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
ISSN: 20726694





Cancers
Editorial
Multidisciplinary Digital Publishing Institute (MDPI), ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND, Suiza
Tipo de documento: Article
Volumen: 13 Número: 10
Páginas:
WOS Id: 000654676100001
ID de PubMed: 34066080
imagen Green Published, gold

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