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Computed Tomography in Endometrial Carcinoma

From the Department of Obstetrics and Gynecology, Division of Gynecologic Oncology and the Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, Iowa City, Iowa.

Address reprint requests to: Joseph P. Connor, MD Department of Obstetrics and Gynecology University of Illinois at Chicago 820 South Wood Street, MC 808 Chicago, IL 60612-7313 E-mail: jconnor{at}uic.edu

	Abstract

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Objective: To determine the value of computed tomography (CT) scans for preoperatively detecting extrauterine-nodal disease and postoperative recurrent disease in patients with endometrial cancer.

Methods: We reviewed records of 702 women with primary endometrial carcinoma that was diagnosed between 1979 and 1993. Preoperative CT findings were compared with pathologic findings to assess nodal disease. The yield of postoperative CT was reviewed in clinically suspicious and routine settings.

Results: Among 492 women eligible for analysis, 178 (36%) had a total 326 CT scans. Among 56 women who had preoperative CT scans and lymph node samplings, positive and negative predictive values for nodal involvement were 50% and 94%, respectively, and sensitivity and specificity were 57% and 92%, respectively. Preoperative CT findings altered treatment plans in only six patients (8%). Forty-five asymptomatic women had 73 routine CT scans, and recurrence was diagnosed by CT in only two (4.4%). Thirty-seven women had CT scans for suspicion of recurrence, which was confirmed in 17 (46%). Kaplan-Meyer analysis showed no survival advantage in women with subclinical recurrences diagnosed by CT scan.

Conclusion: Routine preoperative CT scanning rarely alters treatment and is a poor predictor of nodal disease. Computed tomography in the postoperative period might be helpful for detection and follow-up of recurrent disease, but there was no difference in survival when subclinical recurrence was found by CT. Thus, CT scanning of any woman with endometrial cancer should be discouraged unless it is to evaluate symptoms.

Computed tomography (CT) has been proposed as a useful imaging tool for pretreatment staging and post-treatment evaluation of recurrence of gynecologic malignancies.^1–8 Some studies concluded that CT might accurately image large masses or extensive spread of disease, but that information might not translate into important alterations in treatment or improve survival.^9,10 Endometrial cancer is the most common gynecologic malignancy, with approximately 35,000 new cases annually. Preoperative CT is often done to evaluate the extent of myometrial invasion or to define extrauterine spread of disease, including lymphatic metastasis. Most women who present with stage I disease subsequently have surgical staging and treatment, so the value of preoperative radiographic staging seems limited. Postoperative indications for CT imaging vary. It can be used as a routine adjuvant to physical examination for detecting recurrence of disease in asymptomatic women or confirming clinical suspicions of recurrence that are not clearly evident on examination.

We reviewed records of patients with endometrial carcinoma during a 15-year period to determine whether CT imaging provided useful information to aid preoperative and postoperative treatment. We also evaluated whether diagnosis of subclinical recurrence of disease by CT compared with recurrences that were diagnosed clinically influenced survival.

	Materials and Methods

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Seven hundred two consecutive women with primary endometrial carcinoma diagnosed between 1979 and 1993 were identified by the cancer registry at The University of Iowa Hospitals and Clinics. This time frame was selected to encompass adequate follow-up and because CT imaging became available routinely in 1979. We reviewed charts and abstracted age, gravidity and parity, age at menopause, stage of disease, cell type, histologic grade, depth of invasion, nodal involvement, peritoneal cytology, current disease status, recurrence location, number of CT scans done, and indications for CT scanning. Patients were excluded from evaluation if their follow-up treatment was at another institution, if they had diagnosis of second malignancy, or if primary surgery was not planned initially. After exclusions, 492 women were available for analysis. Their disease was staged, depending on date of diagnosis, either by the 1971 International Federation of Gynecology and Obstetrics classification (FIGO) clinical staging criteria or the 1988 FIGO surgical classification. Node sampling in surgically staged cases was done according to the surgical guidelines of the Gynecologic Oncology Group’s surgical manual.

Computed tomographic scans were done with and without contrast at 1- and 2-cm intervals through the pelvis and abdomen. Pelvic and para-aortic lymph nodes were considered enlarged if they exceeded 1.5 cm.¹¹ Scans were coded as preoperative or postoperative. Indications for postoperative scans were classified as routine in asymptomatic patients, suspicious of recurrence in patients with symptoms but no clinically evident disease, or all other unrelated indications, including follow-up of previously abnormal scans. Use of CT imaging was based on treatment practices of individual gynecologic oncologists and no prospective algorithms were used to determine who was scanned preoperatively or postoperatively. Interpretations of preoperative CT were compared with histopathologic findings at laparotomy to determine sensitivity, specificity, and predictive value of CT evaluation of lymph node status. The utility of postoperative CT scans was reported in clinically suspicious and routine settings. Clinical and pathologic factors of women who were examined by postoperative CT scans were compared with those who did not have CT scans by Student t test for continuous variables and ² analysis for categorical variables. Survival analysis estimates were calculated by the Kaplan-Meyer method with the generalized Wilcoxon test. All statistical analyses were done using BMDP (BMDP, Los Angeles, CA) statistical software, with significance at P < .05.¹²

	Results

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The study spanned FIGO’s change from clinical to surgical staging for endometrial cancer. The distribution of study population across the staging systems is depicted in Table 1. Surgical staging increased the proportion of stage III disease from 5% to 16% primarily because of node sampling.

Women who had CT scans did not differ in age, gravidity, parity, or age at menopause compared with those not scanned (P > .05 for each factor). Postoperative CT scans were done more often in women with recurrent disease; 59 of 79 women (75%) with recurrence had CT scans whereas 20 (25%) were never scanned.

Among 75 women who had preoperative CT scans, treatment was modified based on CT findings in only six (8%). Three morbidly obese patients (body mass index 50, 59, and 61) had vaginal hysterectomies because no adenopathy or evidence of extrauterine disease was detected by CT. A fourth medically compromised patient had a vaginal hysterectomy after a negative preoperative scan. All those women were alive and without evidence of disease at the time of the analysis. Two women (3%) did not have surgery because CT detected advanced disease with large para-aortic adenopathy that was not anticipated at diagnosis. The first of those women was treated with primary chemotherapy and died of progressive disease 4 months after diagnosis. The second was treated with primary radiation therapy. She had residual disease in the uterus at the time of brachytherapy and was treated with progestin until she died of progressive disease 11 months later.

Fifty-six women had preoperative CT scans and lymph node sampling at laparotomy. Eight scans showed adenopathy suspicious of disease, and 48 scans showed no suspicious adenopathy. Three of 48 women with negative CT scans had lymph node metastases on pathologic evaluation. Four patients with CT-reported suspicious adenopathy had pathologically negative lymph nodes. Table 2 shows the correlation of preoperative CT and pathologic evaluation of lymph nodes. Sensitivity and specificity of preoperative CT for detecting nodal metastasis were 57% and 92%, respectively. Positive predictive value for nodal disease was only 50%; negative predictive value was 94%.

Thirty-seven women had a total of 41 scans to evaluate clinical symptoms of recurrence without clinically evident disease. Gastrointestinal complaints such as nausea, vomiting, or weight loss were the most commonly reported indications for scans in that group. Other indications included abdominal pain, increase in CA 125, unexplained jaundice, or lower-extremity deep venous thrombosis. Computed tomography provided evidence of recurrence in 17 patients (46%). All recurrences were confirmed by biopsy. Among 20 patients with clinical findings suspicious for recurrence not confirmed by CT, seven (35%) later had clinical diagnoses of recurrent disease.

One hundred thirty-seven CT scans were done in 61 women for indications other than suspicion of recurrence or routine surveillance. Those indications are listed in Table 3. Several patients were treated according to Gynecologic Oncology Group protocols and were required to have periodic CT evaluation by protocol. One woman had 16 CT scans while on that protocol, then had recurrence diagnosed by elevated CA 125 level between protocol-scheduled CT scans. Recurrence was confirmed by CT scan and she was subsequently observed using CA 125 levels. One woman (1.6%) in that group had an unexpected aortic node recurrence diagnosed by CT scan that was done as follow-up 6 months after a negative scan when she presented with a lower extremity deep venous thrombosis (the first scan was coded as not suspicious for recurrence).

View larger version (14K): [in this window] [in a new window]   Figure 1. Kaplan-Meyer survival curve for women with subclinical recurrent disease diagnosed by computed tomography scan (diamonds indicate median survival 42 months) and those recurrences clinically diagnosed (circles indicate median survival 32 months). Generalized Wilcoxon test shows no difference in survival P = .71.

	Discussion

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Previous reviews suggested that the usefulness of CT scanning is uncertain in preoperative treatment of endometrial cancer. Walsh and Goplerud⁷ concluded that there was "confirmed value" in preoperative CT scanning to evaluate women with advanced disease. They evaluated only 19 women and found that CT findings agreed with surgical staging in 16 of them, but two women had microscopic lymph node metastases that were not detected by CT scans. The sensitivity of 57% and positive predictive value of 50% for detecting nodal metastases in the present study suggest that preoperative CT is a poor predictor of nodal disease. The calculated sensitivity and positive predictive value are based on only seven cases with positive nodes (12.5%), so the values could be overestimates or underestimates. Although a specificity of 92% and negative predictive value of 94% (based on 49 cases with negative nodes) are reassuring for noninvolved nodes, CT scans should not be used in place of surgical sampling except in cases in which patients are believed to be at excessive risk for operative morbidity or mortality. Based on our results, we concluded that routine preoperative scanning in women who are to have surgical staging rarely alters the accepted treatment plan, is unreliable, and with rare exceptions (such as for medically compromised patients or those with marked obesity) should be discouraged.

A second issue is the utility of CT for detecting and helping treatment of recurrent disease. For CT scanning to be beneficial, it should be considered an accurate method of detecting tumor spread. However, as Franchi et al⁸ show, the major disadvantage of CT is the difficulty distinguishing inflammation and postsurgical or radiation therapy fibrosis from recurrent disease in the pelvis. Conversely, CT might provide supplementary data for deciding treatment options (surgery, chemotherapy, or radiation) for patients with known recurrent disease.

Our data indicated that routine use of CT scanning of asymptomatic women in the postoperative period to detect subclinical recurrence of disease was not effective. Only two of 45 asymptomatic women had recurrent disease diagnosed by CT, and both were expected to develop recurrent disease based on advanced stage at diagnosis. Both patients ultimately died of their disease, and their survival times were within the range of those for clinically diagnosed recurrences. The majority of CT-diagnosed recurrences were in women with clinical symptoms suggesting recurrence before scanning. In that setting, CT scanning detected subclinical recurrence in 46% of cases. When grouped together, the patients with CT-diagnosed recurrences lived no longer than those diagnosed clinically. As in Figure 1, the percentage of women alive at 5 years differs by less than 10% between the two groups. With only 20 cases of CT-diagnosed recurrences, the power of the Kaplan-Meyer analysis is limited. The data, as presented, can detect a 40–45% difference with 20% power; however, to detect the 10% difference seen in Figure 1 with the same 20% power would require more than 300 patients per group. Those limits notwithstanding, it appears that postoperative CT does not benefit patients in terms of survival.^12–14

	Footnotes

 
PII S0029-7844(99)00626-2

Received July 22, 1999. Received in revised form October 21, 1999. Accepted November 15, 1999.

	References

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11. Friedman AC, Radecki PD, Lev-Toaff AS, Hilport PL, eds. Clinical pelvic imaging. St Louis: The CV Mosby Company, 1990.

12. Kleinbaum DG, Kupper LL, Muller KE, eds. Applied regression analysis and other multivariable methods. 2nd ed. Boston: PWS-KENT Publishing Company, 1988.

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