Abstract 379: Circulating tumor cells (CTCs) in clinically localized prostate cancer (PCa): searching a prognostic tool
Authors: Rossi Elisabetta , Facchinetti Antonella , Aneloni Vittorio , Zilio Emanuel , Dal Bianco Massimo , Zoccoli Alice , Santini Daniele , Garrou Diletta , Porpiglia Francesco , Zamarchi Rita 
Published: August 2015

Abstract
Background
If PCa screening has reduced advanced disease and disease-specific mortality, the tradeoff is an over-diagnosis of cases that would not have caused clinical consequences during a man's lifetime if left untreated. Conversely, a vast numbers of men, which harbor occult extra-prostatic extension, develop recurrence after surgery.
Despite it looks like an addressable question by quantifying Circulating Tumor Cells (CTCs), unlike breast cancer, in which prognostic and predictive impact of tumor cells in peripheral blood or bone marrow (Disseminated Tumor Cells, DTCs) was largely provided, their role in localized PCa is far from clear.
Methods
From July 2011 to August 2013, we quantify the tumor burden at diagnosis in peripheral blood of 153 PCa patients stage T2a-T3b, enrolled at three clinical sites (Roma, Orbassano and Padova). All the patients were candidate to undergo radical prostatectomy because of positive biopsy for cancer. Two labs (Orbassano and Padova) performed the CellSearch assay.
In patients enrolled in Roma (Janus trial, a phase II study for the use of zoledronic acid as neoadjuvant treatment of invasive PCa), we evaluated in parallel the DTCs.
Results
We used data obtained in patients enrolled in Orbassano (n = 50) and Roma (n = 15) as training set, meanwhile we used patients of Padova (n = 88) as validation set. Consistently with previous reports (Kraan, Sleijfer et al. 2011) reporting low inter-test and inter-lab variability, the baseline CTC count in the two sets did not significantly differ (Mann-Whitney Rank Sum Test, p = 0.170), so that they were further analyzed altogether.
Overall, we found that 74 out of 153 PC patients (48,4%) had at least 1 CTC per 7.5 ml of peripheral blood; 45 PC (29,4%) patients had &gt; 2 cells and 21 PC patients (13,7%) had &gt; 3 cells. Interestingly, 8 out of 153 PC patients (5,2%) had &gt; 5 cells at the first blood draw, before surgery.
When we synchronously detected CTCs and DTCs, we found consistent results in 64% of patients (Wilcoxon signed Rank Test, p = 0.339).
Conclusions
Even when the PCa is pathologically organ confined at surgery, it was reported 5% to 20% of these patients harbor foci of micro-metastatic disease that will later manifest itself as recurrent disease. Here we show CTCs by CellSearch assay in close to 50% of biopsy-confirmed PCa patients, obtaining evidence of a systemic disease.
Prospective studies will be required to investigate whether CTC-status is associated with worst outcome in the M0 setting of PCa, as already provided in early breast cancer patients (Lucci, Hall et al. 2012).
Citation Format: Elisabetta Rossi, Antonella Facchinetti, Vittorio Aneloni, Emanuel Zilio, Massimo Dal Bianco, Alice Zoccoli, Daniele Santini, Diletta Garrou, Francesco Porpiglia, Rita Zamarchi. Circulating tumor cells (CTCs) in clinically localized prostate cancer (PCa): searching a prognostic tool. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 379. doi:10.1158/1538-7445.AM2015-379