Risk of Death Before and After Metastasis in High-Risk Localized and Locally Advanced Prostate Cancer Patients Undergoing Radical Prostatectomy or Radiotherapy as Primary Treatment in the United States: A Retrospective Study

It is well-known that prostate cancer (PC) death rates increase after metastasis, but the magnitude of the change is unclear, especially with recent novel therapies in metastatic PC. We examined changes in mortality after metastasis in high-risk localised and locally advanced PC (HR-LPC/LAPC) undergoing primary treatment with radical prostatectomy (RP) or radiotherapy with/without androgen deprivation therapy (RT±ADT).

ConcertAI Patient360TM, which provides data from predominantly medical oncologists, was queried from January 2000 – October 2022 for men with HR-LPC/LAPC who underwent primary treatment with either RP or RT±ADT. Pre-/post-metastasis survival was analysed using Kaplan-Meier estimation to generate pre-/post-metastasis 5-year mortality rates. 5-year Standardised Mortality Ratios (SMR) were computed as the ratio of observed 5-year mortality rate in HR-LPC/LAPC patients receiving RP or RT±ADT to the age-adjusted mortality rate for the general male population in the United States.

Among 5,008 patients identified as HR-LPC/LAPC patients, 1,696 underwent RP and 686 RT±ADT. Patients undergoing RP were younger (median age at RP=63 vs RT±ADT=69). During follow-up (median=7.5 years), around half of the patients developed metastases in both groups. In RP patients, the relative risk of death increased after metastasis by 8-fold [95% Confidence Interval (CI) 6.16,9.93] (5-year pre-metastasis SMR: 0.50 [95% CI 0.39,0.62]; and 5-year post-metastasis SMR: 3.86 [95% CI 3.62,4.11]). In the RT±ADT group, the increase was 5-fold [95% CI 3.97,6.84] (5-year pre-metastasis SMR: 0.72 [95% CI 0.55,0.91]; and 5-year post-metastasis SMR: 3.71 [95% CI 3.32,4.07]).

This retrospective study of patients seen predominantly by medical oncologists demonstrated that mortality risk in HR-LPC/LAPC patients significantly increased after metastasis, suggesting therapies delaying disease progression in this setting may improve overall survival. Since study data comes predominantly from oncology practices likely explaining the bias of very high metastases rates, future research can consider alternative data sources (i.e., data from urology practices) to further investigate this topic.