Serial Carcinoembryonic Antigen Determinations Research Articles

Cystadenocarcinoma of the pancreas: Neo‐adjuvant therapy and CEA monitoring

Cystadenocarcinoma of the pancreas is generally considered to be unresponsive to chemotherapy and radiation therapy. We present two cases of laparotomy-proven unresectable cystadenocarcinoma which responded to intravenous 5-fluorouracil (1,000 mg/m2/24 hr x 5 days x 2) and 4,000 rads of radiation therapy. Both patients had objective response with marked shrinkage of the tumor as determined by clinical examination and computed tomography. At reexploration both tumors had become completely resectable with histologically clear margins and negative lymph nodes. Carcinoembryonic antigen (CEA) levels were elevated in both patients at initial presentation (86 and 71 ng/ml). The CEA levels declined to 19.9 and 66.0 ng/ml, respectively, after neo-adjuvant therapy, and both fell to normal levels after resection. Although surgical resection has been considered the only curative therapy for patients with pancreatic cystadenocarcinoma, we suggest that preoperative irradiation and chemotherapy may reduce the size of seemingly unresectable tumors. We also recommend serial CEA determinations in patients with levels initially elevated as a marker of the response to neo-adjuvant and operative therapy.

Carcinoembryonic antigen (CEA) and alkaline phosphatase in progressive colorectal cancer with special reference to patient survival

The prognostic value of serial CEA tests was evaluated in 175 consecutive patients with progressive colorectal cancer who subsequently died of their disease. The upper normal plasma CEA limit was determined to be 8 ng/ml from serial CEA determinations in 31 patients radically operated on for colorectal cancer and observed in median 40 months without evidence of recurrence. A CEA value of >8 ng/ml was highly suggestive of residual disease or recurrence, even when no clinical evidence was present. Approximately 90% of the patients dying from colorectal cancer showed an increase in CEA to >8 ng/ml during the course of the disease. In 63% of the patients CEA increase preceded clinical progression or relapse, with a median time period of 4 months. Sixty-eight per cent of the patients had rising CEA values over an extended time period of many months, 14% had a preterminal increase, 13% had constantly normal and 5% constantly elevated CEA. As 6 9 patients developed a drop in CEA in relation to initiation of chemotherapy without clinical response, it is concluded that CEA is not a reliable indicator of clinical response to chemotherapy. Patients with liver metastases had higher CEA and alkaline phosphatase levels than patients with only localized disease. However, no good statistical correlation between CEA and serum alkaline phosphatase was found in patients with liver metastases (coefficient of correlation r = 0.35). An increase in CEA from normal to above 8 ng/ml predicted a decrease in survival time of median 60% counted from the time of diagnosis. The numerical CEA value was predictive of shortening of survival only when greater than 3000 ng/ml. Such high values were observed only in a minority of the patients (12%). Greater than 1000 U/l (27% of the patients) alkaline phosphatase predicted an extremely poor prognosis, with a median survival of 1 month (range 0.5–4 months). It is concluded that a rise in CEA to >8 ng/ml indicates with high degree of certainly relapse or disease progression in colorectal cancer patients. CEA is not a reliable indicator of clinical response to chemotherapy, and an increase in the CEA level is of little prognostic value concerning survival. Alkaline phosphatase seems to be a more valuable predictor of a worsening of prognosis.

Diagnostic and Prognostic Values of Carcinoembryonic Antigen in Medullary Carcinoma of the Thyroid*

This study was conducted to compare the diagnostic and prognostic values of calcitonin (CT) and carcinoembryonic antigen (CEA) measurements in patients with medullary carcinoma of the thyroid (MCT). Plasma CEA, basal CT (BCT), and peak CT (PCT) levels after pentagastrin stimulation were determined in 15 patients with occult familial MCT before treatment. CEA was elevated in 11 patients (73%), BCT in 8 patients (53%), and PCT in all patients. The prognostic values of serial CEA and BCT determinations were studied in 24 other MCT patients followed for a period of 1.5-8 yr. These patients were divided into 2 groups; group I consisted of 11 patients with normal serial CEA levels, and group II consisted of 13 patients with persistently elevated CEA levels. In group I, 2 patients (18%) developed metastases compared with 10 patients (77%) in group II (P less than 0.001). Elevated BCT levels were found in all patients with metastases as well as in 63% of patients with no evidence of disease. When CEA time curves were studied, three patterns could be identified: 1) a steep slope with rapidly rising CEA levels in patients with rapidly progressive disease, 2) a flat slope in patients with no metastasis or nonprogressive disease, and 3) an intermediate type of slope in patients with slowly progressive disease. Slope analysis of BCT time curves was not done because of marked fluctuations in BCT levels. PCT after pentagastrin stimulation remains the best diagnostic marker for MCT. However, CEA may be a better prognostic indicator, as it discriminated more efficiently between patients with and without metastasis. Slope analysis of CEA time curve and calculation of the doubling time are recommended, as they correlated well with the course of the disease.

Assessment of serial CEA determinations in urine of patients with bladder carcinoma.

Carcinoembryonic antigen (CEA) levels in urine and serum from 294 patients with bladder cancer in varying stages have been clinically evaluated. All urine samples were obtained from patients with intact renal function and without bacterial infection in the bladder. The samples were collected before, during, and at follow-up examination after radiotherapy. They were perchloric acid extracted before being assayed in a double-antibody radioimmunoassay. The geometric mean of urine CEA levels for patients with primary tumors of Stage T1 or T2 was significantly lower than that for those with Stage T3 or T4 disease. The urine CEA levels for patients with tumors of various histologic grades did not differ. The urine CEA levels decreased from before to after radiation treatment of the primary tumor. Patients with recurrence within six months after undergoing primary treatment had higher initial mean urine CEA levels than did those without evidence of recurrence. The prognostic information for recurrence was limited to the more advanced tumors. Differences were also found between the means of samples taken before recurrence and after treatment of recurrent tumors; with regression of the tumor, a lower mean urine CEA level was found; with progression, a higher value. Urine CEA levels before any treatment were higher when the patients had a short survival time. Serum CEA levels were not related to stage or grade of the primary bladder tumor but levels were slightly elevated with metastases. The determination of urine CEA levels seems to be useful in the follow-up of patients with bladder carcinoma because when initially high, it adds to the information of the T classification and predicts early recurrence, and the monitoring of individual patients after primary treatment is useful for detecting recurrence.

Serum CEA monitoring in the follow-up of colorectal cancer patients with negative preoperative serum CEA

Thirty-nine patients with colorectal cancer and normal preoperative levels of carcino-embryonic antigen (CEA) were followed up with serial CEA determinations and with complete clinical and laboratory work-ups for the detection of tumor recurrence, for at least 1 yr after surgery. The same schedule for serum CEA assay and other clinical and laboratory tests was followed, for comparison, in 32 colorectal cancer patients with elevated preoperative serum CEA titers, and in whom surgery had been followed by a return to normal of the CEA values. In the follow-up group with negative preoperative serum CEA values, 66.7% of the patients had normal serum CEA titers, and 60% were free from symptoms of tumor recurrence after 1 yr from surgery. Whereas, 28.2% of the patients of this group showed a steady rise of their serum CEA levels after periods ranging from 3–12 months from surgery; this serum CEA elevation preceded in nine of these patients other evidence of tumor recurrence by 3–5 months in the average. The above pattern was superimposable to that observed in the patients with positive preoperative serum CEA, about one third of whom exhibited a steady rise of serum CEA to abnormal values (as an early indicator of tumor recurrence) in the first year after surgery. The present results point out the relevant value of monitoring the serum CEA titers also in the postoperative follow-up of patients with normal preoperative serum CEA, since about one third of these patients may develop steadily rising serum CEA levels as an early indicator of tumor recurrence in the first year after surgical treatment.

Sixty second-look procedures indicated primarily by rise in serial carcinoembryonic antigen

Recurrent tumor was present at second-look operations in 56 of 60 patients (93.3%) reoperated upon during the past 7 years solely because serial carcinoembryonic antigen (CEA) values rose. Recurrent tumor was later identified in three of the remaining four patients; the fourth had severe liver disease and was undergoing hepatotoxic chemotherapy. Twenty-two patients were evaluated retrospectively; 38 patients entered in a protocol are termed prospective patients (60.5%). Delay between rise in CEA and reoperation in retrospective patients with unresectable tumor was 7 months, in contrast to 3.5 months in those with resectable tumor; while delay in prospective patients with unresectable tumor was 4.5 months and in those with resectable tumor only 1.5 months. Groups were similar according to Dukes' classification: B-7, C-14, D-1 (retrospective); B-10, C-26, D-2 (prospective). Serial CEA determinations every 6 weeks for the first 24 months detected recurrent tumor in 93.3% of patients. Incidence of resectable tumors increased when delay between rise in CEA and reoperation was shortened. Twenty-one patients (35%) remain disease-free, the longest time more than 7 years. One additional negative second-look patient is apparently free of tumor. No operative death has occurred, and major operative morbidity remains low (<10%).

Carcinoembryonic antigens (CEA) in patients with metastatic breast cancer under endocrine and therapeutic treatment (author's transl)

Carcinoembryonic antigen (CEA) was determined in 72 patients with metastatic breast cancer under various kinds of treatment. In 53 cases, CEA levels were elevated. They correlated with free interval, metastatic spreading, alkaline phosphatase (AP) and gamma-glutamyltranspeptidase (gamma-GT). Serial CEA determinations in 50 of the 72 patients revealed increased CEA levels in connexion with progressive tumour growth and decreased CEA levels in connexion with response to treatment. CEA may therefore be useful in helping to assess the extension of the tumour and the effect of treatment in patients with matastatic breast cancer.

Carcinoembryonic antigen (CEA) in patients with lung cancer: correlation with tumour extent and response to treatment (author's transl)

Carcinoembryonic antigen (CEA) was determined at the time of diagnosis in 90 patients with lung cancer. CEA levels were elevated in 47 (52%). High CEA levels were often associated with the presence of metastases. Serial CEA determinations in 40 patients, before and after radiotherapy and chemotherapy, revealed that patients who responded to treatment had a decreased CEA level, whereas those with progressive tumour growth had increased ones. CEA assay may, therefore, be useful in detecting metastases and in helping to assess the effect of treatment in patients with lung cancer.

The prognostic significance of carcinoembryonic antigen in the plasma and tumors of patients with endometrial adenocarcinoma

Carcinoembryonic antigen (CEA) levels in plasma and the immunocytochemical detection of tumor CEA were studied in patients with endometrial adenocarcinoma treated at the University of Kentucky Medical Center from 1973 to 1976. The incidence of CEA elevation in a group of 60 patients varied directly with uterine size, histologic differentiation, and stage of disease. Immunoperoxidase staining for CEA was performed on 42 specimens, and four were positive, indicating a tissue concentration of CEA of at least 5 μg per gram. Following operation, CEA levels returned to normal within eight weeks in all but two patients, both of whom were later shown to have persistent or recurrent cancer. These data suggest that serial plasma CEA determinations may be useful in predicting occult recurrence of endometrial cancer in patients in whom the plasma or tumor initially contains elevated concentrations of this antigen.

Carcinoembryonic antigen in osteosarcoma

Plasma carcinoembryonic antigen (CEA) assay was done in 30 patients with osteosarcoma. CEA was found positive (greater 2.5 ng/ml) in 17 of 21 patients who had active evidence of disease and negative (less than 2.5 ng/ml) in all 9 patients who were in complete remission resulting from previous amputation of chemotherapy. Serial CEA determinations demonstrated a fall to normal in 7 of 9 patients following successful surgery of chemotherapy and a ruse and fall (fluctuation) of levels in 8 patients who had tumor progression while on chemotherapy. Clinical recurrence of disease in two instances preceded or coincied with CEA elevation. The CEA assay in osteosarcoma although non-specific could be used as an inportant adjunct to experienced clinical judgment, periodic x-ray examination, and laboratory study to prognosticate the course of osteosarcoma during therapy. The interpretation of a rising or falling CEA titer alone, however, must be made with caution.

Assessment of serial carcinoembryonic antigen (CEA) assays in postoperative detection of recurrent colorectal cancer.

Monthly serial postoperative CEA determinations, three-monthly system review plus physical examination, and a battery of six-monthly laboratory and radiologic tests were compared in order to evaluate each in detection of recurrent colorectal cancer. Twelve of the 33 patients studied prospectively developed recurrent disease. In this study CEA was found not to be a substitute for careful clinical follow-up, but if used in a serial manner it was a useful adjunct for detection of early recurrent cancer, especially intra-hepatic and retroperitoneal disease recurring in patients with elevated pretreatment CEA levels. The other laboratory and radiologic tests employed were often useful to confirm progressing disease, but they did not reveal any first evidence of recurrent disease.

Usefulness of Serial Carcinoembryonic Antigen (CEA) Determinations in Monitoring Chemotherapy

Serial carcinoembryonic antigen (CEA) levels were measured during chemotherapy for metastatic cancer in 94 patients. Criteria for chemotherapy responses were those used by the Central Oncology Group. Patients were classified according to changes in CEA levels and response to chemotherapy. Four categories represented a positive correlation: (1) increasing abnormal CEA with progressing disease, (2) decreasing abnormal CEA with disease regression, (3) unchanged abnormal CEA with stable disease, (4) change from normal to abnormal CEA with progressive disease. Positive correlation of serial CEA levels with clinical responses occurred in 71% of patients with GI cancer, 51% with breast cancer, 42% with sarcoma, 50% with respiratory cancer, and 25% with melanoma. These data indicate that serial CEA determinations may be of value as an additional parameter of response to chemotherapy in gastrointestinal cancer.

Usefulness of serial serum carcinoembryonic antigen (CEA) determinations during anticancer therapy or long-term follow-up of gastrointestinal carcinoma.

Repeated determinations of serum CEA levels in untreated advanced gastrointestinal cancer patients with initially elevated values showed day to day variations of ±35%. If there was no intervening chemotherapy, all such patients who were followed over long term showed progressively increasing CEA levels. With chemotherapy there was a general correlation between changes in serum CEA levels and clinically measured changes in tumor mass. Among patients who showed objective improvement, 75% had reduction in serum CEA levels (> 35%) and 87% had either reduced or unchanged levels. Among those who showed objective progression, 65% had increases in serum CEA levels (> 35%) and 80% had either increased or unchanged levels. Paradoxical reductions in CEA levels were observed in some patients approaching terminal status. Among 80 patients being followed with serial CEA determinations after potentially curative resections of large bowel cancer and normal postoperative CEA levels, 6 have again showed clinical evidence of malignant disease and in 5 of these there was concurrent elevation of serum CEA. Serial serum CEA determinations appear to have some value for following the course of gastrointestinal cancer patients after surgery or chemotherapy, but these determinations must be interpreted in the context of the over-all clinical picture.