BACKGROUND: Carcinomas of the upper urinary tract are uncommon tumors that usually occurred in elderly patients. Competing causes of mortality should be considered when treating these patients.METHODS: All patients with upper urinary tract tumors who were treated surgically at Centre Hospitalier Universitaire de Québec and affiliated hospitals from 1978 to 2001 were retrospectively reviewed. Clinical and pathologic variables were assessed from both the preoperative and postoperative periods of management, and clinical outcomes were tracked. Competing risks regression, Cox proportional hazards modeling, and multiple imputation were used to assess predictors of cancer‐related and competing risks‒related mortality in both preoperative and postoperative settings.RESULTS: Competing risks were responsible for 46% of deaths in this cohort of 168 patients. Preoperatively, the most important predictor of cancer‐related mortality was a clinically invasive tumor (hazards ratio [HR], 3.97; P < .001), whereas increasing age (HR, 1.07; P < .001) was found to be the most important predictor of competing mortality. Postoperatively, tumor grade was the most important predictor of cancer‐related mortality (HR, 3.92; P < .001) whereas constitutional symptoms (HR, 1.91; P = .015) and increasing age (HR, 1.06; P < .001) were found to be predictive of competing mortality.CONCLUSIONS: In the current study, stage and grade were found to be the 2 most important independent predictors of survival in patients with tumors of the upper urinary tract and were highly correlated. Pain or weight loss was found to be a novel predictor of survival in this cancer. Although a survival disadvantage was not noted for women, nephron‐sparing surgery, ureteral tumors, or older patients with respect to cancer, competing causes of mortality were found to be responsible for greater than one‐third of observed deaths and age was the best predictor of this occurrence. Cancer 2009. © 2009 American Cancer Society.

The role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in prostate cancer (PCa) has not been well defined yet. Because high-grade PCa tends to exhibit increased glycolytic rate, FDG-PET/CT could be useful in this setting. The aim of this study was to assess the value of FDG-PET/CT for pre-operative staging and prognostic stratification of patients with high-grade PCa at biopsy. Fifty-four patients with a Gleason sum ≥8 PCa at biopsy underwent FDG-PET/CT as part of the staging workup. Thirty-nine patients underwent radical prostatectomy (RP) and pelvic lymph node (LN) dissection, 2 underwent LN dissection only, and 13 underwent non-surgical treatments. FDG-PET/CT findings from clinical reports, blinded reading and quantitative analysis were correlated with clinico-pathological characteristics at RP. Suspicious foci of increased FDG uptake were found in the prostate, LNs and bones in 44, 13 and 6% of patients, respectively. Higher clinical stage, post-RP Gleason sum and pattern, and percentage of cancer involvement within the prostate were significantly associated with the presence of intraprostatic FDG uptake (IPFU) (P < 0.05 in all cases). Patients without IPFU who underwent RP were downgraded to Gleason ≤7 in 84.6% of cases, as compared to 30.8% when IPFU was reported (P = 0.003). Qualitative and quantitative IPFU were significantly positively correlated with post-RP Gleason pattern and sum, and pathological T stage. Absence and presence of IPFU were associated with a median 5-year cancer-free survival probability of 70.2 and 26.9% (P = 0.0097), respectively, using the CAPRA-S prognostic tool. These results suggest that, among patients with a high-grade PCa at biopsy, FDG-PET/CT could improve pre-treatment prognostic stratification by predicting primary PCa pathological grade and survival probability following RP.

Tissue factor (TF), a transmembrane glycoprotein responsible for initiating the extrinsic pathway of blood coagulation plays a key role in cancer growth, metastasis and angiogenesis. Various studies have demonstrated the prognostic potential of TF expression in several cancers. However, its role in bladder cancer is unclear. This study evaluated the prognostic potential of TF expression in muscle‐invasive bladder tumors from patients treated with radical cystectomies. Immunohistochemical staining using a monoclonal antibody (mAb) anti‐TF was carried out on sections of tissue microarray blocks containing cores of muscle‐invasive bladder tumors (4 cores/tumor) from 218 patients. The intensity of the staining was evaluated on a scale from 0 to 3 by two independent observers who were both unaware of the clinicopathological characteristics of the samples. TF was expressed in 77.6% of tumors, independently from baseline characteristics (age, gender, stage and grade) as assessed using the χ² and Student t tests. During follow‐up (median: 2.6 years), 45.4% of the patients died from the progression of their cancer. Kaplan–Meier survival showed that among the 103 patients with node‐negative (N0) transitional cell carcinoma (TCC), those with TF‐positive tumors had shorter bladder cancer‐specific survival (p = 0.0276). Moreover, multivariate Cox regression analysis showed they had a 3.15‐fold greater risk of dying from bladder cancer (95% CI: 1.1–9.0; p = 0.032). In conclusion, TF expression was an independent predictor of disease‐specific survival in N0 muscle‐invasive TCCs treated by radical cystectomy and therefore, might help identify patients at higher risk of disease progression. These patients could potentially benefit from adjuvant chemotherapy.

Just like the androgen receptor (AR), the estrogen receptor α (ERα) is expressed in the prostate and is thought to influence prostate cancer (PCa) biology. Yet the incomplete understanding of ERα functions in PCa hinders our ability to fully comprehend its clinical relevance and restricts the repurposing of estrogen-targeted therapies for the treatment of this disease. Using 2 human PCa tissue microarray cohorts, we first demonstrate that nuclear ERα expression was heterogeneous among patients, being detected in only half of the tumors. Positive nuclear ERα levels were correlated with disease recurrence, progression to metastatic PCa, and patient survival. Using in vitro and in vivo models of the normal prostate and PCa, bulk and single-cell RNA-Seq analyses revealed that estrogens partially mimicked the androgen transcriptional response and activated specific biological pathways linked to proliferation and metabolism. Bioenergetic flux assays and metabolomics confirmed the regulation of cancer metabolism by estrogens, supporting proliferation. Using cancer cell lines and patient-derived organoids, selective estrogen receptor modulators, a pure anti-estrogen, and genetic approaches impaired cancer cell proliferation and growth in an ERα-dependent manner. Overall, our study revealed that, when expressed, ERα functionally reprogrammed PCa metabolism, was associated with disease progression, and could be targeted for therapeutic purposes.