Patrick Cotogno

Exceptional Duration of Radium-223 in Prostate Cancer With a BRCA2 Mutation

Clinical Practice PointsIt is now recognized that patients with prostate cancer have a higher rate of DNA repair gene mutations than previously appreciated.The prevalence of germline alterations in DNA repair genes may be as high as 11.8% in patients with metastatic prostate cancer.Several targeted agents for DNA repair defects (poly ADP ribose polymerase inhibitors and platinums) have shown increased sensitivity in the setting of biallelic breast cancer susceptibility gene 2 (BRCA2) loss.The mechanism of action of Radium‐223, a bone‐targeted radiopharmaceutical, raises the possibility of clinical exploitation among patients with a BRCA2 mutation.We hypothesize that the extraordinary duration of disease control with Radium‐223 described herein is owing to the presence of a unique sensitivity in patients with a BRCA2 mutation.

Characterizations of Clinical and Therapeutic Histories for Men With Prostate Cancer-Specific Mortality

BACKGROUND Careful descriptions of men with prostate cancer (PCa)-specific mortality are scant in nontrial settings. The present retrospective review describes the clinical characteristics, timelines, and treatment histories from initial presentation to death in a cohort of men with metastatic, castrate-resistant PCa (mCRPC). Unique to the present study is the unequivocal attribution of PCa death by a single experienced clinician. PATIENTS AND METHODS A total of 119 patients who had been treated at Tulane Cancer Center and had died of mCRPC from 2008 to 2015 were studied through a retrospective review of the medical records. RESULTS The median age at diagnosis was 65 years (range, 40-85 years), and 34.4% of the patients presented with metastatic disease (stage M1). Of these patients, 56% had received definitive primary therapy, all had received androgen-deprivation therapy, and 52% had received docetaxel. The patients had received a median of 7 (1-14) systemic therapies before death. Most were secondary hormonal manipulations after the diagnosis of mCRPC (median, 4; range, 0-9). The median survival was 69 months (range, 5-270 months) after diagnosis, and the median age at death was 73 years (range, 47-95 years). The presence of metastases at diagnosis was a significant predictor of early death (hazard ratio, 4.33; P < .001), and definitive primary therapy was a significant predictor of longer survival (P < .001). The median survival for patients presenting with metastases was 39 months (range, 5-235 months) compared with 100 months (range, 6-270 months) for those with localized disease (P < .001). The median age at diagnosis between the docetaxel- and non-docetaxel-treated patients was significantly different at 62 and 71 years, respectively (P = .002). CONCLUSION The present retrospective analysis provides initial views clarifying the clinical characteristics of men dying of mCRPC and the therapies they received before death. Additional data are needed in multi-institutional settings to confirm these findings.

Laboratory‐Based Biomarkers and Liver Metastases in Metastatic Castration‐Resistant Prostate Cancer

BACKGROUND Metastatic castrate-resistant prostate cancer (mCRPC) patients with liver metastases have a poor prognosis. No large studies have investigated the clinical and biochemical parameters associated with liver metastases in this population. MATERIALS AND METHODS Patient data made available via Project Data Sphere were collected from 1,281 men with mCRPC who were enrolled on to three phase III clinical trials for the treatment of their disease. Multiple logistic regression was performed on eight clinical and biochemical baseline variables to test their association with the presence of liver metastases on baseline radiographic imaging. Variables of interest included prior docetaxel exposure, Eastern Cooperative Oncology Group performance status, albumin, alkaline phosphatase, alanine transaminase, aspartate transaminase (AST), hemoglobin (HGB), lactate dehydrogenase (LDH), prostate-specific antigen, and total bilirubin. Final models were compared when treating the variables as either continuous or categorized. RESULTS Multiple variable analysis demonstrated that an increasing serum AST or LDH or a decreasing HGB was associated with an increased probability of having documented radiographic liver metastases (p < .0001). The area under the curve for the continuous model was 0.6842 and 0.6890 for the categorical one, with the latter model containing a dichotomized AST and LDH based on the upper limit of normal and tertile ranges of HGB based on the distribution of the outcome. CONCLUSION Our analysis demonstrated a significant association between the presence of liver metastases and laboratory levels of AST, LDH, and HGB. These have implications for patient management. More research is needed to validate these biomarkers and prospectively determine their application in the clinical setting. IMPLICATIONS FOR PRACTICE The purpose of this study was to evaluate biochemical and clinical biomarkers associated with the presence of liver metastases in men diagnosed with metastatic castrate-resistant prostate cancer. The results indicate that quantitative assessments of aspartate transaminase, lactate dehydrogenase, and hemoglobin are significantly associated with an increased probability of having documented radiographic liver metastases. Analysis of these simple variables can alert clinicians to those at high risk for prostate cancer that has spread to the liver, a finding of clear importance for clinical management.

Clinical differences between African-Americans (AA) and Caucasians (CA) with and without family history (FH) of prostate cancer.

279 Background: Prostate cancer is one of the most common adult malignancies. Two well characterized risk factors for prostate cancer (PCa) are family history (FH) and race. The goal of this study was to distinguish the influence of family history and race with regards to clinically relevant covariates. Methods: In this single-institution study, 497 PCa patients from Tulane Hospital were clinically annotated and FH was evaluated. FH was defined as having ≥ 1 first degree relative affected with PCa and/or ≥ 2 affected second or third degree relatives. There were 147 AA and 350 CA patients; 66 AA and 120 CA reported PCa FH. The following clinical factors were documented: age and PSA at diagnosis (dx), Gleason score (biopsy or radical prostatectomy), and presence of metastasis (at any time). Chi-square, ANOVA, and odds ratio tests were performed to identify potential clinical correlates with regard to FH and race. Results: Results indicate that race and FH are not independent (p = 0.0266), where AAs were 1.5...