Excitement for Brachytherapy in Prostate Cancer

Adding supplemental external beam radiotherapy (EBRT) did not improve outcomes in higher-risk cancer patients who had brachytherapy, according to the long-term results of two trials.

Specifically, adding EBRT did not improve biochemical failure (BF) rate or prostate cancer specific mortality (PCSM) in patients who were implanted with brachytherapy palladium 103. The size of the EBRT dose also did not appear to have an effect on BF or PCSM. BF was defined as a prostate-specific antigen of greater than 0.4 ng/mL after nadir.

Long-Term Results of Two Trials Combined

Martin T. King, MD, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts, presented the findings of the two “44/20/0” trials at the American Society for Radiation Oncology (ASTRO) 2024 Annual Meeting, on Monday. A total of 630 patients were included in the two trials.

The first compared 44 Gy of EBRT with 90 Gy of brachytherapy against 20 Gy of EBRT with 115 Gy of brachytherapy. The second compared 20 Gy of EBRT with 115 Gy of brachytherapy against 125 Gy of brachytherapy alone.

“There was actually no difference in treatment arms for either trial,” King said in an interview. 

He pointed out that of the patients who had brachytherapy alone, about 50% had unfavorable intermediate-risk disease. Still, even with these higher-risk patients (those with unfavorable intermediate risk), “their risk of biochemical failure was only about 5%” when evaluated at the 13-year mark.

Among all of the patients who received 20 Gy EBRT, their risk of BF at 13 years was 4.9%. For those who received 44 Gy EBRT, that risk was 9.2% 13 years out.

Low-dose rate brachytherapy is a curative treatment option for prostate cancer, and excellent long-term oncologic outcomes have been achieved in both the monotherapy and boost settings, King said. “However, the selection of monotherapy or boost regimens remains controversial particularly for intermediate-risk disease.”

He stopped short of calling these results practice-changing, but said, “patients with favorable intermediate-risk disease or unfavorable intermediate-risk disease with a single risk factor likely could be candidates for brachytherapy alone.”

“This work shows us that when you do implant aggressively and provide good quality implants, you can get very good results without doing external beam, without doing hormonal therapy,” he noted. 

“I think a lot of patients are looking for treatments like this” and can avoid multiple weeks of EBRT, King added.

Greater Toxicity with Combined Treatment 

The combination regimen takes longer to give and has also been associated with greater toxicity than just giving the brachytherapy alone. 

“More effort to try to better direct the brachytherapy toward the tumor can lead to better outcomes,” King said. “It increases the excitement for brachytherapy, and it’s a great way for radiation oncologists and urologists to collaborate.” 

“These are important data as the long-term results — a median follow-up of 11.8 years — provide reassuringly low rates of biochemical failure overall, in both trials,” Amar Kishan, MD, Professor and Executive Vice Chair of Radiation Oncology at University of California Los Angeles, said in an interview. 

“In the 44/20 trial, nearly 60% of patients had unfavorable intermediate risk disease (20% had high risk disease) and in the 20/0 trial, nearly 50% had unfavorable intermediate risk disease (greater than 5% had high risk disease).” 

Results Should not Be Generalized to High-Risk 

Kishan, who was not part of the research, said these data demonstrate that brachytherapy alone is sufficient for treating unfavorable intermediate risk prostate cancer, but not enough is known about its use for high-risk disease. 

“Patients with high-risk prostate cancer were not well represented, particularly in the 20/0 trial, so this conclusion should not be extrapolated to that group,” he said.

An important caveat is that hormonal therapy, “known to improve outcomes,” was not widely used with participants in the trial, Kishan said.

“Whether adding hormonal therapy to both arms would have altered the results is not clear, though the provided analysis does not suggest that it would,” he said.

King receives grants/research funding from Bayer Health care and Palette Life Sciences and salary support from Palette Life Sciences. Two other coauthors reported disclosures. 

Kishan receives personal fees from Boston Scientific, Novartis, Varian Medical Systems, Lantheus, and Janssen Pharmaceuticals.

Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News, Northwestern magazine, and Nurse.com and was an editor at the Chicago Sun-Times, The Cincinnati Enquirer, and St. Cloud Times. Follow her on X: @MLfrellick.