 40% of them will experience a rise in prostate-specific antigen (PSA) levels within 10 years of the operation. PSA should be undetectable in blood if the prostate has been removed, so elevated levels signify that the cancer may have returned. Doctors call this a biochemical relapse, and ordinarily they treat it by giving radiation to the prostate bed, which is where the prostate resided before it was taken out. Referred to as pelvic bed radiation therapy, or PBRT, this sort of treatment often succeeds in bringing PSA back down to zero for years.

Now, a large study shows that PBRT is even more effective when combined with other treatments. The findings are a potential game-changer for men experiencing a biochemical relapse after radical prostatectomy.

Funded by the National Cancer Institute, the SPPORT phase 3 clinical trial was conducted at nearly 300 medical centers across the United States, Canada, and Israel. A total of 1,797 men were enrolled between 2008 and 2015, all with post-surgical PSA levels ranging between 1 and 2 nanograms per milliliter (ng/mL).

The subjects were randomly assigned in roughly equal numbers to one of three groups. The men in group 1 got PBRT by itself, while men in group 2 got PBRT combined with four to six months of androgen deprivation therapy, or ADT. (Also known as hormonal therapy, ADT blocks testosterone, a hormone, or androgen, that fuels growing prostate tumors.) The men in group 3 got PBRT, ADT, and also radiation to the pelvic lymph nodes, where prostate cancer typically goes first if it begins to spread. The investigators wanted to know which of these three strategies is most effective at keeping disease progression at bay.

Results, side effects, and what's next

According to their results, the more intensive treatments led to better outcomes. Just over 70% of men in group 1 were still avoiding disease progression after five years, compared with 80.3% of men in group 2 and 87.4% of men in group 3. More specifically, 145 of the men in group 1 developed further PSA elevations during the follow-up period, compared with 104 men in group 2 and 83 men in group 3. Similar trends were observed with respect to how many men developed metastases, or cancer that becomes resistant to hormonal therapy after it begins to spread.

The more intensive treatments also had more short-term side effects, especially diarrhea. But differences in side effects between the three groups disappeared after three months.

The authors emphasized that longer follow-up is still needed to confirm whether adding ADT and pelvic node radiation to PBRT actually lengthens survival. Moreover, the study did not evaluate a newer therapeutic strategy for biochemical relapse, where doctors use novel imaging methods to find exceedingly small metastases throughout the body that they treat directly with radiation.

Dr. Marc Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and editor of the Harvard Health Publishing Annual Report on Prostate Diseases, says it's important for men to understand that any measurable amount of PSA after a radical prostatectomy is abnormal and requires further evaluation. "The time-honored normal PSA range of 0 to 4 ng/mL no longer applies when men have had their prostates surgically removed," he says. "Evidence of further benefits from adding ADT and pelvic radiation during this study is significant. Whether this represents a new standard of care in biochemical relapse requires additional follow-up."