In Patients With Unfavorable Intermediate-Risk Prostate Cancer, Brachytherapy Improved Overall Survival Compared with External-Beam Radiotherapy

For men with unfavorable intermediate-risk (UIR) prostate cancer, National Comprehensive Cancer Network guidelines include 2 options for definitive radiotherapy. These options include external-beam radiotherapy (EBRT) with 4 to 6 months of androgen deprivation therapy (ADT) or EBRT plus a brachytherapy boost, with or without ADT. However, brachytherapy alone, with or without ADT, is not recommended for UIR prostate cancer. Nevertheless, brachytherapy enables considerably greater dose escalation than EBRT, but data on the use of definitive brachytherapy in UIR prostate cancer are limited.

To test the hypothesis that men treated with brachytherapy have rates of survival comparable with those of men treated with EBRT, researchers at 4 US cancer centers retrospectively reviewed the National Cancer Database records of nearly 32,000 men diagnosed with UIR prostate cancer between 2004 and 2015 (JNCCN. 2022;20(4):343-350). 

“Relative to favorable intermediate-risk (FIR) disease, men with UIR disease have higher rates of biochemical recurrence, metastatic recurrence, and death from prostate cancer,” wrote Neal Andruska, MD, PhD, Department of Radiation Oncology, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, and colleagues. “The addition of ADT to EBRT is associated with improved biochemical control and is considered standard of care, but the benefit of ADT in combination with BT [brachytherapy] is less well defined.”

The researchers stratified the participants into 4 groups: 1) nearly 13,000 who received EBRT; 2) nearly 13,000 who received EBRT plus ADT; 3) roughly 4500 who received brachytherapy; and 4) roughly 1300 who received brachytherapy and ADT.

The researchers used inverse probability of treatment weighting to adjust for covariable imbalances and weight-adjusted multivariable analysis with Cox regression modeling to compare overall survival (OS) hazard ratios (HRs).

As a result, the researchers found that, compared with EBRT alone, EBRT plus ADT, brachytherapy alone, and brachytherapy plus ADT were associated with improved OS. Relative to EBRT alone, the HR for EBRT plus ADT was 0.92 (95% confidence interval [CI], 0.87 to 0.97; P=.002), the HR for brachytherapy alone was 0.90 (95% CI, 0.83 to 0.98, P=.001), and the HR for brachytherapy plus ADT was 0.78 (95% CI, 0.69 to 0.88; P<.01).

Moreover, brachytherapy was associated with better OS than that for EBRT whether or not patients were treated with ADT. Relative to EBRT alone, the HR for those treated with brachytherapy but not ADT was 0.92 (95% CI, 0.84 to 0.99; P=.03), and the HR for those treated with brachytherapy plus ADT was 0.84 (95% CI, 0.75 to 0.95; P=.004).

In addition, after 10 years of follow-up, 56% of those who received EBRT and 63% of those who received brachytherapy were still alive (P<.001). 

“Definitive brachytherapy was associated with improved OS compared with EBRT. The addition of ADT to both EBRT and definitive brachytherapy was associated with improved OS. These results suggest that definitive brachytherapy should be considered as an option for men with UIR prostate cancer,” Dr Andruska and team concluded.