Testosterone Recovery Profiles After Cessation of Androgen Deprivation Therapy for Prostate Cancer

Abstract

Introduction Androgen deprivation therapy (ADT) is frequently used in the treatment of prostate cancer worldwide. Variable testosterone (T) recovery profiles after ADT cessation have been cited. Aim To evaluate T recovery after cessation of ADT. Methods We reviewed our institutional prospectively maintained database of patients with prostate cancer who received ADT. Serum early morning total T (TT) levels, collected at baseline and periodically after ADT cessation, were analyzed. Patient age, baseline T level, duration of ADT, and presence of diabetes and sleep apnea were selected as potential predictors of T recovery. 3 metrics of T recovery after 24 months of ADT cessation were analyzed: return to non-castrate level (TT > 50 ng/dL), return to normal (T > 300 ng/dL), and return back to baseline level (BTB). Multivariable time-to-event analysis (Cox proportional hazards), χ2 test, logistic regression model, and Kaplan-Meier curve were performed to define impact of the above predictors on time and chance of T recovery. Main Outcome Measures Time and chance of T recovery to non-castrate level (TT > 50 ng/dL), return to normal (T > 300 ng/dL), and return BTB. Results 307 men with a mean age of 65 ± 8 years were included. Mean duration of ADT was 17 ± 25 months, and median follow-up was 31 ± 35 months. Mean TT values were 379 ng/dL at baseline and 321 ng/dL at >24 months. At 24 months after cessation of ADT, 8% of men remained at castrate level, 76% returned to TT >300 ng/dL, and 51% had returned BTB. Lower baseline T levels (TT < 400 ng/dL) and ADT duration >6 months were associated with a lower likelihood of recovery to normal TT at 24 months. Age >65 years and receiving ADT for >6 months were significantly associated with a slower T recovery. Clinical Implications T recovery after ADT is not certain and may take longer than expected. Considering the range of side effects of low T, we believe that these findings must be discussed with patients before initiating such therapies. Strengths & Limitations Our strengths consisted of a relatively large database, long follow-up, and clinically meaningful endpoints. Limitations included the retrospective design of the study. Conclusion T recovery rates after ADT cessation vary according to patient age, ADT duration, and baseline T levels. Approximately one-quarter of patients failed to normalize their TT level, and one-tenth of men remained at castrate levels 24 months after ADT cessation.

Impact of Sequencing of Androgen Suppression and Radiation Therapy on Testosterone Recovery in Localized Prostate Cancer

“…In another single-institutional retrospective study by Nascimento et al, coexisting diabetes and older age were associated with delayed normalization of testosterone. 10 In contrast, Murthy et al found no correlation between age and time to testosterone recovery to >6 nmol/L. In this small study of 56 patients who were treated with neoadjuvant ADT followed by prostate radiation therapy (64-74 Gy), the majority had normalized testosterone by 1 year after the last ADT injection.…”

“…Time to full testosterone Some of the findings of our study, such as an association between increasing age, lower baseline testosterone level, or diabetes and longer testosterone recovery, concur with previous studies. 8,[10][11][12]26 Based on a multivariable Cox regression, Spiegel et al found a significant association between testosterone recovery and pretreatment testosterone level, ADT duration, and body mass index, respectively. 11 In this study, the 2-year cumulative incidence of testosterone recovery was 65.7% in patients treated with short-term ADT (median duration: 6 months; range, 3.0-18.4 months) and 53.1% in those treated with long-term ADT (median duration: 24.3 months; range, 3.0-41.9 months).…”

“…27 The testosterone recovery rate in this study was slightly faster compared with ours. However, there was notable heterogeneity among these studies with respect to use of radiation therapy as a primary versus adjuvant or salvage local therapy, 10,11 use of external beam radiation therapy or brachytherapy, 10,11 time-dose-fraction schedules, duration and timing of ADT with radiation therapy, [9][10][11]27 and definition of testosterone normalization, among others. Additionally, inconsistency in the formulation and number of cycles of luteinizing hormoneereleasing hormone agonists in these studies could have confounded the testosterone recovery kinetics.…”

“…The recovery depends on several factors, such as age, body mass index, and comorbidities such as diabetes mellitus, among others. [8][9][10][11][12] Furthermore, delivery of local radiation therapy has been found to result in a transient decline in serum testosterone level in men with LPCa. 13,14 However, it remains unknown whether the sequencing of ADT with local radiation therapy has any impact on kinetics of testosterone recovery after treatment completion.…”

Negative impact of neoadjuvant hormonal therapy on detecting biochemical recurrence after radical prostatectomy

“…For NHT, a luteinizing hormone releasing hormone (LHRH) agonist/antagonist and/or antiandrogen drug are usually selected. Several previous studies demonstrated that testosterone recovery to the normal level after hormonal therapy took several months [16][17][18][19][20][21][22][23]. On the other hand, the duration that NHT affects the pattern of BCR after RP has not been examined.…”