Comparison of Multimodal Therapies Identifies Equivalent Mortality Outcomes, Improved Distant Metastases in High-Risk Prostate Cancer

Patients with high-risk prostate cancer with unfavorable clinicopathologic features who were treated with radical prostatectomy, external beam radiotherapy (EBRT), androgen deprivation therapy (ADT), and EBRT plus brachytherapy had equivalent prostate-specific mortality, while EBRT plus or minus brachytherapy yielded more favorable outcomes, according to a study comparing the outcomes garnered from guideline-concordant multimodal therapies in JAMA Network Open.

Investigators identified an association between significantly improved prostate-specific cancer mortality and treatment with EBRT plus brachytherapy (subdistribution HR [sHR], 0.78; 95% CI, 0.63-0.97; P = .03) and EBRT alone (sHR, 0.70; 95% CI, 0.53-0.92; P = .01) compared with radical prostatectomy. Notably, there was no difference in prostate cancer-specific mortality with EBRT plus brachytherapy vs EBRT alone (sHR, 0.89; 95% CI, 0.67-1.18; P = .43).

A total of 6004 patients were enrolled with a median age of 66.4 years. Overall, 52.9% of patients underwent a radical prostatectomy, 30.5% underwent EBRT, and 16.6% underwent EBRT plus brachytherapy. In the overall population, 50.4% of patients received optimal radical prostatectomy, 48.0% had optimal EBRT, and 46.1% had optimal EBRT plus brachytherapy.

A total of 76.2% of patients received EBRT alone and 89.7% received EBRT plus brachytherapy and ADT. The median duration of ADT in all patients was 22 months for those receiving EBRT alone vs 12 months for those receiving EBRT plus brachytherapy (P <.001); for optimal treatment the median duration of ADT was 28 months vs 24 months in each respective group (P <.001).

Among patients who received radical prostatectomy, 10.9% underwent adjuvant radiotherapy, and 26.7% underwent salvage radiotherapy. Among those receiving optimal treatments 12.4% and 31.9%, respectively.

The adjusted 5-year prostate-specific cancer mortality rates were 5.3% (95% CI, 3.9%-7.2%) for those who received radical proctectomy, 4.6% (95% CI, 3.7%-5.8%) for EBRT, and 4.0% (95% CI, 3.0%-5.4%) for EBRT plus brachytherapy. For those with distant metastases, the adjusted 5-year rates were 18.4% (95% CI, 16.7%-20.2%) for radical proctectomy, 11.7% (95% CI, 10.1%-13.5%) for EBRT, and 6.8% (95% CI, 5.4%-8.4%). For those who received EBRT alone (sHR, 0.50; 95% CI, 0.44-0.58; P <.001) and EBRT plus brachytherapy (sHR, 0.25; 95% CI, 0.16-0.37; P <.001), the risk of distant metastases was reduced compared with those receiving radical. Additionally, the risk of distant metastases was reduced for those who received EBRT plus brachytherapy, similar to EBRT alone (sHR, 0.52; 95% CI, 0.33-0.80; P = .003).

In a subcohort analysis, investigators reported that 5-year prostate cancer-specific mortality for those receiving optimal radical prostatectomy was 3.4% (95% CI, 2.4%-4.8%), 3.3% (95% CI, 2.3%-4.8%) for optimal EBRT, and 3.4% (95% CI, 2.3%-4.8%) for optimal EBRT plus brachytherapy. There were no differences in prostate cancer-specific mortality in any of the subcohorts, including optimal EBRT vs optimal radical prostatectomy (sHR, 0.76; 95% CI, 0.52-1.09; P = .14).

The adjusted 5-year incidence rate for distant metastasis among those receiving optimal radical prostatectomy was 13.4% (95% CI, 11.7%-15.4%), 8.7% (95% CI, 7.1%-10.6%) for optimal EBRT, and 4.2% (95% CI, 2.8%-6.2%) for optimal EBRT plus brachytherapy. For patients receiving optimal radical proctectomy, there was a reduction in time to distant metastases for those receiving optimal EBRT (sHR, 0.48; 95% CI, 0.38-0.61; P <.001) or optimal EBRT plus brachytherapy (sHR, 0.25; 95% CI, 0.16-0.37; P <.001). A reduction in the risk of distant metastases was observed in those who received EBRT plus brachytherapy vs EBRT alone (sHR, 0.52; 95% CI, 0.33-0.80; P = .003).

Reference

Kishan AU, Karnes RJ, Romero T, et al. Comparison of multimodal therapies and outcomes among patients with high-risk prostate cancer with adverse clinicopathologic features. JAMA Netw Open. 2021;4(7):e2115312. doi:10.1001/jamanetworkopen.2021.15312