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Time to testosterone recovery following cessation of long-course luteinizing hormone-releasing hormone (LHRH) agonists in prostate cancer (PCa) varies significantly between patients. Absent or delayed recovery may have a detrimental impact on physical and mental health. However, it has been suggested that it may be related to improved PCa outcomes, analogous to the duration of hormone therapy in breast cancer. Our aim was to examine time to testosterone recovery following long-course LHRH agonists and explore whether delayed or failure of testosterone recovery influences PCa outcomes.

Data from 473 patients in the Pelvic IMRT Clinical Trial in Prostate Cancer were analysed. All patients received radiotherapy and a planned 3 years of hormone therapy for high-risk PCa. Subsequent testosterone levels and PCa outcomes were recorded.

376 patients were included (reasons for exclusion: PCa progression or death during hormone therapy, patient received androgen receptor antagonists alone, no testosterone levels recorded). Median follow up was 9 years, 2 months. Median time to recovery of testosterone to 10nmol/L from cessation of LHRH agonists was 53 months, with 173 patients (46%) ultimately achieving this (median time to and percent achieving levels of 6nmol/L and 2nmol/L were 22 months and 67%, 14 months and 88% respectively). Patients over the age of 65 had a longer median time to recovery to 10nmol/L (30 months in under-65s vs 106 months in over-65s, p<0.001). Median time to PCa recurrence was 125 months; 167 patients (44%) had experienced a recurrence at the time of data collection. Patients who failed to recover testosterone to 10nmol/L had a nonsignificant trend towards a longer time to recurrence (p=0.074, median time not reached vs 113 months). Similar trends were observed for 2nmol/L and 6nmol/L. Of the 173 patients who recovered to 10nmol/L, those who took more than two years to recover had a longer time to recurrence than those who recovered within two years (median 166 months vs 100 months, p=0.008) and a longer recurrence-free survival (130 months vs 96 months, p=0.002). Time to second line therapy from cessation of LHRH agonists between the groups was analysed to see if the longer time to recurrence was associated with the development of castration resistance in the delayed group. There was no difference in time to second line therapy between groups (p=0.98).

Testosterone recovery following long-course LHRH agonists is often delayed or absent, particularly in older patients, and patients should be counselled appropriately. Patients with delayed or absent testosterone recovery appeared to have delayed PCa recurrence, but such recurrences were associated with castration resistance, supported by the observation that there was no difference in time to second line therapy between patients with or without delayed recovery. Testosterone supplementation may be considered for men with ongoing andropausal symptoms and delayed testosterone recovery.