BACKGROUND:The prevalence of chronic kidney disease (CKD) in patients with upper tract urothelial carcinoma (UTUC) is poorly defined, both before and after nephrouretectomy. Although multimodal treatment paradigms for UTUC are under‐developed, this has important implications on patients' ability to receive cisplatin‐based combination chemotherapy (CBCC).METHODS:Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease formula in 336 patients with UTUC, who were treated at the Cleveland Clinic by nephroureterectomy since 1992. An eGFR cutoff of 60 mL/min/1.73 m2 was used to determine the presence of CKD and eligibility for CBCC.RESULTS:Median age was 72 years and median preoperative eGFR was 59 mL/min/1.73m2. Before nephroureterectomy, only 48% of patients were eligible to receive CBCC and this decreased to 22% postoperatively (P < .001). In the 144 patients with pT2‐pT4 and/or pN1‐pN3 disease who are suitable to receive CBCC, these proportions were 40% and 24%, respectively (P = .009). Although 50 patients overall received some form of perioperative chemotherapy, only 3 and 11 patients received neoadjuvant and adjuvant CBCC, respectively.CONCLUSIONS:CKD is prevalent in the UTUC population and a minority of patients has an optimal eGFR to receive neoadjuvant CBCC. Nephrouretectomy may eliminate CBCC as a therapeutic option in 49% of high‐risk patients if it is deferred to the adjuvant setting. Multimodal treatment strategies for UTUC should focus on neoadjuvant chemotherapy, as few patients are eligible for adjuvant CBCC because of the substantial decline in eGFR caused by nephroureterectomy. Cancer 2010. © 2010 American Cancer Society.

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Circulating tumor cells (CTCs) are associated with cancer progression, aggressiveness and metastasis. However, the frequency and predictive value of CTCs in patients remains unknown. If circulating cells are involved in tumor aggressiveness and metastasis, then cell levels should decline upon tumor removal in localized cancer patients, but remain high in metastatic patients. Accordingly, proposed biomarkers CD117/c-kit, CD133, CXCR4/CD184, and CD34-positive cell percentages in the blood of patients undergoing radical prostatectomy for localized cancer were assessed by flow cytometry prior to intervention and 1–3 months postoperatively. Only circulating CD117+ cell percentages decreased after radical prostatectomy, increased with cancer progression and correlated with high PSA values. Notably, postoperative CD117+ levels did not decrease in patients experiencing biochemical recurrence. In a xenograft model, CD117-enriched tumors were more vascularized and aggressive. Thus, CD117 expression on CTCs promotes tumor progression and could be a biomarker for prostate cancer diagnosis, prognosis, and/or response to therapy.

To survive and metastasize, tumors interact with surrounding tissues by secreting growth factors and cytokines. In return, surrounding host tissues respond by changing their secretome. Numerous factors theoretically function as therapeutic targets or biomarkers of cancer growth and metastatic risk. However, it is unclear if these factors are tumor-derived or actually represent the host defense. To analyze the concentrations of tumor- and microenvironment-derived factors associated with neoplastic growth, we used ELISA-based arrays specific for murine or human proteins to establish a profile of tumor- or host-derived factors circulating in the plasma or within the platelets upon human tumor implantation into mice. Many factors characterized as tumor-derived were actually secreted by host tissues. This study uncovered the origin of various cytokines and revealed their circulation methods. We found that tumor-produced cytokines are predominantly sequestered in platelets. Sequestered proteins are protected from degradation and, thus, may be functional at metastatic sites. These findings identify tumor-specific targets for the detection and prevention of tumor growth and metastasis. As predicted by our model, monocyte chemotactic protein 1 and tumor necrosis factor alpha may be biomarkers for human cancers. Thus, our study identified several potential biomarkers that might be predictive of prostate cancer.