Association of persistent, unexplained leukocytosis, a paraneoplastic syndrome, with poor prognosis in patients with urothelial carcinoma of the bladder.

Abstract

291 Background: Unexplained leukocytosis, thought to be associated with paraneoplastic GCSF, has been described in several malignancies and is linked to a poor prognosis. We sought to define the disease characteristics and outcomes of those patients presenting with urothelial carcinoma and a persistently elevated WBC. Methods: We queried a prospectively maintained database at the University of Washington. Patients were included if they had a histological diagnosis of urothelial carcinoma of the bladder and a WBC of >20 x 103cells/µl. Patient charts were reviewed and were excluded from analysis if the leukocytosis was not persistent in duration or if an underlying cause for the leukocystosis could be identified. Clinical, histological and laboratory data were then collected from the remaining patient cohort. Results: We identified a total of 44 patients who met the inclusion criteria of having urothelial carcinoma of the bladder with a WBC of >20 x 103cells/µl. Of these patients, 7 (16%) patients with a median age of 61.9 (range 34 - 80) yrs at diagnosis had persistent, unexplained leukocytosis. Mixed histologies were present in 3 patients (extensive squamous differentiation in 2 and sarcomatoid differentiation in 1). At the time of presentation with leukocytosis, 5 of 7 had muscle invasive disease and 3 had evidence of metastatic disease. Leukocytosis was frequently associated with hypercalcemia (n = 5), thrombocytosis (n = 5) and anemia (n = 6). All patients died from their disease with the exception of one who is currently alive with locally advanced and unresectable disease 8 months after presentation. Median time from leukocytosis until death was 55 (range 8 - 139) days. Chemotherapy was able to achieve a WBC response in 2 of 4 patients although neither demonstrated a substantial reduction in tumor volume. Both patients ultimately developed a recurrence of their leukocytosis after chemotherapy and progression of their disease. Conclusions: The presence of leukocytosis conveys a poor prognosis. To our knowledge this represents the largest case series of patients with paraneoplastic leukocytosis secondary to urothelial carcinoma.