Researchers identify optimal treatment for aggressive prostate cancer

External beam radiotherapy plus brachytherapy boost and androgen deprivation therapy significantly lowered cancer-specific mortality and lengthened the time to distant metastasis in men with Gleason score 9 to 10 prostate cancer, according to findings published in JAMA.

Because the optimal treatment of Gleason score 9 to 10 prostate cancer is unknown, researchers sought to compare clinical outcomes of patients after definitive treatment.

“Patients with Gleason score 9 to 10 prostate cancer have particularly aggressive disease,” Amar U. Kishan, MD, assistant professor in the department of radiation oncology at UCLA, and colleagues wrote. “Because of this aggressive nature, a comparative outcomes analysis of external beam radiation therapy, external beam radiation therapy plus brachytherapy boost and radical prostatectomy could examine clinical outcomes of patients treated in a contemporary period while maintaining the statistical power to detect differences between modalities.”

The researchers performed a retrospective cohort study of 1,809 men with Gleason score 9 to 10 prostate cancer who were treated at 12 tertiary cancer centers (11 in the United States, one in Norway).

Prostate cancer-specific mortality served as the main outcome. Secondary outcomes included distant metastasis-free survival and OS.

Most men received external beam radiotherapy (n = 734; median age, 67.7 years), followed by radical prostatectomy (n = 639; median age, 61 years) and external beam radiotherapy with brachytherapy boost (n = 436; median age, 67.5 years).

Median follow-up was 7.2 years among men who underwent radical prostatectomy, 5.1 years among those who received external beam radiotherapy and 6.3 years among those who received radiotherapy plus brachytherapy.

The vast majority of men who received external beam radiotherapy alone (89.5%) or plus brachytherapy (92.4%) also received ADT.

The adjusted 5-year prostate cancer-specific mortality rate was 13% (95% CI, 8-19) among men who received external beam radiotherapy alone, 12% (95% CI, 8-17) for radical prostatectomy and 3% (95% CI, 1-5) for external beam radiotherapy plus brachytherapy.

Treatment with external beam radiotherapy plus brachytherapy appeared linked with lower prostate cancer-specific mortality than radical prostatectomy (HR = 0.38; 95% CI, 0.21-0.68) and external beam radiotherapy alone (HR = 0.41; 95% CI, 0.24-0.71)

Five-year incidence of distant metastasis was 24% for patients who underwent radical prostatectomy (95% CI, 19-30), as well as for those who received external beam radiotherapy alone (95% CI, 20-28). However, those who received external beam radiotherapy plus brachytherapy had a 5-year distant metastasis incidence rate of 8% (95% CI, 5-11).

Further, external beam radiotherapy plus brachytherapy appeared associated with a lower risk for distant metastasis than radical prostatectomy (HR = 0.27; 95% CI, 0.17-0.43) and external beam radiotherapy (HR = 0.3; 95% CI, 0.19-0.47).

The adjusted 7.5-year all-cause mortality rate was 17% (95% CI, 11-23) for patients who underwent radical prostatectomy compared with 18% (95% CI, 14-24) for external beam radiotherapy and 10% (95% CI, 7-13) for external beam radiotherapy plus brachytherapy.

External beam radiotherapy plus brachytherapy significantly reduced risk for all-cause mortality in the first 7.5 years of follow-up (vs. prostatectomy, HR = 0.66; 95% CI, 0.46-0.96; vs. external beam radiotherapy alone, HR = 0.61; 95% CI, 0.45-0.84).

However, after the first 7.5 years, the HRs were 1.16 (95% CI, 0.7-1.92) for radical prostatectomy and 0.87 (95% CI, 0.57-1.32) for external beam radiotherapy.

Researchers observed no significant differences between treatment with external beam radiotherapy alone or radical prostatectomy for prostate cancer-specific mortality, all-cause mortality or distant metastasis.

“Overall, these data suggest that treatment with external beam radiotherapy plus brachytherapy is significantly associated with better outcomes in this high-risk group of patients,” Kishan and colleagues wrote. – by Andy Polhamus

Disclosures: Kishan reports no relevant financial disclosures. Please see the full study for all other authors’ relevant financial disclosures.