The heterogeneity of an individual patient's tumor has been linked to treatment resistance, but quantitative biomarkers to rapidly and reproducibly evaluate heterogeneity in a clinical setting are currently lacking. Using established tools available in a CAP-accredited and CLIA-certified clinical laboratory, we quantified digital pathology features on 9,225 individual circulating tumor cells (CTCs) from 179 unique metastatic castration-resistant prostate cancer (mCRPC) patients to define phenotypically distinct cell types. Heterogeneity was quantified based on the diversity of cell types in individual patient samples using the Shannon index and associated with overall survival (OS) in the 145 specimens collected prior to initiation of second or later lines of therapy. Low CTC phenotypic heterogeneity was associated with better OS in patients treated with androgen receptor signaling inhibitors (ARSI), whereas high heterogeneity was associated with better OS in patients treated with taxane chemotherapy. Overall, the results show that quantifying CTC phenotypic heterogeneity can help inform the choice between ARSI and taxanes in mCRPC patients.
Cancer research. 2017 Aug 17 [Epub ahead of print]
Howard I Scher, Ryon P Graf, Nicole Schreiber, Brigit McLaughlin, Adam Jendrisak, Yipeng Wang, Jerry Lee, Stephanie Greene, Rachel Krupa, David Lu, Pascal Bamford, Jessica Louw, Lyndsey Dugan, Hebert Alberto Vargas, Martin Fleisher, Mark Landers, Glenn Heller, Ryan V Dittamore
Medicine(Genitourinary Oncology Service), Memorial Sloan-Kettering Cancer Center ., Epic Sciences., Medicine(Genitourinary Oncology Service), Memorial Sloan-Kettering Cancer Center., Medicine, Memorial Sloan Kettering Cancer Center., Epic Sciences, Epic Sciences., Department of Radiology, Memorial Sloan Kettering Cancer Center., Laboratory Medicine, Memorial Sloan-Kettering Cancer Center., Translational Research, Epic Sciences., Biostatics, Memorial Sloan-Kettering Cancer Center.