Risk of recurrence.
Even though biochemical recurrence is the primary endpoint of countless trials, it’s not borne out as a reliable surrogate for prostate cancer death. That's probably because recurrence/persistence of low-risk disease is still low risk. Here is a pooled analysis of two phase 3 trials assessing duration of ADT in addition to radiation for early-stage (trial 1 = cT1-2N0) or locally-advanced (trial 2 = pN1-2 or cT2c-4N0-2) prostate cancer. Compared with early-stage disease, biochemical recurrence of locally advanced prostate cancer was associated with a starkly higher risk of all-cause mortality (HR 3.98). The authors thus argue for ADT intensification (e.g., adding abiraterone or enzalutamide) at the time of biochemical recurrence after treatment for locally-advanced, but not early-stage, disease. | King, JAMA Netw Open 2021