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231 Background: Early biochemical detection and subsequent slow progression of recurrent prostate cancer after primary radiotherapy permit the delivery of potentially curative local salvage therapy (LST). Several LST options are available, including cryotherapy, brachytherapy (BT), and radical prostatectomy (RP). We studied the rates at which patients are offered, and receive LST after failure of primary radiotherapy. Methods: Patients with localized prostate cancer who received primary radiotherapy with curative intent between 1999-2000 were identified in the British Columbia radiotherapy database. Data on clinicopathologic features, primary therapy, PSA kinetics, and salvage therapy were collected retrospectively. We excluded patients with T4 tumors, PSA >40, or age >72 years at time of primary therapy. Biochemical recurrence (BCR) was defined by the Phoenix criteria. Patients were also deemed radiation failures if salvage therapy was started without meeting criteria for BCR. Results: Out of 1785 patients treated with radiation, 1067 met the inclusion criteria. Of these, 257 experienced BCR. Five patients received LST (3 RP, 2 BT). LST was considered in 11 other patients, but 2 were not referred for urologic opinion, and 9 declined intervention. 60 patients were considered ineligible for LST: 43 due to suspected metastasis and 17 due to other comorbidities. LST was unlikely to be offered to 80 patients due to age >75 at time of BCR. 59 additional patients appeared to be eligible for LST but there was no evidence that it was considered in the medical record. ADT was started within 12 months of BCR in 118 patients, and after at least one year of observation in another 66. Conclusions: Few patients were considered for LST in the study period, and only 5 received it. This review of practice patterns reveals a lack of uniform monitoring and treatment strategies in this challenging patient population, and indicates a need for more collaboration between all treating physicians, as well as with tertiary care centers.

Introduction Anti-factor VIII antibodies are a serious complication of factor replacement therapy in hemophilia A patients. Neutralizing antibodies could previously only be detected via the functional and gold-standard Bethesda assay with or without the Nijmegen modification. The introduction of an enzyme-linked immunosorbent assay (ELISA) screening test provides a less laborious alternative to the Bethesda assay and also has a high sensitivity. Unlike the Bethesda assay, the ELISA can potentially detect non-neutralizing antibodies, which raise the possibility of false positive screens. As it is important that both clinicians and the coagulation laboratory understand the clinical performance of ELISA screening, this study evaluated the sensitivity and specificity of ELISA and Bethesda assays used in both a laboratory validation study and in subsequent clinical experience. Methods Results from all active adult and pediatric congenital hemophilia A patients who underwent both Bethesda assay and ELISA in British Columbia, Canada as of July 2013 were included in this study. The sensitivity and specificity were compared to the provincial coagulation laboratory validation study of the GTI Factor 8 Antibody ELISA kit against the classical Bethesda assay conducted in both hemophilia A and normal controls in 2010. Optical density (OD) readings were retrieved for eligible samples and from the laboratory validation study. Results 35 samples from 26 different patients were used in the validation study performed in 2010. Of 147 adult and 86 pediatric hemophilia A clinic patients active during the study period, 56 samples from 16 adults and 17 children underwent concurrent Bethesda assay and ELISA screen between November 2010 and June 2013. Since ELISA implementation, 389 ELISA screens and 187 Bethesda assays were performed. ELISA screens resulted in the avoidance of Bethesda assays in 85% (330/389) of samples submitted during that period. Specificities and positive predictive values were lower in the clinical sample due to a larger number of false positives (n=18; 32%) relative to the validation study (n=3; 9%), while sensitivity and negative predictive values remained at 100% (Table 1). Interestingly, 67% (2/3) of false positive ELISA screens in the laboratory setting had Bethesda positive histories; however, in the clinical sample, only 6% (1/18) had a distant history of inhibitors. ODs were available for all validation study samples and for 54 clinical samples. Redefinition of our OD cutoff to improve specificity was prevented by false positive patients with strongly positive ODs. Conclusions The ELISA screen used in this setting is highly sensitive for anti-factor VIII antibody detection in congenital hemophilia A. However, compared to pre-clinical data, our 2.5 years of clinical experience reveals a high incidence of false positives resulting in a significantly lower specificity. Our approximate cost savings in British Columbia as a result of avoided Bethesda assays due to ELISA screens (n=330) is $90 per test, and may exceed $200 per test in the United States. Additional testing and follow-up on positive ELISA results can be an inconvenience in both time and blood sampling, especially in the pediatric population where inhibitor status is more closely monitored. The cost ramifications of this follow up testing could not be quantified in this study. The potential implications for the detection of non-neutralizing anti-FVIII antibodies in hemophilia A need to be further explored and long-term study and monitoring of these discrepant patients is warranted. Disclosures: No relevant conflicts of interest to declare.

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