br Despite the overwhelming data
Despite the overwhelming data supporting the use of LHRH agonists and the broad implementation of both STADT and LTADT with RT in clinical practice, the time course and extent of BMS 986120 recovery after discontin-uation of ADT is not well understood. Although time to testosterone recovery has been studied previously, the available data7-18 suggest a wide range of time for testos-terone recovery (TR) with both STADT and LTADT, and limited cohorts of patients were examined in these studies. Given the impact of ADT on quality of life, we sought to identify factors affecting testosterone recovery after com-bined ADT and RT and aimed to create a nomogram to predict TR in a clinical setting.
Methods and Materials
We identified consecutive localized prostate cancer patients treated with concurrent curative-intent RT and ADT at 2 academic medical centers from January 2011 through October 2016. ADT duration was at the discretion of the treating physician. Typically, intermediate-risk patients received STADT and high-risk patients received LTADT. All patients were required to have a documented baseline testosterone level before ADT initiation. Serum
testosterone levels were measured during ADT treatment and after ADT cessation. The testosterone assay used within the training cohort was the ADVIA Centaur Testosterone II assay, which is a competitive immunoassay using direct chemiluminescent technology. Testosterone in the sample competes with acridinium ester-labeled hapten in the Lite Reagent for binding with antitestosterone sheep monoclonal antibody. The assay used within the validation cohort was an access testosterone competitive binding assay with validated analytical measurement range. Patients were followed with an initial 3-month visit after treatment completion and then with follow-up visits every 6 to 12 months depending on the clinical scenario and individ-ual provider preference. Follow-up visits included updated history, physical examination, and prostate-specific antigen and testosterone laboratory tests. International Index of Erectile Function (IIEF-5) questionnaires19 were prospec-tively collected by both clinics as part of routine care. For this study, patient and treatment characteristics and quality-of-life data were retrospectively collected from electronic medical records.
Patients were stratified according to ADT plan (ST vs LT). ST was defined at 6 months of therapy and LTADT was defined as >6 months of therapy. The primary endpoint of the study was TR, defined as time from the date of the last ADT injection to the date of testosterone normalization. Testosterone normalization was defined according to measured testosterone levels with a lower laboratory limit of normal of 240 ng/dL for the training cohort and 175 ng/ dL for the validation cohort. Secondary endpoints were duration of castrate testosterone (<20 ng/dL) from the date of last ADT injection, biochemical progression-free sur-vival (BPFS, defined as nadir þ 2), and descriptive patient-reported quality-of-life data.
The cumulative incidence rates of TR were estimated from the cumulative incidence function. Gray’s test was used to test for differences in cumulative incidence rates between the 2 groups. The Kaplan-Meier method was used to estimate time to TR and BPFS. IIEF-5 data were analyzed at baseline and at the time of testosterone recovery.
Univariate and multivariate Cox regression analyses were then performed with patient data from site 1, which was the training cohort, and included variables selected
based on clinical hypothesis or results from prior studies.17,20 Variables that were found to be significant