High neutrophil-to-lymphocyte ratio persistent during first-line chemotherapy predicts poor clinical outcome in patients with advanced urothelial cancer.

BACKGROUND: Increased neutrophil-to-lymphocyte ratio (NLR), an index of systemic inflammation, is associated with poor outcome for various types of cancers. We assessed the role on outcome prediction of NLR at baseline and persistent during first-line chemotherapy in patients with advanced urothelial cancer. METHODS: We retrospectively reviewed 292 patients with unresectable or metastatic urothelial cancer treated with first-line chemotherapy between January 2003 and December 2012. The cutoff values of NLR (>3 vs. <3) were evaluated before therapy and at day 1 of the second and third cycle (follow-up NLR). After univariate analysis, a multivariate analysis was carried out by Cox regression model and included the following variables: Eastern Cooperative Oncology Group (ECOG) performance status (≥ 2 vs. 0-1), visceral disease (present vs. absent), hemoglobin (<12 g/dL vs. >12 g/dL), pretherapy NLR (>3 vs. <3), and follow-up NLR (>3 vs. ≤ 3). RESULTS: Patients with pre- and follow-up NLR of >3 had a median progression-free survival of 3.2 months and a median overall survival of 5.7 months. In multivariate analysis, visceral metastases, pretherapy hemoglobin, and follow-up NLR were significant predictors of progression-free survival [hazard ratio (HR) 1.75, P = 0.0001; HR 1.57, P = 0.0015; HR 2.77, P < 0.0001, respectively], and of overall survival (HR 1.60, P = 0.0023; HR 1.59, P = 0.0024; HR 2.89, P < 0.0001, respectively); whereas pretherapy NLR remained as predictor of overall survival only (HR 1.53, P = 0.0101). CONCLUSIONS: An increased NLR persistent during first-line chemotherapy is an independent predictive factor for patients with advanced urothelial cancer.

Endometriosis and endometrial cancer: A propensity score-adjusted real-world data study.

Endometriosis is a benign condition characterized by the presence of ectopic endometrial tissue. Our study investigated the effect of endometriosis on the risk of endometrial cancer (EC) and the prognosis of endometriosis-associated EC. In our study, 197,196 patients with endometriosis and without a previous diagnosis of EC were compared with 6,455,556 females encountering health services for examinations, with body mass index (BMI) data, and without endometriosis or EC. A propensity score generated 197,141 matched pairs. In the endometriosis cohort, 875 cases of EC were seen, whereas 558 were in the control group: the hazard ratio (HR) was 1.56 (95% CI 1.40-1.73, p < 0.001). Women with endometriosis were more likely to develop invasive endometrioid (p = 0.005) and clear cell (p < 0.001) EC. There was no difference in overall survival between endometriosis-associated EC and EC without endometriosis. Our epidemiological findings were consistent with the evidence of an association between endometriosis and EC.

Vitamin D status among long-term survivors of testicular cancer.

A correlation between disturbances in hormone levels and the onset of metabolic disorders has been reported in long-term survivors of testicular cancer (TC).We evaluated serum vitamin D levels and other biological parameters in a consecutive series of 61 long-term (≥3 years) unilateral TC survivors with a median a follow-up of 4 years and in a cohort of healthy males. Deficient vitamin D levels were observed in 10 (17%) of the 58 long-term unilateral TC survivors but were not reported in healthy males (p=.019, Fisher test). Median vitamin D levels were 18.6 ug/L in 58 assessable TC survivors and 23.6 ug/L in 40 healthy males (p=.031). In univariate logistic regression analysis, TC diagnosis was associated with inadequate levels of vitamin D (p=.047). Vitamin D levels were lower when follow-up was > 10 years, albeit this difference was not statistically significant (p=.074). Long-term (especially > 10 years) TC survivors may have difficulty maintaining optimal vitamin D levels. Larger studies are needed to better characterize vitamin D status and possible correlations with premature hormonal aging reported in long-term TC survivors.

Conditional survival of patients treated with first-line chemotherapy for metastatic urothelial cancer.

BACKGROUND: Measures of prognosis for cancer patients are typically evaluated at the time of diagnosis. However, this study assessed the changes in 2-year CS rates after first-line chemotherapy for metastatic UC. PATIENTS AND METHODS: Conditional overall survival and CPFS probability were estimated using the Kaplan-Meier method. Adjusted survival functions were stratified according to age groups (< 70 years vs. ≥ 70 years), sex, Eastern Cooperative Oncology Group (ECOG) performance status (PS; ECOG PS ≤ 2 vs. ECOG PS > 2), pretreatment Hb levels (< 12 mg/dL vs. ≥ 12 mg/dL) and pretreatment NLR (< 3 vs. ≥ 3). Pairs of CS curves were compared using the Mantel-Haenszel log-rank test. RESULTS: Two hundred ninety-eight patients were included in this analysis, 233 were male, and their median age was 69 years. First-line median overall survival and progression-free survival were 10.7 months (95% confidence interval [CI], 9.6-12.6) and 6.0 months (95% CI, 5.5-7.1), respectively. CPFS and COS showed an increasing trend in the population considered (b = 0.35; P < .001 and b = 0.79; P < .001, respectively). A significant increase in terms of COS and CPFS trends was identified in patients with age < 70 years (P = .02 and P = .005, respectively) and pretreatment NLR ≤ 3 (P = .05 and P < .001, respectively). Patients with Hb levels < 12 g/dL showed a significantly poorer 2-year COS. CONCLUSION: The conditional probability of survival at 2 years from the start of first-line chemotherapy for advanced UC changes over time according to clinical characteristics.

PSA flare with abiraterone in patients with metastatic castration-resistant prostate cancer.

BACKGROUND: The aim of this study was to assess early serum prostate-specific antigen (PSA) changes in patients treated with abiraterone and to correlate those changes with clinical outcome. PATIENTS AND METHODS: We retrospectively evaluated 103 patients with castrate-resistant prostate cancer (CRPC) treated with compassionate use of abiraterone in Romagna, Italy. In these patients, serum PSA levels were monitored every 4 weeks, and a time course of serum PSA levels was obtained. The PSA flare phenomenon was evaluated. The log-rank test was applied to compare survival between groups of patients according to early PSA level changes. RESULTS: Of 103 patients, 43 (41.7%) had an immediate PSA response, whereas 9 (8.7%) had an initial PSA flare. Of the 9 patients with PSA flare, 5 attained a subsequent PSA response. The temporary PSA flare exceeded baseline values by a median of 19.7% (range, 5%-62.9%). The median PFS of the 9 patients in the PSA-flare group was higher compared with patients without the PSA flare (10.5 vs. 6.4 months; P = .0999) but was similar to the subgroup of patients with immediate PSA response (10.5 vs. 10.7 months; P = .7019). In the multivariate analysis, only the PSA response remained as a predictor of progression-free survival (PFS) (P < .0001) and overall survival (OS) (P = .0003), respectively. CONCLUSION: PSA flare occurs not infrequently in patients with CRPC who respond to abiraterone. Patients should be informed of this possible PSA flare phenomenon.

Early outcome prediction on 18F-fluorocholine PET/CT in metastatic castration-resistant prostate cancer patients treated with abiraterone.

OBJECTIVE: We investigated the role of 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) in the early evaluation of abiraterone and outcome prediction in patients with metastatic castration-resistant prostate cancer (CRPC). PATIENT AND METHODS: Forty-three patients with metastatic CRPC progressing after docetaxel received abiraterone 1,000 mg daily with prednisone 5 mg twice daily. Patients were evaluated monthly for serological PSA response and safety. FCH-PET/CT was done at baseline and after 3 to 6 weeks. Univariate and multivariate Cox regression models addressed potential predictors of progression-free survival (PFS) and overall survival (OS). RESULTS: Declines in PSA level of ≥50% were seen in 21 of 43 (49%) patients. Forty-two patients were evaluable for FCH-PET/CT response. FCH-PET/CT bone flare was observed in 4 of 42 (10%) evaluable patients. In univariate analysis, PSA decline and FCH-PET/CT response predicted PFS, while PSA decline and FCH-PET/CT (progression vs non progression) predicted OS. In multivariate analysis, only FCH-PET/CT (progression vs nonprogression) remained significant for PFS and OS (p = 0.022 and p = 0.027, respectively). CONCLUSION: Early FCH-PET/CT can predict clinical outcome in CRPC beyond PSA response. These data support further studies on FCH-PET/CT for abiraterone monitoring and outcome prediction in patients with CRPC.

Perspectives on mTOR inhibitors for castration-refractory prostate cancer.

The phosphatidylinositol 3'-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway contributes to prostate cancer progression and transition to androgen-independent disease. Furthermore, recent microarray analysis demonstrates that this pathway is often deregulated during prostate cancer progression. Thus, targeting of PI3K/AKT/mTOR may present a promising therapy for castration-refractory prostate cancer (CRPC). In recent years, several interesting strategies have been developed that interfere with distinct components of the PI3K/AKT/mTOR cascade. This article discusses many of the mechanisms involved, specifically in the context of prostate cancer. In addition, we present an overview of preliminary data on the activity of mTOR inhibitors and on the key steps to evaluate which of these compounds are most suitable for the treatment of prostate cancer. Particular emphasis is also placed on the development of novel perspectives to improve the poor prognosis of patients with CRPC.