Age and Treatment Intensification in Metastatic Hormone-Sensitive Prostate Cancer

Area of Science:

• Oncology
• Geriatric Medicine
• Clinical Trials

Background:

• Older men with metastatic hormone-sensitive prostate cancer (mHSPC) often have comorbidities and higher non-cancer mortality.
• The impact of age on the survival benefits of systemic treatment intensification (TI) in mHSPC is not fully understood.

Purpose of the Study:

• To investigate if age influences the overall survival (OS) benefit of treatment intensification (TI) using androgen receptor pathway inhibitors (ARPIs) and/or chemotherapy in mHSPC.
• To analyze the differential effects of TI on OS in younger versus older men with mHSPC.

Main Methods:

• Systematic literature search of phase 3 randomized trials in mHSPC (2010-2024).
• Meta-analysis and meta-regression of aggregate data, with age dichotomized at 70 or 75 years.
• Validation using individual patient data (IPD) from three key trials (TITAN, ARASENS, LATITUDE).

Main Results:

• Eleven trials (13,648 patients) showed TI improved OS (HR 0.73).
• Significant interaction between age and TI on OS (P<0.001); younger men had greater benefit (HR 0.63) than older men (HR 0.82).
• In older men, TI showed no OS benefit with triplet therapy (HR 0.94) and limited benefit in low-volume disease (IPD HR 0.89).

Conclusions:

• Age significantly interacts with the OS benefit of TI in mHSPC.
• Treatment strategies for older men (≥70 years) with mHSPC, particularly those with low-volume synchronous disease, require careful consideration, potentially favoring radiotherapy.