Nicholas J Vogelzang1, Karim Fizazi2, John M Burke3, Ronald De Wit4, Joaquim Bellmunt5, Thomas E Hutson6, Edward Crane7, William R Berry8, Kevin Doner9, John D Hainsworth10, Pawel J Wiechno11, Kejian Liu12, Michelle F Waldman12, Anita Gandhi12, Debora Barton12, Ulf Jungnelius12, Abderrahim Fandi12, Cora N Sternberg13, Daniel P Petrylak14. 1. US Oncology Research, Houston, TX, USA; Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA. Electronic address: Nicholas.Vogelzang@usoncology.com. 2. Institut Gustave Roussy, Department of Cancer Medicine, University of Paris Sud, Villejuif, France. 3. US Oncology Research, Houston, TX, USA; Rocky Mountain Cancer Centers, Aurora, CO, USA. 4. Erasmus MC Cancer Institute, Rotterdam, The Netherlands. 5. University Hospital del Mar-IMIM, Barcelona, Spain; Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. 6. Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas, TX, USA. 7. Oncology Hematology Care, Inc., Cincinnati, OH, USA. 8. US Oncology, Cancer Centers of North Carolina, Raleigh, NC, USA. 9. Texas Oncology, Austin, TX, USA. 10. Sarah Cannon Research Institute, Nashville, TN, USA. 11. Department of Uro-Oncology, Centrum Onkologii - Instytut im Marii Sklodowskiej-Curie, Warsaw, Poland. 12. Celgene Corporation, Summit, NJ, USA. 13. San Camillo and Forlanini Hospitals, Department of Medical Oncology, Rome, Italy. 14. Yale Cancer Center, Department of Medicine Division of Oncology, New Haven, CT, USA.
Abstract
Elevated circulating tumor cell (CTC) blood levels (≥5 cells/7.5ml) convey a negative prognosis in metastatic castration-resistant prostate cancer but their prognostic significance in patients receiving chemotherapy is uncertain. The association between CTC counts (at baseline or after treatment), overall survival (OS), and response to docetaxel with lenalidomide was evaluated in a 208-patient subset from the MAINSAIL trial, which compared docetaxel-prednisone-lenalidomide and docetaxel-prednisone-placebo in metastatic castration-resistant prostate cancer patients. Baseline CTCs were <5 cells/7.5ml bloodin 87 (42%) patients and ≥5 cells/7.5ml in 121 (58%) patients. Neither tumor response nor prostate-specific antigen response correlated with baseline CTCs. However, CTC count ≥5 cells/7.5ml was significantly associated with lower OS (hazard ratio: 3.23, p = 0.0028). Increases in CTCs from <5 cells/7.5ml to ≥5 cells/7.5ml after three cycles were associated with significantly shorter OS (hazard ratio: 5.24, p=0.025), whereas CTC reductions from ≥5 cells/7.5ml to <5 cells/7.5ml were associated with the best prognosis (p=0.003). PATIENT SUMMARY: Our study in metastatic castration-resistant prostate cancer patients treated withdocetaxel chemotherapy, with or without lenalidomide, showed that patient survival was best predicted by circulating tumor cell count at the start of treatment. A rising circulating tumor cell count after three cycles of therapy predicted poor survival, while a decline predicted good survival.
RCT Entities:
Elevated circulating tumor cell (CTC) blood levels (≥5 cells/7.5ml) convey a negative prognosis in metastatic castration-resistant prostate cancer but their prognostic significance in patients receiving chemotherapy is uncertain. The association between CTC counts (at baseline or after treatment), overall survival (OS), and response to docetaxel with lenalidomide was evaluated in a 208-patient subset from the MAINSAIL trial, which compared docetaxel-prednisone-lenalidomide and docetaxel-prednisone-placebo in metastatic castration-resistant prostate cancerpatients. Baseline CTCs were <5 cells/7.5ml blood in 87 (42%) patients and ≥5 cells/7.5ml in 121 (58%) patients. Neither tumor response nor prostate-specific antigen response correlated with baseline CTCs. However, CTC count ≥5 cells/7.5ml was significantly associated with lower OS (hazard ratio: 3.23, p = 0.0028). Increases in CTCs from <5 cells/7.5ml to ≥5 cells/7.5ml after three cycles were associated with significantly shorter OS (hazard ratio: 5.24, p=0.025), whereas CTC reductions from ≥5 cells/7.5ml to <5 cells/7.5ml were associated with the best prognosis (p=0.003). PATIENT SUMMARY: Our study in metastatic castration-resistant prostate cancerpatients treated with docetaxel chemotherapy, with or without lenalidomide, showed that patient survival was best predicted by circulating tumor cell count at the start of treatment. A rising circulating tumor cell count after three cycles of therapy predicted poor survival, while a decline predicted good survival.
Authors: Udit Singhal; Yugang Wang; James Henderson; Yashar S Niknafs; Yuanyuan Qiao; Amy Gursky; Alexander Zaslavsky; Jae-Seung Chung; David C Smith; R Jeffrey Karnes; S Laura Chang; Felix Y Feng; Ganesh S Palapattu; Russell S Taichman; Arul M Chinnaiyan; Scott A Tomlins; Todd M Morgan Journal: Mol Cancer Res Date: 2018-02-16 Impact factor: 5.852
Authors: Yoon Seok Suh; Jae Young Joung; Sung Han Kim; Ho Kyung Seo; Jinsoo Chung; Kang Hyun Lee Journal: Biomed Res Int Date: 2017-11-05 Impact factor: 3.411
Authors: Rebeca Lozano; David Lorente; Isabel M Aragon; Nuria Romero-Laorden; Paz Nombela; Joaquim Mateo; Alison H M Reid; Ylenia Cendón; Diletta Bianchini; Casilda Llacer; Shahneen K Sandhu; Adam Sharp; Pasquale Rescigno; Teresa Garcés; Maria I Pacheco; Penelope Flohr; Christophe Massard; Pedro P López-Casas; Elena Castro; Johann S de Bono; David Olmos Journal: Cancers (Basel) Date: 2021-05-12 Impact factor: 6.639