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BackgroundLoss of the tumor suppressor phosphatase and tensin homolog (PTEN) occurs frequently in prostate cancers. Preclinical evidence suggests that activation of PI3K/AKT signaling through loss of PTEN can result in resistance to hormonal treatment in prostate cancer.ObjectiveTo explore the antitumor activity of abiraterone acetate (abiraterone) in castration-resistant prostate cancer (CRPC) patients with and without loss of PTEN protein expression.Design, setting, and participantsWe retrospectively identified patients who had received abiraterone and had hormone-sensitive prostate cancer (HSPC) and/or CRPC tissue available for PTEN immunohistochemical analysis.Outcome measurements and statistical analysisThe primary end point was overall survival from initiation of abiraterone treatment. Relationship with outcome was analyzed using multivariate Cox regression and log-rank analyses.Results and limitationsA total of 144 patients were identified who had received abiraterone post-docetaxel and had available tumor tissue. Overall, loss of PTEN expression was observed in 40% of patients. Matched HSPC and CRPC tumor biopsies were available for 41 patients. PTEN status in CRPC correlated with HSPC in 86% of cases. Loss of PTEN expression was associated with shorter median overall survival (14 vs 21 mo; hazard ratio [HR]: 1.75; 95% confidence interval [CI], 1.19–2.55; p = 0.004) and shorter median duration of abiraterone treatment (24 vs 28 wk; HR: 1.6; 95% CI, 1.12–2.28; p = 0.009). PTEN protein loss, high lactate dehydrogenase, and the presence of visceral metastases were identified as independent prognostic factors in multivariate analysis.ConclusionsOur results indicate that loss of PTEN expression was associated with worse survival and shorter time on abiraterone treatment. Further studies in larger and prospective cohorts are warranted.Patient summaryPTEN is a protein often lost in prostate cancer cells. In this study we evaluated if prostate cancers that lack this protein respond differently to treatment with abiraterone acetate. We demonstrated that the survival of patients with loss of PTEN is shorter than patients with normal PTEN expression.

The current definition of plasma cell leukemia (PCL)— ≥ 20% circulating plasma cells (CPCs) on peripheral smear and plasma cell count ≥ 2 × 109/L—may be too stringent. We reviewed outcomes of 176 multiple myeloma (MM) patients diagnosed between 1971 and 2016, and who had CPCs detectable at diagnosis, to determine whether a lower threshold could be used to diagnose PCL. Median overall survival (mOS) was 1.1 years (95% CI 0.8–1.4) and was similar between patients with < 5% (n = 54, mOS = 1.4 years [0.7–2.0]), 5–19% (n = 63, mOS = 1.1 years [0.7–1.4]), and ≥ 20% CPCs (n = 59, mOS = 1.1 years [0.7–1.5], p = 0.349). As survival was similar between those with 5–19% and ≥ 20% CPCs, we stratified patients by < 5% (mOS = 1.4 years [0.7–2.0]) and ≥ 5% CPCs (mOS = 1.1 years [0.8–1.4], p = 0.154). Outcomes of those with ≥ 5% CPCs were much poorer when compared with a cohort of MM patients diagnosed between 1971 and 2016, who did not have CPCs at diagnosis (n = 9724, mOS = 4.4 yrs [4.3–4.5], p < 0.001); survival was also lower in patients diagnosed after 2001 with ≥ 5% CPCs (n = 62, mOS = 1.4 years [0.8–2.5]) compared with patients with standard risk (n = 1326, mOS = 7.5 years [7.0–8.7]) and high-risk MM (n = 381, mOS = 4.3 years [3.5–4.9], p < 0.001). We therefore propose that the definition of PCL be revised to patients with ≥ 5% CPCs on peripheral blood smear, who otherwise meet diagnostic criteria for MM.

Rationale. Pneumonia is a leading cause of postoperative complication. Objective. To examine trends, factors, and mortality of postoperative pneumonia following major cancer surgery (MCS). Methods. From 1999 to 2009, patients undergoing major forms of MCS were identified using the Nationwide Inpatient Sample (NIS), a Healthcare Cost and Utilization Project (HCUP) subset, resulting in weighted 2,508,916 patients. Measurements. Determinants were examined using logistic regression analysis adjusted for clustering using generalized estimating equations. Results. From 1999 to 2009, 87,867 patients experienced pneumonia following MCS and prevalence increased by 29.7%. The estimated annual percent change (EAPC) of mortality after MCS was −2.4% (95% CI: −2.9 to −2.0, P < 0.001); the EAPC of mortality associated with pneumonia after MCS was −2.2% (95% CI: −3.6 to 0.9, P = 0.01). Characteristics associated with higher odds of pneumonia included older age, male, comorbidities, nonprivate insurance, lower income, hospital volume, urban, Northeast region, and nonteaching status. Pneumonia conferred a 6.3-fold higher odd of mortality. Conclusions. Increasing prevalence of pneumonia after MCS, associated with stable mortality rates, may result from either increased diagnosis or more stringent coding. We identified characteristics associated with pneumonia after MCS which could help identify at-risk patients in order to reduce pneumonia after MCS, as it greatly increases the odds of mortality.