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Circulating Tumor Cells Predict Survival Benefit from Treatment in Metastatic Castration-Resistant Prostate Cancer

Authors' Affiliations: ¹ Royal Marsden Hospital, London, United Kingdom; ² Genitourinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York; ³ University of Washington, Seattle, Washington; ⁴ Immunicon Corporation, Huntingdon Valley, Pennsylvania; ⁵ University of Michigan, Ann Arbor, Michigan; and ⁶ Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio

Requests for reprints: Johann S. de Bono, Section of Medicine, Institute of Cancer Research, Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, United Kingdom. Phone: 44-20-8722; Fax: 44-20-8642-7979; E-mail: jdebono{at}icr.ac.uk.

Purpose: A method for enumerating circulating tumor cells (CTC) has received regulatory clearance. The primary objective of this prospective study was to establish the relationship between posttreatment CTC count and overall survival (OS) in castration-resistant prostate cancer (CRPC). Secondary objectives included determining the prognostic utility of CTC measurement before initiating therapy, and the relationship of CTC to prostate-specific antigen (PSA) changes and OS at these and other time points.

Experimental Design: Blood was drawn from CRPC patients with progressive disease starting a new line of chemotherapy before treatment and monthly thereafter. Patients were stratified into predetermined Favorable or Unfavorable groups (<5 and 5 CTC/7.5mL).

Results: Two hundred thirty-one of 276 enrolled patients (84%) were evaluable. Patients with Unfavorable pretreatment CTC (57%) had shorter OS (median OS, 11.5 versus 21.7 months; Cox hazard ratio, 3.3; P < 0.0001). Unfavorable posttreatment CTC counts also predicted shorter OS at 2 to 5, 6 to 8, 9 to 12, and 13 to 20 weeks (median OS, 6.7-9.5 versus 19.6-20.7 months; Cox hazard ratio, 3.6-6.5; P < 0.0001). CTC counts predicted OS better than PSA decrement algorithms at all time points; area under the receiver operator curve for CTC was 81% to 87% and 58% to 68% for 30% PSA reduction (P = 0.0218). Prognosis for patients with (a) Unfavorable baseline CTC who converted to Favorable CTC improved (6.8 to 21.3 months); (b) Favorable baseline CTC who converted to Unfavorable worsened (>26 to 9.3 months).

Conclusions: CTC are the most accurate and independent predictor of OS in CRPC. These data led to Food and Drug Administration clearance of this assay for the evaluation of CRPC.

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