A Refinement of Clinical Tumor Marker Monitoring: Why Not Use an Inverse Value of Doubling Time?

Abstract

Objectives: The aim of this study was to compare prostate-specific antigen (PSA) kinetics - half-life time (HT), doubling time (DT), and elimination rate PSA (ePSA) in prostate cancer (PCa) monitoring. Implementation of ePSA in clinical practice could help simplify patient monitoring in the remission phase.

Materials and methods: A total of 49 PCa patients were examined by their PSA tests before prostatectomy and after 30 days, 91 days, and 24 months. Conventional PSA rate of change parameters (HT and DT) were compared to a new clinically understandable ePSA parameter.

Results: We observed that implementation of inverse value (ePSA) rather than HT or DT has distinct advantages: (1) values are valid when PSA is unchanged (ePSA equals zero), (2) the concept of ePSA can be easily understood, as it is a growth fraction, (3) ePSA fluctuates within a narrow range and is thus easy to interpret, and (4) there are no mathematical flaws (no positive skewing).

Conclusion: Exploring ePSA norm as ≤0% could help spot biochemical recurrence in a timely manner. Primary health care providers tend to use an irrelevant PSA threshold, that is, 4.0 ng/mL, in postoperative follow-up. The delayed referrals of patients in remission might be reduced if ePSA testing is adopted.

Keywords: Cancer relapse; Prostate cancer; Prostate-specific antigen; Tumor markers.

Fig. 1

The value of logarithm in evaluating TM development. The PSA data (preoperative, day 30 and day 91) of the same cohort are shown using a linear scale (a) and log scale (b). Any claim in colloquial clinical language saying TM “percent increase” (decrease) does not reflect the evolution of TM within a given time interval. Importantly, these claims rarely indicate a precise time interval between two separate TMs. An exact time interval and log TM ratio are two basic components which can describe the “speed” of progress or decay of TM. Trying to squeeze a TM ratio into linear concept of increase [11] results in a discussion on which of the 7 patterns is the most informative. Any new confirmative TM test should be evaluated if it fits into the pattern of the previous two, in a log TM scale only (c). The exact timing of planned A3 point determination is not that important, provided the TM is tested with the same instrument. The availability of multiple TM points is advantageous (c). Calculation of an eTM with multiple points for each patient is available using nomograms with minimal conversion of DT into eTM [8]. A hospital lab can produce automatic reports for eTM if previous data for the same patient are available. A clinician can easily adopt the simplicity of growth fraction concept and can assume that a ∼1% daily increase in TM will result in a roughly 30% increase of TM value within a month (1% per day results roughly in 30% per month) (d). TM, tumor marker; PSA, prostate-specific antigen; eTM, elimination rate TM; DT, doubling time; RP, radical prostatectomy; ePSA, elimination rate PSA.