Serum levels of CA 125 and markers reputed as specific for cancers in relevant locations (squamous cell carcinoma, SCC, carcinoembryonic antigen, CEA, CA 19.9, α-fetoprotein, AFP) were determined in 107 patients with gastrointestinal (GI) carcinomas. The aim of this study was to assess their individual and combined sensitivities, and the power of CA 125 in excluding primary ovarian epithelial cancer from GI primary. Serum CA 125 levels (in U/ml) ranged from nondetectable to 400 in patients with esophageal, to 570 in those with gastric, and to 300 in patients with colorectal carcinoma. The levels for liver secondaries, pancreatic, and hepatocellular carcinoma were 480, 2,720 and 1,100 U/ml, respectively. Serum SCC antigen was elevated in all patients with esophageal cancer, CEA or CA 19.9 in 52% of patients with gastric cancer and in 63% with liver secondaries, and CEA in 95% of patients with colorectal cancer; whereas serum CA 125 above 65 U/ml was found in 25% of this subgroup, but only in those with already an elevated concentration of specific marker(s). Serum CEA or CA 19.9 was elevated in 71%, CA 125 in 59% of patients with pancreatic cancer; the latter mostly in those with already elevated CEA or CA 19.9. Serum AFP was elevated in 84% and CA 125 in 40% of patients with hepatoma; the latter mostly in those with already an elevated AFP. CA 125 values exceeding 1,000 U/ml were found in 1 patient with pancreatic cancer (2,720 U/ml) and in 2 with hepatoma (1,050 and 1 100 U/ml). These findings illustrate the nonspecificity of the CA 125 antigen, its small if any advantage compared to the specific markers, and they diminish its role as a marker for primary ovarian cancer from GI primary unless it exceeds 2,800 U/ml.
Serum concentrations were determined serially in two groups of patients with colorectal carcinoma: in 123 after curative resection and in 34 with residual cancer. Of the first group, in 98 serum CEA fluctuated within the normal range or with a 2-fold larger amplitude evidencing effective surgery because only 9 had recurrence; in 25 serum CEA rose persistently from a postoperative nadir indicating relapse, mostly liver metastases. Of the 34 patients with relapse, 3 had clinically and 7 CEA-directed second-look laparotomy; although 7 had operation with curative intent, only 3 remained disease-free. In the second group, there were 26 patients after palliative surgery and 8 during nonsurgical treatment. Serum CEA fluctuated within the normal range in 2 patients in remission and in 3 with progressive cancer, and rose in parallel to cancer progression in 29. Thus, serum CEA within or slightly above the normal range was 88% predictive that the patient might be free of disease or in remission; whereas elevated or rising level indicated disease progression. Accordance between serum CEA and clinical status occurred in 145 of 157 (92%) patients.
Serum levels of ovarian carcinoma antigen (CA 125) and breast carcinoma antigen (CA 15.3) were determined in 237 patients with breast carcinoma, 121 before any therapy and 116 after initial treatment, during uneventful follow-up or at the time of relapse. The aim was to assess how often the CA 125 test failed, i.e., was false-negative inpatients in whom the CA 15.3 test was true-positive and, more important, whether it gave diagnostic information in patients in whom the CA 15.3 test failed. Before surgery or other initial therapy, serum CA 125 and CA 15.3 gave similar information in 85.1 percent of the patients: true-positive in 4.1 percent and false negative in 81.0 percent; CA 125 gave less information in 13.2 percent; and more information in only 1.7 percent. During follow-up, serum CA 125 and CA 15.3 gave similar information in 73.3 percent of the patients: true-positive (i.e., rising persistently from a nadir or elevated above 65 U/ml) in 23.3 percent, true-negative in 36.2 percent, and false-negative in 13.8 percent; CA 125 gave less information in 25.0 percent: false negative in 22.4 percent and false-positive in 2.6 percent; and more information in only 1.7 percent. Therefore, the CA 125 test appears useless for staging and is redundant when the CA 15.3 test is employed, for management of patients with breast cancer.
Serum levels of carcinoembryonic antigen (CEA) and breast carcinoma antigen (CA 15.3) were determined in patients with breast carcinoma: in 129 before initial surgical or nonsurgical treatment and in 134 afterwards. Before any initial treatment, CEA was elevated in 15% of patients with Stage IV disease and CA 15.3 was high in 11% with Stage III and 48% with Stage IV. While monitoring management active disease was associated with elevated serum CEA in 66% of the patients, with elevated CA 15.3 in 73% and with at least one of the markers elevated in 86%. Both tests had high specificity (93% and 98%). The rise in serum CEA and, even more so, of serum CA 15.3 roughly paralleled the increase in bulk of the tumor: from locoregional disease through metastases to the lungs, bones, lungs with bones, and liver. Decreases in the levels of serum CEA and CA 15.3 reflected response to therapy, increases in the level of at least one marker-treatment failure, and levels fluctuating above the normal range indicated stationary disease. During follow-up, the predictive value of a negative test (levels within the normal range), suggesting that the patient might be free of disease, was 61% for CEA alone, 67% for CA 15.3 alone, and 80% for the two tests combined. We conclude that an elevated serum level of only one of the markers was useful for staging, implying advanced disease. Determination of both markers jointly was useful for monitoring the effectiveness of the therapy and for follow-up aimed at detection of relapse.
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