Abstract 4962: Very-small-nuclear circulating tumor cell (vsnCTC) as a putative biomarker for visceral metastasis in metastatic castration-resistant prostate cancer (mCRPC)
Authors: Chen Jie-Fu , Ho Hao , Hodara Elisabeth , Ureno Alexander , Go Ann , Kaufman Elizabeth , Sievert Margarit , Luthringer Daniel J. , Huang Jiaoti , Chung Leland , Ke Zunfu , Li Ker-Chau , Tseng Hsian-Rong , Posadas Edwin M. 
Published: July 2016

Introduction and Objective: Patients with metastatic castration-resistant prostate cancer (mCRPC) who develop visceral metastases (VM) have poorer clinical outcomes in comparison to those without VM. Currently, VM are discovered late in the clinical course of mCRPC-VM and this aggressive natural history typically culminates in organ failure. There are no existing tests that identify men at risk for VM other than radiography. Our team performed circulating tumor cell (CTC) enumeration using NanoVelcro CTC Assay on prostate cancer patients across the spectrum of metastatic states: no metastasis, non-visceral metastasis, and VM. We identified an association between the presence of very-small-nuclear CTCs (vsnCTCs, DAPI+/Cytokeratin+/CD45- with nuclear size &lt; 8.5μm) and VM. Serial enumeration studies suggested the emergence of vsnCTCs occurred before the radiographic detection of VM, and the change of vsnCTC counts reflected the patients’ disease progression. We then hypothesized that presence of vsnCTC signals the presence of VM and has predictive and prognostic value with respect to VM.

Methods: We identified mCRPC patients who had progressed through next generation hormonal maneuvers such as abiraterone, enzalutamide, or an equivalent drug. Serial blood specimens were used for vsnCTC enumeration using NanoVelcro CTC Assay as previously published. The vsnCTC counts were related to the presence and development of VM (evaluated by radiography) as well as the response to anti-cancer treatment.

Results: Blood specimens were identified from 28 patients who met the eligibility criteria; 15/28 patients presented with VM and 13/28 had bone-only disease at their first CTC enumeration. Five out of 13 non-VM patients developed VM during follow-up, and vsnCTCs were detected 86-196 days prior to radiographic detection of VM (true positive); 4/13 had vsnCTCs detected but no VM was found by the time of analysis (false positive). None of the vsnCTC(-) patients developed VM. vsnCTCs were detected in 20/20 VM patients compared to 4/8 non-VM patients. Reduction of vsnCTC count occurred at initiation of anti-cancer treatment; transition from vsnCTC(-) to vsnCTC(+) was seen prior to progression under the treatment. Of the patients who have VM, 14 passed away at the time of this abstract submission including all the patients converting from non-VM to VM during the time of follow-up. Two out of 8 non-VM patients passed away including one patient who had vsnCTCs detected around 6 months prior to death.

Conclusions: vsnCTCs are associated with the presence of VM. The vsnCTC is a potential biomarker for predicting the development of VM and monitoring the treatment response in mCRPC. Transition from vsnCTC(-) to vsnCTC(+) was associated with the development of VM and progression under the treatment.

Citation Format: Jie-Fu Chen, Hao Ho, Elisabeth Hodara, Alexander Ureno, Ann Go, Elizabeth Kaufman, Margarit Sievert, Daniel J. Luthringer, Jiaoti Huang, Leland Chung, Zunfu Ke, Ker-Chau Li, Hsian-Rong Tseng, Edwin M. Posadas. Very-small-nuclear circulating tumor cell (vsnCTC) as a putative biomarker for visceral metastasis in metastatic castration-resistant prostate cancer (mCRPC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4962.