Abstract
Simple SummaryThe 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.
Highlights
The treatment landscape for metastatic castration-resistant prostate cancerhas rapidly evolved in recent years
In order to enrich for patients with Circulating tumor cell (CTC) counts >5/7.5 mL, patients in both studies were required to meet at least two of the following criteria associated with high CTC counts (≥5 CTCs) [11]: bone metastases, elevated alkaline phosphatase (ALP > upper limit of normal (ULN)), hemoglobin (Hb) < 10 g/dL, baseline prostate-specific antigen (PSA) > 150 ng/mL and/or ≥2 prior lines of hormonal therapies
A total of 80 (91.9%) metastatic castration-resistant prostate cancer (mCRPC) patients out of 87 patients screened between both studies (RMH and PROSTAC-CTC) met the eligibility criteria and were included in this analysis (Figure S1)
Summary
The treatment landscape for metastatic castration-resistant prostate cancer (mCRPC)has rapidly evolved in recent years. Several drugs have demonstrated an improvement in overall survival (OS) in this setting [1], the optimal treatment sequence has not been established. The development of early treatment response biomarkers is urgently needed to avoid unnecessary exposure to ineffective therapy with undesirable toxicities and to accelerate the process of drug development. Recommendations for the assessment of treatment response have been developed by the Prostate Cancer Working Group (PCWG) [2]. These are mainly based on computer tomography (CT) or bone scans, prostate-specific antigen (PSA) and clinical deterioration. The evaluation of radiographic response to treatment in advanced prostate cancer is significantly hampered by the fact that over 50% of patients present with bone-only disease, which is non-evaluable by RECIST criteria. On the other hand, do not usually change in the setting of a response and can only define progression after at least 14 weeks have elapsed, due to the potential for spurious flare reactions
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