Prostate cancer: Brachytherapy linked to long-term risk of secondary malignancies

When cancer patients are treated with radiation, it's possible that the therapy itself may cause new tumors to form in the body later. Radiation kills cancer cells by damaging their DNA, but if the treatments cause genetic damage to normal cells near the radiation target, there's a small risk that these secondary malignancies may arise over time.

Just over 10 years ago, Canadian researchers set out to assess the risk of secondary malignancy among men with prostate cancer who were treated with a type of radiation called brachytherapy. Unlike radiation delivered from sources outside the body, brachytherapy is accomplished by implanting dozens of radioactive pellets, or "seeds," directly into the tumor site. Those seeds, which are never removed, emit radiation at a dose that declines toward zero over the course of a year.

Brachytherapy has the advantage of convenience. Instead of traveling for repeat sessions of radiation, men need only one treatment, usually given in an outpatient setting. But brachytherapy is also falling out of favor, in part because newer types of external beam radiation deliver high-precision doses with fewer side effects.

Study methodology and results

The Canadian study compared rates of secondary malignancies in the pelvis among men treated either with brachytherapy or with surgery to remove the prostate. All the treatments took place in British Columbia between 1998 and 2000. The brachytherapy group included 2,418 men with an average age of 66, while the surgically-treated group contained 4,015 men whose average age was 62. Within that group, 2,643 men had been treated with surgery alone, and 1,372 men with surgery plus external beam radiation given later.

After median follow-ups of between 5.8 years (brachytherapy) and 6.4 years (surgery), the study team reported in 2014 that there was no difference in rates of secondary malignancies between the groups, or with cancer incidence in the general population.

But that's no longer the case: In April 2024, the researchers published updated findings. This time, rates of new cancers in the pelvis — including the bladder and rectum — were higher in the brachytherapy group. Specifically, 6.4% of brachytherapy-treated men had secondary malignancies at 15 years of follow-up, increasing to 9.8% after 20 years. By contrast, 3.2% and 4.2% of surgically-treated men developed secondary pelvic malignancies over the same durations. There was no difference in deaths from secondary malignancies between the groups.

The strength of the association with bladder cancer in particular is "similar to that seen with smoking," wrote the author of an accompanying editorial. Results from the study "should be considered when treating men with localized prostate cancer who have a long life expectancy," the authors concluded.

Commentary from experts

"I do believe that this study reveals a dark truth about radiation for prostate cancer that has been long suspected," says Dr. Anthony Zietman, a professor of radiation oncology at Harvard Medical School and Massachusetts General Hospital, and a member of the advisory and editorial board for the Harvard Medical School Guide to Prostate Diseases. "As the decades pass after radiation therapy of any kind — brachytherapy or external beam — the risk for radiation-induced malignancies rises.

"These malignancies are usually in adjacent organs like the bladder and rectum, or within the prostate itself. They may be very curable, and thus the survival rates are the same for radiation or surgically treated patients, but there is little doubt that, for these patients, they represent a 'sting in the tail' long after the radiation has been given and forgotten. This data certainly gives us pause when offering radiation to very young men with several decades of life expectancy ahead of them, and it also reminds us of the value of follow-up visits."

"The fact that second cancers arise in the area where radiation was given is not surprising, but the magnitude of the long-term increases is concerning," added Dr. Marc 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. "There are other common and troublesome urinary side effects of brachytherapy — independent of second cancers — that patients should fully consider before selecting it as a treatment option. This is especially true given the availability of other convenient and similarly effective prostate cancer therapies."