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Journal of Cancer Research and Clinical Oncology

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01.08.2015 | Original Article – Clinical Oncology

Circulating tumor cells versus objective response assessment predicting survival in metastatic castration-resistant prostate cancer patients treated with docetaxel chemotherapy

verfasst von: M. Thalgott, M. M. Heck, M. Eiber, M. Souvatzoglou, G. Hatzichristodoulou, V. Kehl, B. J. Krause, B. Rack, M. Retz, J. E. Gschwend, U. Andergassen, R. Nawroth

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 8/2015

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Abstract

Purpose

Circulating tumor cell (CTC) counts might display a superior prognostic value for overall survival (OS) compared to objective response criteria (OR) in metastatic castration-resistant prostate cancer (mCRPC) patients.

Methods

CTCs were detected using the CellSearch™ System out of 122 samples during docetaxel chemotherapy (75 mg/m²) at baseline (q0) and after 1 (q1), 4 (q4) and 10 (q10) cycles, in mCRPC patients (n = 33). OR was evaluated by morphologic RECIST and clinical criteria after 4 (q4) and 10 (q10) cycles.

Results

For OS, analyses revealed a significant prognostic value for categorical (<5 vs. ≥5) CTC counts (q0, p = 0.005; q1, p = 0.001; q4, p < 0.001; q10, p = 0.002), RECIST (q4, p < 0.001; q10, p = 0.02) and clinical criteria (q4, p < 0.001; q10, p = 0.02). Concordance of CTC counts with OR revealed a sensitivity of 83.3–87.5 % and a specificity of 68.0–76.5 % with complementary discriminatory power for OS. Comparing CTC counts with concomitant OR at q4 in multivariate analyses, an independent prognostic value for OS was found for CTC counts (HR 3.3; p = 0.02) similar to clinical (HR 4.9; p = 0.02) and radiologic response (HR 3.4; p = 0.051). Comparing the predictive value for death, early post-treatment CTC counts at q1 demonstrated significant accuracy with an area under the curve of 79.5 % (p = 0.004) similar to CTC counts at q4 (76.7 %; p = 0.009). Radiologic and clinical response at q4 displayed accuracy similar to early CTC counts at q1 (72.2 %; p = 0.03 and 75.0 %; p = 0.02) despite low sensitivities.

Conclusions

CTC counts appear to be an earlier and more sensitive predictor for survival and treatment response than current OR approaches and may provide complementary information toward individualized treatment strategies.

Becker TM, Caixeiro NJ, Lim SH, Tognela A, Kienzle N, Scott KF, Spring KJ, de Souza P (2014) New frontiers in circulating tumor cell analysis: a reference guide for biomolecular profiling toward translational clinical use. Int J Cancer 134(11):2523–2533PubMedCrossRef

Berthold DR, Pond GR, Roessner M, de Wit R, Eisenberger M, Tannock AI, TAX-327 investigators (2008) Treatment of hormone-refractory prostate cancer with docetaxel or mitoxantrone: relationships between prostate-specific antigen, pain, and quality of life response and survival in the TAX-327 study. Clin Cancer Res 14(9):2763–2767PubMedCrossRef

Budd GT, Cristofanilli M, Ellis MJ, Stopeck A, Borden E, Miller MC, Matera J, Repollet M, Doyle GV, Terstappen LW, Hayes DF (2006) Circulating tumor cells versus imaging–predicting overall survival in metastatic breast cancer. Clin Cancer Res 12(21):6403–6409PubMedCrossRef

Caixeiro NJ, Kienzle N, Lim SH, Spring KJ, Tognela A, Scott KF, de Souza P, Becker TM (2014) Circulating tumour cells—a bona fide cause of metastatic cancer. Cancer Metastasis Rev 33(2–3):747–756PubMedCrossRef

Coumans FA, Ligthart ST, Terstappen LW (2012) Interpretation of changes in circulating tumor cell counts. Transl Oncol 5(6):486–491PubMedPubMedCentralCrossRef

De Bono JS, Scher HI, Montgomery RB, Parker C, Miller MC, Tissing H, Doyle GV, Terstappen LW, Pienta KJ, Raghavan D (2008) Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res 14(19):6302–6309PubMedCrossRef

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247PubMedCrossRef

Fleming MT, Morris MJ, Heller G, Scher HI (2006) Post-therapy changes in PSA as an outcome measure in prostate cancer clinical trials. Nat Clin Pract Oncol 3(12):658–667PubMedCrossRef

Goldkorn A, Ely B, Quinn DI, Tangen CM, Fink LM, Xu T, Twardowski P, Van Veldhuizen PJ, Agarwal N, Carducci MA, Monk JP 3rd, Datar RH, Garzotto M, Mack PC, Lara P Jr, Higano CS, Hussain M, Thompson IM Jr, Cote RJ, Vogelzang NJ (2014) Circulating tumor cell counts are prognostic of overall survival in SWOG S0421: a phase III trial of docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer. J Clin Oncol 32(11):1136–1142PubMedPubMedCentralCrossRef

Gomella LG, Sartor AO (2014) The current role and limitations of surrogate endpoints in advanced prostate cancer. Urol Oncol 32(1):28.e1–28.e9CrossRef

Gonzales JC, Fink LM, Goodman OB Jr, Symanowski JT, Vogelzang NJ, Ward DC (2011) Comparison of circulating MicroRNA 141 to circulating tumor cells, lactate dehydrogenase, and prostate-specific antigen for determining treatment response in patients with metastatic prostate cancer. Clin Genitourin Cancer 9(1):39–45PubMedCrossRef

Heidenreich A, Albers P, Classen J, Graefen M, Gschwend J, Kotzerke J, Krege S, Lehmann J, Rohde D, Schmidberger H, Uder M, Zeeb H (2010) Imaging studies in metastatic urogenital cancer patients undergoing systemic therapy: recommendations of a multidisciplinary consensus meeting of the Association of Urological Oncology of the German Cancer Society. Urol Int 85(1):1–10PubMedCrossRef

Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, Mason M, Matveev V, Wiegel T, Zattoni F, Mottet N (2014) EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol 65(2):467–479PubMedCrossRef

Huang X, Chau CH, Figg WD (2012) Challenges to improved therapeutics for metastatic castrate resistant prostate cancer: from recent successes and failures. J Hematol Oncol 5:35PubMedPubMedCentralCrossRef

Khoury JD, Adcock DM, Chan F, Symanowski JT, Tiefenbacher S, Goodman O, Paz L, Ma Y, Ward DC, Vogelzang NJ, Fink LM (2010) Increases in quantitative D-dimer levels correlate with progressive disease better than circulating tumor cell counts in patients with refractory prostate cancer. Am J Clin Pathol 134(6):964–969PubMedCrossRef

Liu H, Zhang X, Li J, Sun B, Qian H, Yin Z (2015) The biological and clinical importance of epithelial-mesenchymal transition in circulating tumor cells. J Cancer Res Clin Oncol 141(2):189–201PubMedCrossRef

Loh J, Jovanovic L, Lehman M, Capp A, Pryor D, Harris M, Nelson C, Martin J (2014) Circulating tumor cell detection in high-risk non-metastatic prostate cancer. J Cancer Res Clin Oncol 140(12):2157–2162PubMedCrossRef

Okegawa T, Nutahara K, Higashihara E (2008) Immunomagnetic quantification of circulating tumor cells as a prognostic factor of androgen deprivation responsiveness in patients with hormone naive metastatic prostate cancer. J Urol 180(4):1342–1347PubMedCrossRef

Okegawa T, Nutahara K, Higashihara E (2009) Prognostic significance of circulating tumor cells in patients with hormone refractory prostate cancer. J Urol 181(3):1091–1097PubMedCrossRef

Olmos D, Arkenau HT, Ang JE, Ledaki I, Attard G, Carden CP, Reid AH, A’Hern R, Fong PC, Oomen NB, Molife R, Dearnaley D, Parker C, Terstappen LW, de Bono JS (2009) Circulating tumour cell (CTC) counts as intermediate end points in castration resistant prostate cancer (CRPC): a single-centre experience. Ann Oncol 20(1):27–33PubMedCrossRef

Pantel K, Alix-Panabières C (2012) The potential of circulating tumor cells as a liquid biopsy to guide therapy in prostate cancer. Cancer Discov 2(11):974–975PubMedCrossRef

Petrylak DP, Tangen CM, Hussain MH, Lara PN Jr, Jones JA, Taplin ME, Burch PA, Berry D, Moinpour C, Kohli M, Benson MC, Small EJ, Raghavan D, Crawford ED (2004) Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 351:1513–1520PubMedCrossRef

Rink M, Chun FK, Minner S, Friedrich M, Mauermann O, Heinzer H, Huland H, Fisch M, Pantel K, Riethdorf S (2011) Detection of circulating tumour cells in peripheral blood of patients with advanced non-metastatic bladder cancer. BJU Int 107(10):1668–1675PubMedCrossRef

Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, Eisenberger MA, Higano C, Bubley GJ, Dreicer R, Petrylak D, Kantoff P, Basch E, Kelly WK, Figg WD, Small EJ, Beer TM, Wilding G, Martin A, Hussain M, Prostate Cancer Clinical Trials Working Group (2008) Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol 26(7):1148–1159PubMedPubMedCentralCrossRef

Scher HI, Jia X, de Bono JS, Fleisher M, Pienta KJ, Raghavan D, Heller G (2009) Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer: a reanalysis of IMMC38 trial data. Lancet Oncol 10(3):233–239PubMedPubMedCentralCrossRef

Schindlbeck C, Andergassen U, Hofmann S, Jückstock J, Jeschke U, Sommer H, Friese K, Janni W, Rack B (2013) Comparison of circulating tumor cells (CTC) in peripheral blood and disseminated tumor cells in the bone marrow (DTC-BM) of breast cancer patients. J Cancer Res Clin Oncol 139(6):1055–1062PubMedCrossRef

Strijbos MH, Gratama JW, Schmitz PI, Rao C, Onstenk W, Doyle GV, Miller MC, de Wit R, Terstappen LW, Sleijfer S (2010) Circulating endothelial cells, circulating tumour cells, tissue factor, endothelin-1 and overall survival in prostate cancer patients treated with docetaxel. Eur J Cancer 46(11):2027–2035PubMedCrossRef

Sun YF, Yang XR, Zhou J, Qiu SJ, Fan J, Xu Y (2011) Circulating tumor cells: advances in detection methods, biological issues, and clinical relevance. J Cancer Res Clin Oncol 137(8):1151–1173PubMedCrossRef

Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Théodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA, TAX 327 Investigators (2004) Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351:1502–1512PubMedCrossRef

Thalgott M, Rack B, Maurer T, Souvatzoglou M, Eiber M, Kreß V, Heck MM, Andergassen U, Nawroth R, Gschwend JE, Retz M (2013) Detection of circulating tumor cells in different stages of prostate cancer. J Cancer Res Clin Oncol 139(5):755–763PubMedCrossRef

Titel: Circulating tumor cells versus objective response assessment predicting survival in metastatic castration-resistant prostate cancer patients treated with docetaxel chemotherapy
verfasst von: M. Thalgott
M. M. Heck
M. Eiber
M. Souvatzoglou
G. Hatzichristodoulou
V. Kehl
B. J. Krause
B. Rack
M. Retz
J. E. Gschwend
U. Andergassen
R. Nawroth
Publikationsdatum: 01.08.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 8/2015
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-015-1936-z

Springer Medizin

Circulating tumor cells versus objective response assessment predicting survival in metastatic castration-resistant prostate cancer patients treated with docetaxel chemotherapy