Value of Early Circulating Tumor Cells Dynamics to Estimate Docetaxel Benefit in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients
Por:
Lozano R, Lorente D, Aragon I, Romero-Laorden N, Nombela P, Mateo J, Reid A, Cendon Y, Bianchini D, Llacer C, Sandhu S, Sharp A, Rescigno P, Garces T, Pacheco M, Flohr P, Massard C, Lopez-Casas P, Castro E, de Bono J, Olmos D
Publicada:
1 may 2021
Resumen:
Simple Summary
The prognostic role of CTC enumeration in mCRPC patients has been established in several studies, demonstrating a higher prognostic performance than post-treatment changes in PSA levels in patients treated with AR signaling inhibitors, but not taxanes. We carried out a pooled analysis of two prospective studies in mCRPC patients treated with docetaxel. The results of this study showed a greater ability of early changes in circulating tumor cells (CTCs) compared to PSA response endpoints to predict overall survival in metastatic castration-resistant prostate cancer (mCRPC) patients treated with docetaxel. These results encourage the clinical usefulness of CTC enumeration to determine the outcome of mCRPC patients.
Circulating tumor cell (CTC) enumeration and changes following treatment have been demonstrated to be superior to PSA response in determining mCRPC outcome in patients receiving AR signaling inhibitors but not taxanes. We carried out a pooled analysis of two prospective studies in mCRPC patients treated with docetaxel. CTCs were measured at baseline and 3-6 weeks post treatment initiation. Cox regression models were constructed to compare 6-month radiographical progression-free survival (rPFS), CTCs and PSA changes predicting outcome. Among the subjects, 80 and 52 patients had evaluable baseline and post-treatment CTC counts, respectively. A significant association of higher baseline CTC count with worse overall survival (OS), PFS and time to PSA progression (TTPP) was observed. While CTC response at 3-6 weeks (CTC conversion (from >= 5 to <5 CTCs), CTC30 (>= 30% decline in CTC) or CTC0 (decline to 0 CTC)) and 6-month rPFS were significantly associated with OS (all p < 0.005), the association was not significant for PSA30 or PSA50 response. CTC and PSA response were discordant in over 50% of cases, with outcome driven by CTC response in these patients. The c-index values for OS were superior for early CTC changes compared to PSA response endpoints, and similar to 6-month rPFS. Early CTC declines were good predictors of improved outcomes in mCRPC patients treated with docetaxel in this small study, offering a superior and/or earlier estimation of docetaxel benefit in comparison to PSA or rPFS that merits further confirmation in larger studies.
Filiaciones:
Lozano R:
Inst Biomed Res Malaga IBIMA, Genitourinary Canc Traslat Res Grp, Malaga 29010, Spain
Spanish Natl Canc Res Ctr CNIO, Prostate Canc Clin Res Unit, Madrid 28029, Spain
Lorente D:
Spanish Natl Canc Res Ctr CNIO, Prostate Canc Clin Res Unit, Madrid 28029, Spain
Hosp Prov Castellon, Serv Oncol Med, Castellon De La Plana 12004, Spain
Aragon I:
Inst Biomed Res Malaga IBIMA, Genitourinary Canc Traslat Res Grp, Malaga 29010, Spain
Spanish Natl Canc Res Ctr CNIO, Prostate Canc Clin Res Unit, Madrid 28029, Spain
Romero-Laorden N:
Spanish Natl Canc Res Ctr CNIO, Prostate Canc Clin Res Unit, Madrid 28029, Spain
Hosp Univ La Princesa, Madrid 28006, Spain
Nombela P:
Spanish Natl Canc Res Ctr CNIO, Prostate Canc Clin Res Unit, Madrid 28029, Spain
Mateo J:
Inst Canc Res, London SW7 3RP, England
Royal Marsden NHS Fdn Trust, London, England
Vall dHebron Inst Oncol VHIO, Barcelona 08035, Spain
Reid A:
Inst Canc Res, London SW7 3RP, England
Royal Marsden NHS Fdn Trust, London, England
Cendon Y:
Spanish Natl Canc Res Ctr CNIO, Prostate Canc Clin Res Unit, Madrid 28029, Spain
Bianchini D:
Inst Canc Res, London SW7 3RP, England
Royal Marsden NHS Fdn Trust, London, England
Llacer C:
Inst Biomed Res Malaga IBIMA, Genitourinary Canc Traslat Res Grp, Malaga 29010, Spain
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic 3000, Australia
Sandhu S:
Inst Canc Res, London SW7 3RP, England
Royal Marsden NHS Fdn Trust, London, England
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic 3000, Australia
Sharp A:
Inst Canc Res, London SW7 3RP, England
Royal Marsden NHS Fdn Trust, London, England
Rescigno P:
Inst Canc Res, London SW7 3RP, England
Royal Marsden NHS Fdn Trust, London, England
FPO IRCCS, Candiolo Canc Inst, I-10060 Turin, Italy
Garces T:
Inst Biomed Res Malaga IBIMA, Genitourinary Canc Traslat Res Grp, Malaga 29010, Spain
Spanish Natl Canc Res Ctr CNIO, Prostate Canc Clin Res Unit, Madrid 28029, Spain
Pacheco M:
Inst Biomed Res Malaga IBIMA, Genitourinary Canc Traslat Res Grp, Malaga 29010, Spain
Spanish Natl Canc Res Ctr CNIO, Prostate Canc Clin Res Unit, Madrid 28029, Spain
Flohr P:
Inst Canc Res, London SW7 3RP, England
Massard C:
Inst Canc Res, London SW7 3RP, England
Fac Med Paris Sud XI, Inst Gustave Roussy, Dept Med Oncol, F-94805 Villejuif, France
Lopez-Casas P:
Spanish Natl Canc Res Ctr CNIO, Prostate Canc Clin Res Unit, Madrid 28029, Spain
Castro E:
Inst Biomed Res Malaga IBIMA, Genitourinary Canc Traslat Res Grp, Malaga 29010, Spain
Spanish Natl Canc Res Ctr CNIO, Prostate Canc Clin Res Unit, Madrid 28029, Spain
de Bono J:
Inst Canc Res, London SW7 3RP, England
Royal Marsden NHS Fdn Trust, London, England
Olmos D:
Inst Biomed Res Malaga IBIMA, Genitourinary Canc Traslat Res Grp, Malaga 29010, Spain
Spanish Natl Canc Res Ctr CNIO, Prostate Canc Clin Res Unit, Madrid 28029, Spain
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