T.ance of the Roche Z-gel radioimmunoassay

Transcription

1 THE USE AND ABUSE OF CEA TEST IN CLINICAL PRACTICE WILLIAM R. MEEKER, JR., MD Charts of 7 patients having plasma carcinoembryonic antigen determinations during the period January 1, 17 through April 0, 17 were reviewed to determine whether CEA results led to clinical decisions altering management patterns. Data analysis disclosed that CEA test results did not result in any change in management in 17 patients with nonneoplastic disease. Most had single determinations. In 70 patients with neoplastic disease, CEA results led to changes in management in one patient with lung cancer and two patients with colon cancer, which may have altered prognosis. In a fourth patient, CEA results led to discovery of unresectable pancreatic cancer at laparotomy. Cost benefit analysis indicated a CEA test cost of $5,07.50 per patient benefitted in patients eligible for analysis. We conclude that maximal benefit to the patient results from serial CEA test use in followup of colon cancer patients after curative therapy. Cancer 1:858, 178. E REAGENTS NECESSARY FOR THE PERFORM T.ance of the Roche Zgel radioimmunoassay of plasma carcinoembryonic antigen (CEA) have been licensed commercially and the CEA assay has been widely applied. A collaborative study evaluating the clinical usefulness of the CEA assay by the Zgel method involving 5,000 plasma samples from more than 10,000 patients and healthy subjects from approximately 100 institutions led to the conclusion that the test is of value as an adjunct in the diagnosis and management of patients with neoplastic disease, especially when the values are obtained from a series of specimens and show a consistently increasing or decreasing level. The CEA test was not recommended for use as a screening test to detect cancer in the general population. Galen and Gambino analyzed the data from the Roche collaborative study to evaluate the sensitivity, specificity, and predictive value of the CEA test. They concluded that the data obtained in the Roche study failed to support any widespread usefulness for this test. Their evaluation disclosed the CEA test to be relatively insensitive to colon cancer and too sensi tive to other diseases, associated with an unacceptably high positivity level in nonmalignant diseases, and having a predictive value of only 7% under idealized conditions of high prevalence and total absence of any other disease or condition. Most of the reported clinical studies of CEA have been concerned with correlations between serum CEA concentrations and the clinical status of the patient.17 Moreover, most of these studies were done prior to FDA approval of the CEA test and clinical decisions could not be based on test results. Although these data have been important in defining the role of the CEA test in patient management, it is clear that the ultimate role of the CEA test in clinical practice remains to be established. This retrospective analysis of a single institution s experience with the CEA assay has as its objective the determining of whether the use of the CEA test led to clinical decisions which altered patient management patterns. Having obtained this information, we hope to define more precisely, those areas in patient management where the CEA test has a clearcut role. From the Department of Surgery, University of Kentucky Medical Center, Lexington, Kentucky 050. Address for reprints: Dr. William K. Meeker, Jr., Room C0, University of Kentucky Medical Center, 800 Rose Street, Lexington, Kentucky 050. The author thanks Mrs. Vi Kiviniemi and Mrs. Winifred Meeker for their assistance in data collection and analysis. Accepted for publication August 17, X PATIENTS AND METHODS Four hundred and sixtyeight patients registered at the University of Kentucky Medical Center had CEA determinations performed during the period from January 1, 17 through April 0, 17. Charts of four hundred American Cancer Society

2 No. USE OF CEA TEST Meeker 855 thirtyseven (%) of these patients were available for review. In many instances, these patients had additional CEA tests performed either prior to or following the CEA test which led to the patient s inclusion in the study. These additional CEA test results, when added to the four hundred and thirtyseven index test results, totaled 108 CEA tests. Data from all 108 tests were included in the data analysis reported herein. Charts were reviewed and the following information was abstracted onto data sheets: 1) Patients age, sex, and race, ) Medical diagnoses and dates, ) Cancer diagnoses and dates, ) Cancer therapy and dates, 5) Cigarette smoking history, ) History of alcohol intake, 7) Histologic diagnosis of cancer, 8) Stage of cancer, ) CEA results and dates, and 10) Evidence of clinical utilization of CEA test results. Four purposes of data analysis, the patients were ranked by decades with respect to age, and racially were categorized into Caucasian, Negro, Oriental, American Indian, and other groups. Medical diagnoses were classified into several categories to aid in data analysis. A category of diagnostic workup was utilized to classify those cases who were being worked up for symptomatology (frequently related to the digestive system) without a clear cut diagnosis being established. Other patients, who had a diagnosis or diagnoses established, were placed into categories representing the organ system predominantly involved; i.e., gastrointestinal, pulmonary, breast, gynecologic, etc. In patients having a cancer diagnosis, the malignancy was classified according to the organ system involved and the histology. Therapy was classified according to the modality used, as well as the inclusive dates of therapy. Therapeutic categories were surgery, radiotherapy, chemotherapy, and other. Cigarette smoking data were broken down into the following categories: undetermined, nonsmoker, smoker of unknown amount, and smoker of known amount. In this latter group, smoking was quantitated by pack/ years (number of packs/day X number of years smoked). Drinking history, if available, was sufficient to permit classification as nondrinker, social drinker, or alcoholic. The histology was obtained from the pathology report when available; otherwise, it was obtained from the physician s history. From information present in the charts, it was possible to stage malignant neoplasia into localized, regional spread, and distant metastasis categories. CEA results, when multiple, were grouped into time sequence for TABLE 1. Nonneoplastic Disease Categories Gastrointestinal disease 7 Diagnostic workup Renal disease 5 Vascular disease 0 Neurologic disease 15 Pulmonary disease 1 Miscellaneous disease* 1 TOTAL 17 *Collagen (), breast (), GYN (), diabetes (), dental (l), morbid obesity (l), inguinal hernia (1). the purpose of determining whether they were pretreatment tests, post treatment tests, or both. Finally, judgement was made concerning the reason why physicians in charge of the patient s care ordered the CEA test, and when the CEA test results led to any alteration in patient management. These judgements were based on information obtained from review of the patient s chart. RESULTS Patient Population The patient population could be divided into two broad groups based on diagnostic category. The first consisted of 17 patients (8% of total) having nonneoplastic disease diagnoses. The second consisted of 70 patients (% of total) having neoplastic disease diagnoses. Table 1 shows a breakdown of organ systems involved with the major diagnosis. Most patients had multiple diagnoses, but only the diagnosis which necessitated the hospitalization is considered in this table. As might be expected in a population of patients having CEA tests performed, the majority had disorders involving the gastrointestinal tract. The largest number of patients in this group had gastric ulcers, followed by patients with inflammatory bowel disease, biliary tract disorders, and functional bowel disorders. A large number of patients were undergoing diagnostic workups for multiple complaints without a firm diagnosis being established; these were placed in a diagnostic workup category. The renal disease diagnostic category included twentytwo patients with kidney transplants. These patients will be excluded from data analysis concerning effect of CEA test results on patient management, since they were the subjects of a special study being conducted by the renal medicine service. Patients classified under the pulmonary disease category had chronic obstructive airways disease in a majority of instances.

3 85 CANCER March 178 Vol. 1 Benign tumors Suspected malignancy Proved malignancy TOTAL TABLE. Neoplastic Disease Patients with neoplastic disease could be subdivided into three groups (Table ). The first group consisted of nine patients with benign tumors. Five patients had benign colonic polyps, and one patient each had a lipoma of the colon, a benign hepatic adenoma, a serous cystadenoma of the ovary, and a uterine fibroid. The second group consisted of ten patients with clinical pictures suspicious of malignancy which was histologically never confirmed. The site of malignancy was thought to be the liver in three, the stomach in two, the pancreas in two, and the breast, kidney, and ovary in single patients. CEA values greater than 5 ng/ml were noted in seven of these patients and in four were greater than 0 ng/ml. The largest group of patients with neoplastic disease was comprised of 51 patients having histologically documented malignancy. In Table they are further subdivided into the organ system involved. The largest group was gynecologic malignancy, and cervical cancer constituted a majority (8%) of diagnoses in this group. The remainder were divided among ovarian cancer, endometrial cancer, vulvar cancer, and cancer of the vagina. Since many of these patients have been part of ongoing studies previously reported by members of the gynocologic ~ervice~~ *~ ~ they will be excluded from analysis of effect of CEA test results on patient management. Gastrointestinal malignancy, the next most common group, consisted primarily of colon and rectal cancer (8%) with the remainder consisting of pancreas and stomach cancer. Multiple primary malignancies included ten metachronous cancers and four synchronous cancers. The metachronous cancer group contained four patients with squamous carcinomas of the cervix and adenocarcinomas of the breast, Gynecologic Gastrointestinal Breast Multiple primaries Miscellaneous Lung Metastatic (occult primary) Genitourinary TOTAL TABLE. Proved Malignancy TABLE. Age Agerange >80 Nonneoplastic 5(7%) 58(%) 1(7%) (%) diseases Neoplastic 5(1%) 1(5%) 85(1%) 8(%) diseases two with squamous carcinomas of the lung and cervix, and one each with squamous carcinoma of the lung and adenocarcinoma of the breast, squamous carcinoma of the cervix and adenocarcinoma of the endometrium, adenocarcinoma of the colon and breast combine with squamous carcinoma of the vulva. The synchronous group consisted of a single patient with double colon primaries together with a primary breast cancer and single patients with squamous carcinoma of both lung and cervix, adenocarcinoma of the endometrium and arrhenoblastoma of the ovary, and medullary carcinoma of the thyroid and pheochromocytoma of the adrenal gland (Sipple s syndrome). The miscellaneous group consisted of five patients with head and neck cancers ( squamous carcinomas, 1 melanoma, 1 osteosarcoma), five with skin cancers ( melanomas, basal cell carcinomas, 1 squamous carcinoma), two with Hodgkin s disease, one with histiocytic lymphoma, and one with leiomyosarcoma of the duodenum. The group classified as metastatic (occult primary) included three patients with liver metastasis, one with brain metastasis, one with bone metastasis, and one with skin metastasis. Comparison of Patient Populations Patients having nonneoplastic disease diagnoses were compared to those having neoplastic disease diagnoses with respect to age, sex, race, cigarette smoking, alcohol consumption, CEA levels and the pattern of CEA values. Age and cigarette smoking, as well as alcohol intake, are known to influence CEA levels. Table summarizes the data on age. No pediatric age group (less than 1 years) patients were included. Relatively more patients in the 10 age group were present in the nonneoplastic disease category than in the neoplastic disease category. The neoplastic disease category had a higher percentage of patients in the 10 age group than the nonneoplastic disease category. There were similar percentages of patients in the over 0 age categories. Overall, these differences would tend to favor higher CEA levels in the neoplastic disease group.

4 Nu. USE OF CEA TEST Meeker 857 TABLE 5. Sex and Race Male Female Caucasian Negro Oriental Nonneoplastic disease 87(5%) 7(7%) 1(8%) 17(10%) 1(1%) Neoplastic disease 5(1%) 81 (81%) (0%) ( 10%) Distribution of patients by sex and race is given in Table 5. It indicates a preponderance of males in the nonneoplastic disease group and of females in the neoplastic disease group. This latter finding is explained by the inclusion of a large group of patients with gynecologic cancers in the neoplastic disease group. In both groups there was an approximate :l ratio of Caucasians to noncaucasians, which reflects the racial distribution of the hospital population from which the patients were drawn. The proportion of cigarette smokers to nonsmokers is given in Table. Unfortunately, a quarter of the charts in the nonneoplastic category and slightly more than a third of neoplastic disease charts lacked information regarding cigarette use. However, in the remainder, sufficient information was available to categorize patients as nonsmokers or smokers. The nonneoplastic disease category contained a higher percentage of smokers than the neoplastic disease category and in those patients whose smoking could be quantitated into pack/years, there were more in the nonneoplastic disease category who smoked more than 11 pack/years than in the neoplastic disease category, suggesting a preponderance of heavy smokers in the former. This observation probably explains the approximately equal percentages of CEA values in the 510 ng/ml range for nonneoplastic and neoplastic groups (see Table 8). Table 7, which provides information regarding alcohol consumption in the two groups, may also help explain the surprisingly high percentage of CEA values in the 510 ng/ml range. Again, no information was available in slightly more than one quarter to one third of cases. In the remainder, however, there is a clearcut preponderance of social drinkers and alcoholics in the nonneoplastic disease category. Goldenberg has presented data showing that 5% of patients with alcohol addiction, in a collected series from the literature, had CEA levels above. ng/ml and furthermore, that a majority of these were in the.5.0 ng/ml range. The unequal distribution of drinkers (and smokers) would tend to favor higher CEA values in the nonneoplastic diseases group. Table 8 summarizes the CEA values in patients with neoplastic compared with nonneoplastic disease. A higher percentage of patients with nonneoplastic disease diagnoses had CEA values less than 5 mg/ml than did patients with neoplastic diseases. As noted previously, almost equal percentages of patients in both diagnostic categories had CEA values in the 5 10 ng/ml range, whereas five times more patients with neoplastic disease diagnoses had CEA values greater than 10 ng/ml than patients with nonneoplastic disease diagnoses. These data parallel earlier published data from the University of Kentucky. Most CEA values in the 510 ng/ml range in patients with nonneoplastic disease occurred in patients with chronic obstructive airways diseases, inflammatory bowel disease, liver disease, and peptic ulcer disease. A single CEA value in the nonneoplastic group which was in the 5000 ng/ml range occurred in an elderly male patient who died before the clinicians received the CEA report. Since no autopsy was permitted, the possibility of an occult cancer cannot be ruled out. Perhaps the most significant difference between the two groups was in the pattern of CEA assays (Table ). Patients with nonneoplastic disease had single determinations performed 5% of the time, while patients with neoplastic disease had multiple determinations performed % of the time. This undoubtedly reflects the purpose for which the CEA test was performed. In patients TABLE. Cigarette Smoking Undeter Non Smoker (pack/years) mined smoker Unknown Nonneoplastic 1 5 n(1)* 17() 15() () Neoplastic 8 8 1() 0(0) 7(1) 1 l() * Figures in brackets refer to percentage of smokers for whom quantitative data IS available.

5 858 CANCER March 178 Val. 1 TABLE 7. Alcohol Consumption Undetermined Nondrinker Social drinker Alcoholic Nonneoplastic 7(8%) 77(%) (17%) 1(%) Neoplastic 7(%) 10(5%) 5(%) 8(%) with nonneoplastic disease, a majority of tests were performed as diagnostic or screening procedures to rule out cancer. In patients with malignant neoplasia (exclusive of gynocologic cancer), especially those with histologic documentation, a majority had tests performed for followup or a combination of diagnosis and prognosis (Table 10). Clinical Utilization of the CEA Test in Nonneoplastic Diseases, Benign Tumors, and Suspected Neoplasia In assessing the reason why clinicians ordered the CEA test in patients with nonneoplastic diseases, it appeared that a desire to rule out cancer was the prime motivation; however, it was rare to find an acknowledment of this fact in the chart. In patients with suspected neoplasia, not histologically documented diagnostic considerations also appeared to be the primary motivation for CEA test utilization, and indeed, seven of the ten patients had CEA values greater than 5 ng/ml with one patient having a CEA value of 10 ng/ml! Finally, in those patients with benign tumors, the CEA test was utilized primarily for diagnostic purposes, and was less than.5 ng/ml in a majority. In assessing whether the CEA test results led the clinician to alter patient management in any way, we were unable to find any impact of the CEA test on clinicians behavior. Clinical Utilization of the CEA Test in Proved Malignancy In considering histologically documented malignancy, it is important to provide information regarding histology, stage of disease, and therapy utilized in order to understand the context in which the CEA test was used. Table 11 summarizes data regarding histology. A majority of the patients with proved malignancy had adeno TABLE 8. CEA Values carcinomas. At the individual sites studied, this was true in most instances with the exception of the miscellaneous group, and the lung cancer group, where squamous and other histology were frequent. In grouping the different sites by stage of disease (Table 1) the patients with regional spread of their cancers and patients with distant metastases were the most frequent and present in approximately equal percentages. With respect to primary therapy (Table 1) a small minority had no treatment. Most of these patients were those with histologically proven malignancy from a clinically occult primary. It is particularly difficult to understand why CEA tests were ordered in this group of patients. The most frequent therapeutic modality used was surgery, with or without adjuvant radiotherapy or chemotherapy followed by primary radiation therapy, chemotherapy, and other modalities in descending order of frequency. The other modality category represented hormone therapy of breast cancer. In two types of proved malignant neoplasia, the CEA test was used extensively for purposes of followup. These were col onrectal cancers and breast cancers. No formal protocol for CEA test use was followed by physicians managing colonrectal cancer and breast cancer patients. In order to determine if there were differences in the type of followup being applied to these cancer types (which might account for any difference in frequency of physicians management changes based on CEA test results) the two groups were analyzed to determine average number of CEA s per patient, average months followup per patient, and average interval between CEA tests (Table 1). It can be seen that differences existed between the two groups with the colonrectum group having the closest followup. However, the differences were not marked, so that frequency of followup does not TABLE. Pattern of CEA Values <5 510 >10 Total ng/ml ng/ml ng/ml Single determination Multiple determinations Nonneoplastic 17 1(8%) (1%) (%) Neoplastic 70 18(8%) 5(17%) 1(15%) Nonneoplastic 15(5%) 8(5%) Neoplastic (%) 177(%)

6 ~ No. USE OF CEA TEST Meeker 85 TABLE 10. Purpose of the CEA Test in Patients with Malignancy Diagnosis/ Total Prognosis Followup Both Unknown Gastrointestinal Breast Multiple Primaries hiiscellaneous Lung Metastatic (occult primary) Genitourinary TOTAL (%;I) (1) (51) 8(0) 7 1 1(1) appear to be a significant variable influencing physicians changes in management. When patients with histologically proved malignancy were evaluated to determine if CEA test results had influenced patient management, only four patients could be found where patient management had clearly been altered by CEA test use. Clinical data from these patients are summarized in Table 15. In two instances (cases 1 and ) where the CEA test was utilized for diagnostic purposes, elevated values led clinicians to explore the possibility of malignancy more thoroughly than they otherwise might have done. In one of the patients, a potentially curative resection of a lung cancer was done, so that the CEA test result may have led to an alteration of the patient s prognosis. In the other patient, staging at the time of laparotomy confirmed, the incurability of the patient s pancreatic cancer. In two patients with colonrectal cancer, serial CEA test results suggested recurrence during the followup period. In one, the CEA results led to potentially curative resection of a recurrent cecal cancer, thus possibly altering the patient s prognosis. In the Other patient, reexploration, after one year of adjuvant weekly 5fluorouracil therapy, failed to confirm the presence of residual cancer. Although valuable prognostic information was gained, the procedure itself did not alter prognosis. DISCUSSION CostBenefit Analysis The cost of a laboratory procedurerelative to its benefit to the patienthas become an important consideration in the utilization of such tests. The cost of a single CEA test in our hospital is $0.00. Since 7 CEA tests were performed in patients (excluding those with renal transplants and gynecologic cancer) the cost of CEA tests was $0,10.00 in this patient population. If we consider the four patients in which the CEA test led to an alteration in patient management as benefitted * by the use of the test, then the cost of the CEA test per patient benefitted is $5, This figure could be considerably reduced by restricting the use of the CEA test. From the results of two cooperative trials of the CEA test carried out in a number of centers in the United States and Canada, as well as the reported expe * For those unwilling to accept this definition of benefit, the cost of the CEA test in the three patients whose prognoses were altered by the CEA was $, TABLE 11. Histology of Proved Malignancy* Adeno Total carcinoma Squamous Other Unknown Gastrointestinal 51 Breast Xlultiple primaries 1* Miscellaneous 1 Lung 10 Metastatic (occult primary) Genitourinary TOTAL^ * Excluding gynecologic malignancy. 1 Total includes more than one histologic type

7 80 CANCER March 178 Vol. 1 TABLE 1. Stage of Proved Malignancy* Total Insitu Local Regional Distant Unknown Gastrointestinal 51 Breast Multiple primaries 1 Miscellaneous 1 Lung 10 Metastatic (occult primary) Genitourinary TOTAL (W) (18) 7(5) () 17( 1.5) * Excluding gynecologic malignancy. rience of a number of individual institutions, it is clear that currently available CEA tests cannot replace any of the now standard diagnostic techniques for cancer detection'; however, its use for assessment of therapy in selected patients or for followup of patients known to be at high risk for recurrence appears to be promising. Mach et al.,' Herrera et al.,' and Sugarbaker et al.," have shown that elevated CEA values often precede other clinical signs of colon cancer recurrence. This would give the clinician a lead time of 10 months according to Mach et al.,g or a mean lead time of around months according to Herrera et a1.' Many patients with recurrence are incurable, by present day therapy, because of widespread metastatic disease; however, Rieger and Wahren" have pointed out that 70% of 0 patients with local recurrence without distant metastases, who were potential candidates for a reoperation for cure, had raised plasma CEA values. This gives the CEA assay a better than expected usefulness in the clinical followup situation. If the CEA test in our hands has been restricted to the 51 gastrointestinal cancer patients in whom CEA tests were performed, two patients would have benefittedin the sense of a potential improvement in prognosisfrom the use of the CEA test, and the costbenefit ratio would have been reduced to $,0.00 per patient benefitted. Ultimate Role of CEA Test in Clinical Practice Although the CEA test aided in the diagnosis of lung cancer and a pancreatic cancer in our patient population, the experience of other investigators would suggest that the CEA assay is not selective or specific enough at this time, to be used for screening purposes for lung' or pancreatic" cancer. The CEA test does, in the hands of most investigators, appear to have value as a prognostic marker, capable of suggesting the successful resection of a tumor and in detecting recurrence at an earlier time than might be possible with more conventional diagnostic tests. Our experience with breast cancer supports the experience of Chu and Nemoto' who found the CEA test to be of little value in the followup of breast cancer patients. We would, therefore, recommend that the CEA test be limited to the monitoring of patients with colon and rectal cancer. Martin et al.'' have attempted to refine the CEA test for use in early detection of potentialy resectable recurrence. They have determined TABLE 1. Primary Therapy of Proved Malignancy Total None Radiation Surgery* Chemo Other Unknown Gastrointestinal 51 5 Breast 1 5 Multiple primaries 1 8 Miscellaneous Lung Metastatic (occult primary) 1 1 Genitourinary 1 1 TOTAL (%) 15 8() 1(1) (71) 8() () 1(1) * With or without radiation and/or chemotherapy,

8 No. USE OF CEA TEST Meeker 8 1 TABLE 1. Followup Data Avg. Avg. interval Number Avg. no. Months (mas.) of CEA's/ Followup/ between patients Patient Patient CEA's Colon 5.(18) 1.8( 1).(0.5.5) Rectum Breast 1.(7) 1.5().5(.07.0) and grouped interassay and intraassay accuracy as a CEA nomogram which measures the observed CEA level against the 5% confidence limits for that observation. The CEA nomogram can be used to identify statistically significant increases of small magnitude. In their hands, the use of this nomogram permitted the correct identification of tumor recurrence in of 5 patients who underwent reoperation. Unfortunately, only patients had localized recurrence amenable to curative resection. It is clear that intelligent use of the CEA test at the present time should be directed toward the identification of potentially curable recurrence. Polk and Spratt1 have stated this most clearly as follows: "Thus, in our opinion aside from evaluation of new theoretical schemes, there is no indication for continued followup of patients whose colorectal carcinomas were resected for cure unless one is seeking recurrent disease which is limited sufficiently to allow retreatment. " These investigators have presented a followup scheme based on data of interval recurrence rates suggesting that followup examinations be performed about every two months in the first postoperative year, every three months in the second year, every six months in the third and fourth years, and annually thereafter. They calculated that the economic yield of the followup schedule and use of resection when indicated, based on available data, would result in a saving of $7,000 in a theoretical population of 1,000 patients initially resected for cure. Martin et a1.l' have proposed a CEA protocol which involves use of periodic CEA levels determined every month during the first postoperative year, every two months for the second and third postoperative years and every three months for two years. The application of such a scheme of periodic CEA tests (or its mofification to fit the followup scheme of Polk and Spratt1) to a patient population having characteristics identifying them as likely to have local recurrence (as defined by these latter investigator^'^) appears to be the most logical use of the CEA test at the present time. Neville" has suggested an additional refinement, which is the use of a further test in association with the CEA test, which would help to discriminate between elevated CEA levels due to liver metastases and those at other sites. The serial assay of plasma CEA and gamma glutamyl transpeptidase (GGT) appears, in his hands, to accomplish this purpose. If one could use the CEA test to accurately pinpoint the patients developing locally recurrent cancer prior to the appearance of other clinical parameters, there is every expectation that the cure rates of reexploration reported by Polk and Spratt1 could be significantly improved upon. Clinical trials to evaluate this possibility are urgently needed. TABLE 15. Patients whose Management was Altered by CEA Test Result No., Service Age Race Sex Diagnosis Circumstance 1. Medicine 8 White Female Adenocarcinoma of lung. Surgery 5 White Male Adenocarcinoma of pancreas. Surgery 58 White Female Adenocarcinoma of colon. Surgery Negro Female Adenocarcinoma of colon CEA result led to discovery of solitary pulmonary nodule, on review of chest xrays, which was resected for cure. Elevated CEA suggested pancreatic cancer in patient with low back pain and led to confirmation at laparotomy of unresectable cancer Rising CEA levels during postoperative adjuvant chemotherapy led to negative reexploration Rihg CEA levels in patient with blood loss anemia and otherwise negative workup* after colectomy led to reexploration and curative excision of local recurrence * Including upper GI series and barium enema

9 8 CANCER March 178 Val. 1 REFERENCES 1. Alexander, J. C., Silverman, N. A,, and Chretien, P. B.: Effect of age and cigarette smoking on carcinoembryonic antigen levels. JAMA 5:17517, 17.. Chu, T. M., and Nemoto, T. : Evaluation of carcinoembryonic antigen in mammary carcinoma.. Natl. Cancer Inst. 51 :11111, 17.. Donaldson, E., Van Nagell, J. R., Jr., Wood, E. G., Pletsch, Q,, Goldenberg, D. M. : Carcinoembryonic antigen in patients treated with radiation therapy for invasive squamous cell carcinoma of the uterine cervix. Am.. Roentgenol. 17:881, 17.. Galen, R. S., and Cambino, S. R.: Letter to the editor. Hum. Pathol. :1810, Go, V. L. W. : Carcinoembryonic antigen, clinical application. Cancer 755, 17.. Goldenberg, D. M.: Oncofetal and other tumorassociated antigens of the human digestive system. In Current Trends in Pathology, vol, B. C. Morson, Ed. Berlin, Springer Verlag, 17; pp Hansen, H. J., Snyder, J. J., Miller, E., Vandevoorde, J. P., Miller, 0. N., Hines, L. R., and Burns, J. J.: Carcinoembryonic antigen (CEA) assay. A laboratory adjunct in the diagnosis and management of cancer. Hum. Pathol. 5:1 17, Herrera, M. A., Chu, T. M., and Holyoke, E. D.: Carcinoembryonic antigen (CEA) as a prognostic and monitoring test in clinically complete resection of colorectal carcinoma. Ann. Surg. 185, 17.. Mach, J. P., Jaeger, P., Bertholet, M. M., Ruegsegger, C. H., Loosli, R. M., and Pettavel, J.: Detection of recurrence of large bowel carcinoma by radioimmunoassay 01 circulating carcinoembryonic antigen (CEA). Lancet :55 50, Martin, E. W., Jr., James, K. W., Hurtubise, P. E., Catalano, P., and Minton, J. P.: The use of CEA as an early indicator for gastrointestinal tumor recurrence and secondlook procedures. Cancer :0, Meeker, W. R., Jr., Kashmiri, R., and Hunter, L., Clapp, W., Griffen, W. 0.: Clinical evaluation of carcinoembryonic antigen test. Arch. Surg. 107:7, Neville, A. M.: The role of carcinoembryonic antigen (CEA) in the early detection of cancer. In Health Control in Detection of Cancer, H. Bostrom, Ed. Stockholm, Almquist and Wiksell, 17; pp Ona, F. Zamcheck, N. Dhar, P., Moore, T. L., and Kupchik, H. Z.: Carcinoembryonic antigen (CEA) in the diagnosis of pancreatic cancer. Cancer 1 :7, Polk, H. C., Jr., and Spratt, J. S.: Recurrent colorectal carcinoma: detection, treatment and other considerations. Surgery :, Rieger, A., and Wahren, B.: CEA levels at recurrence and metastases; important for detecting secondary disease. Scand.. Gastroenterol. 10:887, Sugarbaker, P. A., Zamcheck, N., and Moore, F. D.: Assessment of serial carcinoembryonic antigen (CEA) assays in postoperative detection of recurrent colarectal cancer. Cancer 8:1015, Terry, W. D., Henkart, P. A,, Coligan,, J. E., and Todd, C. W. : Carcinoembryonic antigen: characterization and clinical applications. Transplant Rev.: 1001, Van Nagell, J. R., Jr., Meeker, W. R., Jr., Parker, J. C., and Harralson, J. D. : Carcinoembryonic antigen in patients with gynecologic malignancy. Cancer 5:1717, Van Nagell, J. R., Jr., Meeker, W. R., Jr., Parker, J. C., Kashmiri, R., and McCollum, V.: Carcinoembryonic antigen in intraepithelial neoplasia of the uterine cervix. Am.. Obstet. Gynecol. 1:lOS10, Vincent, R. G., Chu, T. M., Fergen, T. B., and Ostrander, M. : Carcinoembryonic antigens in 8 patients with carcinoma of the lung. Cancer :007, 175.