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Purpose: To investigate the relationships between circulating tumor cells (CTCs), free circulating DNA(fcDNA) and biochemical response in prostate cancer patients treated primarily versus salvage radiotherapy(RT).Methods and Materials: Blood was collected prospectively from patients, enrolled in two institutionalPhase II trials for primary and salvage RT. Three blood samples were collected at: (i) prior to treatment [RTor androgen deprivation therapy (ADT)], (ii) last week of RT, and (iii) three months post-RT. CTCs werequantified in 31 samples from 12 primary patients and 30 samples from 12 salvage patients; fcDNA wereanalyzed in 11 primary (28 samples) and 5 (9 samples) salvage patients. CTCs were visualized byimmunofluorescence after microfilter capture and fcDNA was quantified using real-time Polymerase chainreaction (PCR). CTCs and fcDNA were correlated with early biochemical response by subdividing patientsinto early favorable and unfavorable response at 3 months after RT.Results: For those treated primarily, there was a direct correlation with CTC counts and prostate specificantigen (PSA) pre-RT that changed to a reciprocal relationship 3 months post-RT. CTCs increasedsignificantly (p=0.03) at 3 months after primary RT in the biochemical favorable patients, while nosignificant association was observed for fcDNA. Correspondingly, post-RT fcDNA levels were inverselyrelated to CTC counts. In salvage patients, the number of CTCs was related to pre-RT PSA, but it was notcorrelated to RT response. In post-RT series, a significant direct correlation was observed between CTCsand PSA.Conclusion: Our preliminary studies suggest that RT affects CTC counts, which are thus associated withprostate cancer biochemical response. A larger cohort with longer follow-up will be needed to establish theassociation with more recognized treatment endpoints.

Contrasting Circulating Tumor Cells and Free Circulating DNA Responses in Men Treated for Prostate Cancer after Primary Versus Salvage Radiotherapy