Transient therapy-related surge in serum tumor biomarkers: Characterizing behavior and postulating its biologic role

A phenomenon of serum tumor biomarker surge or flare that ensues shortly after initiating cancer therapy and that may precede the actual therapeutic response-related decline is poorly understood and remains under-appreciated. However, it may have a significant clinical implication as it could be misinterpreted in clinical practice as therapeutic failure and lead to a premature discontinuation of potentially effective therapy. Therefore, in the present study, attempts have been made to understand the behavior of this phenomenon with respect to a reported median incidence, duration, and its relationship to clinical response. The results of these analyses suggest a significantly lower incidence of this phenomenon with carcinoembryonic antigen (CEA) as determined in colorectal cancer and prostate specific antigen (PSA) in prostate cancer as compared to the other biomarkers studied (p = 0.006). Furthermore, regardless of the type of biomarker or the extent of its incidence, a therapy-related initial surge appears to correlate with eventual response to therapy. Although, the biologic significance of this phenomenon is currently elusive, two distinct hypothesis-generating cases with CEA and alpha-fetoprotein (AFP) are presented that, if supported by further research, would provide insights into the role of a biomarker surge in overall tumor growth control by cancer therapy.