Lower limits of detection, biological detection limits, functional sensitivity, or residual cancer detection limit? Sensitivity reports on prostate-specific antigen assays mislead clinicians.

It is increasingly important for clinicians to know whether prostate-specific antigen (PSA) is detectable or undetectable in serum of a patient being treated for prostate cancer.' The lower the PSA falls after treatment, the more sensitive the cancer is to that therapy and the longer the patient is likely to live. However, clinicians are faced with a bewildering series of reports from different reference laboratories, often laboratories using the same assay. To take only one example, the " sensitivity " (lower limit of detection?) of the Hybritech Tandem#{174}-Rassay (San Diego, CA) is variously reported as <0.05 .egfL, <0.1 i.tg/L, <0.2 jLgfL, and 0.3-0.5 1tig/L. Some of this confusion is caused by the terminology used by laboratorians, which is then misinterpreted by the clinicians. We should all remember GB. Shaw's famous comment that the biggest single problem with communication is the illusion that it has been accomplished. A good example is the laboratorian's use of the term " lower limit of detection " (LLD). Clinicians who see this term rightly believe that any serum PSA value above this number indicates a " positive " result; i.e., there is detectable PSA in the serum of the patient. Unfortunately, commercialism has led assay manufacturers to tout their differences in LLD among assays to the point where laboratorians believe that the LLD has clinical significance and subsequently relay these values to clini-cians on the laboratory report. Traditionally, the LLD is determined by running the zero calibrator of the assay many times in the same assay run (intraassay variation) to determine the imprecision of the zero calibrator determination [1, 2]. Many assays for PSA utilize bovine serum albumin (BSA) as their matrix, although other animal sera are also used. However, BSA is a highly purified simple protein that bears no resemblance to the complexities of human serum. Intraassay variation with such simple proteins might be elegantly low, but this would be misleading for the clinician and potentially harmful to the patient. Determination of the LLD for thyrotropin assays in the diagnosis of euthyroid-ism is quite similar to the problem with PSA assays. As Spencer et al. note, the " American Thyroid Association now considers such intraassay determinations of detection limit to be clinically irrelevant and to give an overly optimistic estimate of assay performance " [1]. Clinicians responsible for management of patients with prostate cancer need to know what value of PSA in male serum …