Carcinoembryonic Antigen, Arginine Vasopressin and Calcitonin as Markers of Early Small-Cell Lung Cancer Relapse

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Abstract
Patients with small-cell lung cancer (SCLC) underwent serial blood monitoring during remission: 66 were tested for carcinoembryonic antigen (CEA) and calcitonin (CTN), including 40 who were concomitantly tested for arginine vasopression (AVP) as well. 83% of the patients had at least one assay elevated prior to induction therapy. By serial monitoring, blood concentrations reflected disease course and reached lowest levels at remission. CEA, AVP and CTN shifted along the course of disease independently of each other; a normal pretreatment titer did not preclude its rise at a later phase, while an initially elevated assay could normalize at remission and stay normal thereafter. The median lead time (LT) to clinically diagnosed relapse, for limited-disease patients, was 229 days for complete and 90 days for partial remitters. Patients with extensive disease had similar LT values. LT to local recurrence was shorter than to distant relapse. Remission AVP titers of up to 6 ng/ml conferred disease-free survival (DFS) longer than that associated with higher titers (median DFS 518 vs. 211 days, respectively; p = 0.045 for curve differences). The relative risk (RR) of relapse associated with pretreatment patient characteristics and with absence or presence of tumor marker normalization at remission was estimated by the Cox proportional hazards model. This analysis revealed that the RR of relapse conferred by pretreatment attributes, e.g. disease extent, was considerably modified by biochemical co-variates at remission, e.g. serum CEA level relative to a 3 ng/ml cutoff point.