Recomendaciones para la optimización del uso de marcadores tumorales de utilización frecuente. Recomendación (2018)

Consensus of the Spanish society of laboratory medicine and the Spanish society of medical oncology on the methodology and criteria for evaluation of circulating tumour markers in breast cancer

“…It is therefore necessary to correctly interpret any increase in a TM. In case there is a discrepancy between the clinical and analytical results, the following steps are recommended [7][8][9]: (i) ruling out a benign pathology (see below); (ii) investigating any methodological issues as mentioned above; and (iii) performing a second measurement 3-4 weeks later (or at least a period longer than the TM's plasma half-life, which is 15-20 days for most); then evaluating the increase: (i) if the increase in concentration is < 15%, or if there is a decrease, then the change is not related to the evolution of the neoplasia and may be due to other reasons such as the analytical method or fluctuations in the TM itself; (ii) if the increase is 15-25%, then it is advisable to perform a second measurement 3-4 weeks (or as described above) later; (iii) if there are thus two separate increases > 25% or a single-period increase > 50%, then disease progression must be suspected. Therefore, the definition of a clinically significant change that marks the progression of neoplasia can be generally established as two separate increases of > 25% or a single-period increase > 50%, in the absence of benign pathology or methodological issues to explain it.…”

“…The correct interpretation of a TM is essential to avoid false positives and false negatives. Errors can occur in the different phases of the laboratory process (preanalytical, analytical, and postanalytical), which need to be identified to correctly interpret the results and assess their clinical impact [ 8 ].…”

“…The theoretical basis of the RCV in relation to TMs is presented in a recent guideline from the SEQC ML [ 8 ]. The TMs most used in breast cancer are carbohydrate 15.3 (CA15.3) and carcinoembryonic antigen (CEA).…”

“…The TMs most used in breast cancer are carbohydrate 15.3 (CA15.3) and carcinoembryonic antigen (CEA). For CA15.3 and CEA, the CV i is known (6.3–11.2% for CA15.3 and 9.9–12.9% for CEA), and the RCV can be calculated: 19–34% for CA15.3 and 30–40% for CEA [ 8 ]. Therefore, as a definition of significant analytical change, an increase > 25%, or more conservatively > 50%, over the previous concentration can be generally established.…”

“…Therefore, as explained in Sect. 2.1 , whenever there is a significant change in the level of a TM in patient follow-up, other conditions should be excluded, especially changes in liver and kidney function, that may explain its elevation (Table 1 ) [ 8 , 23 , 24 ]. When biochemical progression has been demonstrated with serial determinations of a TM, imaging techniques should be performed to confirm relapse.…”