Better prognostication of clinically localized prostate cancer (PCA) is urgently needed. Former studies using different study end-points provided controversial results regarding the prognostic value of serum chromogranin A (CGA) in clinically localized PCA. However, serum CGA was not tested for correlation with the most significant study end-point of long-term disease-specific survival (DSS). CGA and matrix metalloproteinase-7 (MMP7) levels were measured by the BRAHMS KRYPTOR in two independent patient groups with 127 serum and 110 plasma samples. CGA and MMP7 concentrations were correlated with clinicopathological and survival data. In addition, we tested the combinations of CGA with PSA and with a currently identified prognostic factor, MMP7, for their prognostic value. CGA concentrations were significantly elevated in advanced compared to clinically localized cases both in serum and plasma samples (45 vs. 23 ng/ml, p < 0.001 and; 41 vs. 22 ng/ml; p = 0.002 respectively). In accordance, high CGA levels were correlated with poor DSS. In clinically localized cases, CGA levels alone were not prognostic, but its dichotomized combinations with PSA or MMP7 were independently associated with DSS (HR: 4.88, 95% CI: 1.35-17.71, p = 0.016, HR: 7.46, 1.65-33.63, p = 0.009, respectively). Elevated serum CGA levels in progressed PCA and its prognostic value suggest a potential for CGA in disease monitoring. Our results revealed no independent prognostic value for CGA as a single serum marker in clinically localized cases. However, when combining with PSA or MMP7, CGA may improve both marker's performance in distinguishing between clinically significant and indolent PCAs.
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