Association of aromatase with bladder cancer stage and long-term survival: new insights into the hormonal paradigm in bladder cancer

BACKGROUND Hormonal factors may play a role in bladder cancer (BCa). We investigated the expression of aromatase and estrogen receptor (ER)β and its association with pathological variables and survival outcomes. PATIENTS AND METHODS BCa specimens from 40 patients were evaluated. Immunohistochemistry was performed for aromatase and ERβ. Descriptive statistics and univariate analyses assessed the association of these markers with pathologic variables and survival outcomes. RESULTS Aromatase expression was significantly associated with tumor stage; muscle-invasive disease was found in 15 of 19 (79%) patients with positive staining and in 7 of 18 (39%) patients with negative staining (P = .02). Node-positive disease was found in 8 of 19 (42%) patients with positive staining and 1 of 18 (6%) patients with negative staining (P = .01). After a median follow-up of 112 months, Cox regression analysis demonstrated that aromatase expression was associated with a more than 2-fold risk of cancer recurrence (hazard ratio, 2.37; confidence interval, 0.92-6.08; P = .07) and an almost 4-fold higher risk of cancer-specific death (hazard ratio, 3.66; 95% confidence interval, 1.19-12.06; P = .02). Muscle-invasive disease was found in 15 of 18 (83%) ERβ-positive specimens and 4 of 12 (33%) ERβ-negative specimens (P = .0009). Hierarchical clustering analysis demonstrated a 4-fold up-regulation of ERβ gene expression in tumor versus adjacent, non-tumor urothelium (P < .05). However, no significant association with survival outcomes was found. CONCLUSION Aromatase expression in BCa may be associated with advanced tumor stage and poorer survival outcomes. ERβ is upregulated in malignant tissue, and its expression is associated with muscle-invasive disease. These findings provide further evidence for the hormonal paradigm in BCa

Racial Variation in the Utility of Urinary Biomarkers PCA3 and T2ERG in a Large Multicenter Study.

PURPOSE To our knowledge it is unknown whether urinary biomarkers for prostate cancer have added utility to clinical risk calculators in different racial groups. We examined the utility of urinary biomarkers added to clinical risk calculators for predicting prostate cancer in African American and nonAfrican American men. MATERIALS AND METHODS Demographics, PCPT (Prostate Cancer Prevention Trial) risk scores, data on the biomarkers data PCA3 (prostate cancer antigen 3) and T2ERG (transmembrane protease serine 2 and v-ets erythroblastosis virus E26 oncogene homolog gene fusion), and biopsy pathology features were prospectively collected on 718 men as part of EDRN (Early Detection Research Network). Utility was determined by generating ROC curves and comparing AUC values for the baseline multivariable PCPT model and for models containing biomarker scores. RESULTS PCA3 and T2ERG added utility for the prediction of prostate cancer and clinically significant prostate cancer when combined with the PCPT Risk Calculator. This utility was seen in nonAfrican American men only for PCA3 (AUC 0.64 increased to 0.75 for prostate cancer and to 0.69-0.77 for clinically significant prostate cancer, both p <0.001) and for T2ERG (AUC 0.64-0.74 for prostate cancer, p <0.001, and 0.69-0.73 for clinically significant prostate cancer, p = 0.029). African American men did not have an added benefit with the addition of biomarkers, including PCA3 (AUC 0.75-0.77, p = 0.64, and 0.65-0.66, p = 0.74) and T2ERG (AUC 0.75-0.74, p = 0.74, and 0.65-0.64, p = 0.88), for prostate cancer and clinically significant prostate cancer, respectively. Limitations include the small number of African American men (72). The post hoc subgroup analysis nature of the study limited findings to being hypothesis generating. CONCLUSIONS As novel biomarkers are discovered, clinical utility should be established across demographically diverse cohorts

Validation of risk factors for recurrence of renal cell carcinoma: Results from a large single-institution series

Purpose To validate prognostic factors and determine the impact of obesity, hypertension, smoking and diabetes mellitus (DM) on risk of recurrence after surgery in patients with localized renal cell carcinoma (RCC). Materials and methods We performed a retrospective cohort study among patients that underwent partial or radical nephrectomy at Weill Cornell Medicine for RCC and collected preoperative information on RCC risk factors, as well as pathological data. Cases were reviewed for radiographic evidence of RCC recurrence. A Cox proportional-hazards model was developed to determine the contribution of RCC risk factors to recurrence risk. Disease-free survival and overall survival were analyzed using the Kaplan-Meier method and log-rank test. Results We identified 873 patients who underwent surgery for RCC between the years 2000–2015. In total 115 patients (13.2%) experienced a disease recurrence after a median follow up of 4.9 years. In multivariate analysis, increasing pathological T-stage (HR 1.429, 95% CI 1.265–1.614) and Nuclear grade (HR 2.376, 95% CI 1.734–3.255) were independently associated with RCC recurrence. In patients with T1-2 tumors, DM was identified as an additional independent risk factor for RCC recurrence (HR 2.744, 95% CI 1.343–5.605). Patients with DM had a significantly shorter median disease-free survival (1.5 years versus 2.6 years, p = 0.004), as well as median overall survival (4.1 years, versus 5.8 years, p<0.001). Conclusions We validated high pathological T-stage and nuclear grade as independent risk factors for RCC recurrence following nephrectomy. DM is associated with an increased risk of recurrence among patients with early stage disease