Genomic Correlates of Prostate-Specific Membrane Antigen Expression and Response to 177Lu-PSMA-617: A Retrospective Multicenter Cohort Study.

PURPOSE: While 177Lu-PSMA-617 (LuPSMA) is an effective therapy for many patients with metastatic castration-resistant prostate cancer (mCRPC), biomarkers associated with outcomes are not well defined. We hypothesized that prostate cancer mutational profile may associate with clinical activity of LuPSMA. We devised a study to evaluate associations between mCRPC mutational profile with LuPSMA clinical outcomes. METHODS: This was a multicenter retrospective analysis of patients with mCRPC with next-generation sequencing (NGS) who received LuPSMA. PSA50 response (ie, ≥50% decline in prostate-specific antigen [PSA]) rate, PSA progression free survival (PSA PFS), and overall survival (OS) were compared between genetically defined subgroups. RESULTS: One hundred twenty-six patients with NGS results who received at least one cycle of LuPSMA were identified. The median age was 73 (IQR, 68-78) years, 124 (98.4%) received ≥1 prior androgen receptor-signaling inhibitor, and 121 (96%) received ≥1 taxane-based chemotherapy regimen. Fifty-eight (46%) patients with a DNA damage repair gene mutation (DNA damage response group) and 59 (46.8%) with a mutation in TP53, RB1, or PTEN tumor suppressor genes (TSG group) were identified. After adjusting for relevant confounders, the presence of ≥1 TSG mutation was associated with shorter PSA PFS (hazard ratio [HR], 1.93 [95% CI, 1.05 to 3.54]; P = .034) and OS (HR, 2.65 [95% CI, 1.15 to 6.11]; P = .023). There was improved OS favoring the DNA damage response group (HR, 0.37 [95% CI, 0.14 to 0.97]; P = .044) on multivariable analysis. Univariate analysis of patients with ATM mutations had significantly higher rates of PSA50 response, PSA PFS, and OS. CONCLUSION: Outcomes on LuPSMA varied on the basis of mutational profile. Prospective studies to define the clinical activity of LuPSMA in predefined genomic subgroups are justified.

Comparative effectiveness of pelvic arterial embolization versus laparotomy in adults with pelvic injuries: A National Trauma Data Bank analysis.

PURPOSE: To compare the clinical outcomes and trends of arterial embolization (AE) versus laparotomy which are used in the management of pelvic trauma. MATERIALS AND METHODS: Adult patients with pelvic injuries were identified using the National Trauma Data Bank (NTDB) from 2007 to 2015. Patients with non-pelvic life-threatening injuries were excluded. Patients were grouped in operatively managed pelvic ring injuries, laparotomy ± fixation, AE ± fixation, and laparotomy and AE ± fixation. Using a linear mixed regression and logistic regression models, hospital length of stay (LOS), ICU days, ventilator days, and mortality for different therapies were compared. A propensity score weighting method was used to further eliminate treatment selection bias in the study sample and compare the outcomes between AE and laparotomy. RESULTS: Of 7473 pelvic trauma patients, 1226 (16.4%) patients were only operatively managed. 3730 patients (49.9%) underwent laparotomy, 2136 underwent AE (28.6%), and 381 (5.1%) patients underwent both laparotomy and AE. The year of injury, patient age, gender, race, severity of injury and presence of shock were found to be predictors of receipt of different therapies (P < 0.001 for all). When correcting for these confounding factors, the mortality rate was lower in the AE group compared to the laparotomy group 6.6% vs. 20.6% (P < 0.001). Additionally, LOS and ICU days were shorter for the AE group than the laparotomy group (P < 0.001). CONCLUSION: AE in patients with pelvic injuries is associated with lower mortality, as well as shorter LOS and ICU stays compared to laparotomy.