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

  • Original Article – Clinical Oncology
  • Published:
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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.

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Acknowledgments

We thank Janet Mindes, PhD, NYC, USA, for her editing assistance and Carolin Kronester, earning her doctorate on this work. The study was supported by Sanofi-Aventis, Frankfurt, Germany, and the Siegfried Gruber-Foundation, Munich, Germany.

Conflict of interest

We declare that we have no conflict of interest.

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Author notes

    Authors and Affiliations

    1. Department of Urology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675, Munich, Germany

      M. Thalgott, M. M. Heck, G. Hatzichristodoulou, M. Retz, J. E. Gschwend & R. Nawroth

    2. Department of Gynecology and Obstetrics, Klinikum Innenstadt, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany

      B. Rack & U. Andergassen

    3. Department of Radiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

      M. Eiber

    4. Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

      M. Souvatzoglou

    5. Institute of Medical Statistics and Epidemiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

      V. Kehl

    6. Department of Nuclear Medicine, Universitätsklinikum Rostock, Rostock, Germany

      B. J. Krause

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    Correspondence to M. Thalgott.

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    U. Andergassen and R. Nawroth have contributed equally to this work.

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    Thalgott, M., Heck, M.M., Eiber, M. et al. Circulating tumor cells versus objective response assessment predicting survival in metastatic castration-resistant prostate cancer patients treated with docetaxel chemotherapy. J Cancer Res Clin Oncol 141, 1457–1464 (2015). https://doi.org/10.1007/s00432-015-1936-z

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    • DOI: https://doi.org/10.1007/s00432-015-1936-z

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