Variability among prostate specific antigen (PSA) assays may increase the risk of misdiagnosing biochemical failure in prostate cancer patients, Indian researchers concluded in a study published in Clinical Biochemistry.

“Although PSA is an integral part of prostate cancer management, PSA measurement is subject to variability owing to the presence of several types of PSA assays in different formats,” the article stated. There are chemiluminescence-based systems, which are used for automated assays (a-PSA), and ELISA-based systems or manual measurement assays (m-PSA). A-PSA systems are commonly used by the best-equipped centers, yet the ELISA assay is still popular among many labs and hospitals. Developing countries in particular tend to favor the latter for economic reasons.

Inter-assay variability issues remain, however, despite efforts to improve characterization of antibodies, and the World Health Organization’s attempt to standardize PSA methods. “With variability in assay formats, analytical sensitivity, capture-detection antibodies and calibrator preparations the results reported by clinical laboratories are variables causing discordance in PSA concentration measurements for clinical purpose,” the authors noted.

This issue could impact clinical decisions involving the management of prostate cancer. “If different assays yield different PSA concentrations for the same serum sample, a proportion of patients might have management-altering consequences,” the researchers cautioned.

The authors conducted a prospective, cross-sectional, observational study to compare differences among a-PSA and m-PSA assays. They used sera from 495 patients (425 with prostate cancer and 70 with Benign Prostatic Hyperplasia or BPH) and measured the samples with three a-PSA and three m-PSA assays.

The investigators also wanted to assess how variability among assays impacted clinical objectives such as risk stratification, detection of biochemical failure post-radiotherapy, variability with rising, and variability in cancer versus BPH.

PSA monitoring is especially crucial in assessing biochemical failure and in administering timely interventions in radiotherapy patients. However, in analyzing inter-assay agreement that defines biochemical failure in these patients, the researchers reported “poor agreement among all the assays” with a remarkable 50% chance of under- or over-diagnosing biochemical failure. This could result in either treatment delays or a “false alarm” effect, the researchers indicated.

Overall, the study found poor agreement and high variability among all of the assays, although discordance was especially high among the m-PSA assays. Compared with the a-PSA assays, whose kappa results ranged from 86% to 90%, “there was poor agreement among the ELISA-based assays, with kappa ranging from 52% to 75%,” according to the results.

For this reason, clinicians should exercise caution when analyzing a variety of PSA values from a large patient population, and hold off on making any clinical management decisions until they compare results from the two types of assays.

The researchers also suggested that “the assay method used and the brand name of the assay used must be given in every laboratory report to alert the physician to any change in the assay method.”