More Aggressive Combination Therapy Offers Survival Advantage for High-Risk Prostate Cancer Patients

By Thomas Crocker
Friday, January 18, 2019

Men with locally or regionally advanced prostate cancer who receive radical prostatectomy followed by radiation therapy live longer than those who receive radiation therapy plus androgen deprivation therapy (ADT), according to a recent study.

Clinical guidelines in the U.S. and Europe call for the use of combination therapy for men with high-risk prostate cancer, but there has been a dearth of evidence as to which of two commonly used multimodal therapies — radical prostatectomy plus radiation therapy and radiation therapy plus ADT — is more effective, according to Thomas Jang, MD, MPH, FACS, urologic oncologist at Rutgers Cancer Institute of New Jersey. Dr. Jang, Grace Lu-Yao, PhD, MPH, Associate Director of Population Science at the Sidney Kimmel Cancer Center at Thomas Jefferson University in Philadelphia, and a group of researchers set out to change that.

Procedural Renaissance?

Using patient information from the SEER–Medicare database, researchers identified 13,856 men with locally or regionally advanced prostate cancer and compared the outcomes of those who received surgery plus radiation with those whose treatment was radiation plus ADT.

After 10 years, men who received surgery plus radiation — the more aggressive treatment — enjoyed a 15-point survival advantage, 89 percent to 74 percent, compared with men who received radiation and ADT.

The results, published in the journal Cancer, are consistent with other studies that indicate aggressive treatments, including radical prostatectomy, are increasingly common for high-risk patients.

“Surgery in this group of men has not been popular historically ... because surgery in this setting can be very technically challenging and is associated with an increased risk of positive margins, so radiation up front with ADT has traditionally been offered to these patients,” Dr. Jang says. “There’s some emerging, preliminary data that a select group of men with advanced prostate cancer can benefit from more aggressive local therapies, whereas previously these men were offered less aggressive approaches. ... [T]he treatment paradigm may be changing.”

Two 2017 studies underscore Dr. Jang’s point. One, published in Prostate Cancer and Prostatic Diseases, found that use of radical prostatectomy to treat high-risk prostate cancer increased from 26 percent in 2004 to 42 percent in 2013. A second study, in The Journal of Urology, found that men with locally advanced prostate cancer who underwent radical prostatectomy experienced less overall and prostate-specific mortality than those who received radiation.

The Importance of Informed decision-Making

As with any observational study, Dr. Jang and Lu-Yao encountered limitations in adjusting for confounding factors, such as age, that may have influenced patient outcomes. Had they been able to achieve perfect adjustment, they agree that the survival disparity might have been smaller than 15 percent. However, the greater efficacy of the more aggressive combination therapy did not surprise the researchers.

“Both radical prostatectomy and radiation therapy [alone] have been used for curative intent, and both are pretty strong in control of disease,” Lu-Yao says. “ADT has been used ... usually for more palliative intent. ... If you think of radical prostatectomy and radiation therapy, it’s two curative-intent approaches together. Kind of theoretically, I would expect radical prostatectomy and radiation therapy to be more effective in controlling disease.”

The more aggressive therapy, however, is not without risk: In the study, men who underwent surgery and radiation were more likely to experience urinary incontinence and erectile dysfunction. That, Lu-Yao says, “speaks to the importance of shared decision-making with patients, which is why it’s important to support research to generate data for patients and doctors to make better decisions.”

Adam Dicker, MD, PhD, FASTRO, Senior Vice President and Professor and Chair of Enterprise Radiation Oncology at Jefferson Health in Philadelphia, says the study is valuable because it confirms what many prostate cancer specialists have long suspected about the efficacy of aggressive combination therapy for high-risk patients.

“Some people will view this as confirmatory to the way they practice, and for others, this may shift their thinking,” says Dr. Dicker, who was not involved with the study. “For ... those of us who are 100 percent focused on prostate cancer and have been doing leading-edge research, it confirms what we knew already, although it’s one thing to suspect something and another to have some data.”

Dr. Jang, Lu-Yao and other prostate cancer researchers eagerly await the results of an ongoing randomized trial by the Scandinavian Prostate Cancer Group comparing surgery plus radiation and radiation plus ADT. In the meantime, Dr. Jang says, either approach can yield long-term survival. Every patient, in collaboration with his physician, must weigh the risks and benefits of each.