The standard of care for metastatic castration-sensitive prostate cancer has evolved. ADT plus an ARPI is now the baseline treatment for nearly every patient. Referring to it as 'intensification' is outdated and misrepresents its role as the new standard.
Registrational clinical trials for prostate cancer drugs enroll patients who are substantially younger (median age 67-69) and healthier than the typical real-world patient (median age 73-74). This gap means trial data on efficacy and safety doesn't perfectly apply to the majority of patients seen in clinic.
The Department of Veterans Affairs (VA) is a premier source for real-world data because it uniquely combines clinical information from electronic medical records with its own insurance claims data. This integration of 'both sides of the data house' provides a complete patient picture that is difficult to replicate elsewhere.
To generate reliable findings from real-world data, researchers must avoid data dredging. The best practice is to simulate a 'target trial' by creating a formal protocol with pre-defined inclusion criteria and a statistical plan, mirroring the rigor of a prospective clinical trial. This approach is even guided by the FDA.
A VA study using real-world data confirms that androgen receptor pathway inhibitors (ARPIs) combined with ADT significantly improve survival in elderly (>75), frail, and high-comorbidity prostate cancer patients. This evidence directly addresses clinician hesitancy to treat these vulnerable populations with standard-of-care combination therapy.
An effective, informal frailty assessment can be done by observing a patient's movement. The time it takes for them to stand up from a chair in the waiting room and their walking speed into the clinic functions as a 'time to get up and go' test, providing critical data on their functional status.
ADT monotherapy is an obsolete strategy for metastatic prostate cancer. For patients too frail for standard ADT+ARPI combination therapy, enzalutamide monotherapy is a superior alternative. It offers effective treatment that can be quickly stopped to reverse side effects if tolerance issues arise, unlike injectable ADT.
Real-world data from the VA suggests abiraterone is associated with increased hospitalizations for cardiovascular events, infections, and acute kidney injury compared to other ARPIs. This finding prompts clinicians to favor AR antagonists like enzalutamide in older, comorbid patients at higher risk for these complications.
A quarter of patients with metastatic prostate cancer die from cardiovascular disease, not their cancer. This statistic mandates that oncologists actively manage patient comorbidities by assembling a specialist team, engaging primary care, and emphasizing lifestyle interventions alongside cancer treatment to improve overall survival.
While clinical trials raised concerns about falls with enzalutamide, real-world data from the VA’s frail, comorbid population did not show this signal. A possible explanation is that the baseline rate of falls in this vulnerable population is already so high that it masks any drug-specific effect, a key insight for risk assessment.