The Effectiveness of Ovarian Cancer Screening

Transcription

1 The Effectiveness of Ovarian Cancer Screening A Decision Analysis Model Marilyn M. Schapira, MD, MPH; David B. Matchar, MD; and Mark J. Young, MD Objective: To estimate the effectiveness of ovarian cancer screening with CA 125 and transvaginal sonography. Design: Decision analysis was used to examine the no-screen compared with the screen strategy. Setting: Estimates of cancer incidence, survival, and life expectancy were derived from population-based data and clinical series. Subjects: A cohort of 40-year-old women of all races and residing in the United States. Interventions: A one-time screening intervention. The criterion standard for diagnosis of ovarian cancer was evaluation with exploratory laparotomy. Main Outcome Measure: Average years of life expectancy gained by women in the screened group. Results: Screening for ovarian cancer with a combination of CA 125 and transvaginal sonography increases the average life expectancy in the population by less than 1 day. Conclusions: Given the limited effect on overall life expectancy, it is unlikely that mass screening for ovarian cancer with CA 125 and transvaginal sonography would be an effective health policy. Annals of Internal Medicine. 1993;118: From the Medical College of Wisconsin, Milwaukee, Wisconsin; Duke University Medical Center, Durham, North Carolina; and Henry Ford Hospital, Detroit, Michigan. For current author addresses, see end of text. An important issue in the preventive health care of women is screening for gynecologic malignancies. The role of cervical cancer screening is well established, but an effective approach to ovarian cancer screening is still being sought. Ovarian cancer is the leading cause of death among gynecologic malignancies (not including breast cancer) and the fifth leading cause of all cancer deaths in women (1). In 75% of cases, the disease is detected in the late stage when 5-year survival is poor (1). Developing an effective screening test is an attractive strategy for improving survival. There are several problems, however, with an ovarian cancer screening approach. A low annual incidence, 13.8/ means that many people must be screened to find only a few cases of disease. In addition, an invasive procedure is needed to evaluate a positive screening test. This places a high financial, physical, and emotional cost on falsepositive screening tests. Given the complexity of the decision and the absence of a randomized, controlled trial to evaluate screening strategies for ovarian cancer, we turned to decision analysis to examine this issue. This allowed quantification of the effect of relevant factors and specification of test characteristics required for an effective screening strategy. The specific question we pose is, "will a onetime screen improve the average life expectancy in a cohort of 40-year-old women?" Natural History of Ovarian Cancer Incidence, Risk, and Prognostic Factors The annual incidence of ovarian cancer in the United States is 13.8/ with an annual incidence of death of 8.5/ (2). Its cause remains unknown, and survival rates have been relatively stable in the past 35 years (3). The strongest risk factor for the disease is increasing age. Other risk factors are family history of ovarian cancer, residence in a Western industrialized country, and nulliparity (4). Established protective factors are multiparity and oral contraceptive use (5). The most important prognostic factor for ovarian cancer is stage of disease at diagnosis (6). The present staging system for ovarian cancer was devised by the International Federation of Gynecology and Obstetrics. The system defines stage I as disease limited to the ovaries, stage II as disease limited to the true pelvis, stage III as disease that involves intraperitoneal spread, and stage IV as disease with distant metastasis. Other independently prognostic factors are the size of residual tumor remaining after a surgical debulking procedure and the histologic grade of the tumor (6). Clinical Presentation and Disease Course Ovarian cancer is often silent in the early stages of disease, yet aggressive and resistant to treatment late in its course when most cases become clinically apparent. Ovarian cancer first spreads locally with metastasis to the contralateral ovary, the uterus, and the fallopian tubes. Further dissemination occurs through the peritoneum to involve the omentum, bowel, and retroperitoneal lymph nodes. Hematogenous spread is rare but can result in distant metastasis. As the disease progresses, gastrointestinal and urinary tract obstruction are common. These late complications are often resistant to effective medical or surgical intervention because of the extensive amount of disease. Most deaths occur within 5 years of diagnosis (7). Early diagnosis of ovarian cancer is difficult because symptoms are often vague and nonspecific. Presenting symptoms include abdominal swelling and pain, abnor American College of Physicians

2 mal uterine bleeding, and gastrointestinal and urinary complaints (8). A retrospective study of 277 patients with primary ovarian cancer reports the average patient delay in seeking medical evaluation after the onset of symptoms to be 9.1 months and the average physician delay in performing pelvic examination in symptomatic patients to be 9.6 months (9). The clinical significance of these delays is not known. Available Screening Tests The optimal characteristics of a screening test include ease of performance, patient acceptability, limited expense, lack of complications, and high sensitivity and specificity. Sensitivity is defined as the proportion of patients with the target disorder who have a positive test result. Specificity is defined as the proportion of patients without the target disorder who have a negative test result (10). Screening tests that have been proposed for ovarian carcinoma include manual pelvic examination, cytologic detection, serologic testing with monoclonal antibodies, abdominal ultrasound, and transvaginal sonography (TVS). Of these, the monoclonal antibody to the CA 125 antigen and TVS are the most promising because of their high specificity and reproducibility and ease of performance. The test characteristics of these modalities are described below. Pelvic Examination and Cytologic Detection No evidence exists that annual pelvic examinations for detecting cervical cancer in asymptomatic women have increased case finding for early ovarian cancer. Compared with abdominal ultrasonography, the pelvic examination reportedly detects 34% of adnexal masses and over-reads 8% (11). The cervical Papanicolaou smear, which is an effective test for the early detection of cervical cancer, is not a good screening test for ovarian carcinoma. In a population of 164 patients diagnosed with ovarian carcinoma, only 11% had a positive Papanicolaou smear (12). Peritoneal and cul-de-sac lavage have also been investigated as possible screening tests for ovarian cancer but are cumbersome to perform and have poor test performance (13, 14). Abdominal Ultrasonography Abdominal ultrasonography has been evaluated extensively as a screening test for ovarian cancer. Uncontrolled screening trials have provided information on test characteristics but have failed to show a convincing benefit in terms of the detection of early-stage disease. The specificity of abdominal ultrasound scans in the detection of ovarian cancer was estimated to be 97.7% (95% CI, 96.4% to 99.0%) in a study of 5000 asymptomatic women aged 18 to 78 years (mean age, 52 years) who were screened with abdominal ultrasound for 3 consecutive years (15). The sensitivity of abdominal ultrasound scan to detect a pelvic mass was found to be 90% in a study of 72 women with a diagnosis of pelvic mass who subsequently had laparotomy (16). Abdominal ultrasonography has the disadvantages of being time consuming and expensive and requiring significant patient preparation. Transvaginal Sonography The use of TVS has been proposed as an alternative to abdominal ultrasound in ovarian cancer screening. Transvaginal sonography was developed to improve the resolution of abdominal ultrasound and provides detailed imaging of the ovary and masses confined to the true pelvis. It is easy to perform, well accepted by patients, and shows strong interobserver interpreter agreement (17, 18). In premenopausal women, a normal ovary is defined as having a volume of 18 cm 3 or less and being uniformly hypogenic or entirely cystic. If the ovary is enlarged but the structure is normal, the scan is repeated 1 week after menses. If the scan remains abnormal, the test is considered positive. In postmenopausal women, a normal ovary is defined as having a volume of 8 cm 3 or less and a uniformly hypogenic internal structure. Any ovary that exceeds this volume or shows complex or solid areas on sonography is defined as abnormal. The specificity of TVS for ovarian carcinoma was found to be 98.1% (CI, 97.4% to 98.8%) in a study of 1300 asymptomatic postmenopausal women who underwent screening with TVS (17). The sensitivity of TVS in the detection of an ovarian mass was found to be 90% in a study of postmenopausal women undergoing elective surgery for reasons unrelated to adnexal disease (19). Transvaginal sonography with color flow imaging is under investigation as a screening modality (20). This test can detect intraovarian vascular changes and measure impedance to blood flow in ovarian masses as potential indices of early malignancy. This technique may increase the specificity of conventional ultrasound examinations. Monoclonal Antibodies The development of monoclonal antibodies reactive to tumor-specific antigens has been applied to the diagnosis and management of ovarian cancer. The most promising monoclonal antibody with respect to ovarian cancer screening is 0C 125, which reacts to the CA 125 antigen. It was originally reported that serum CA 125 was greater than 35 U/mL in 83% of patients with epithelial ovarian cancer and 1% of presumably healthy blood donors (21). CA 125 was also found to be elevated in nongynecologic carcinomas and benign abdominal disorders such as pancreatic pseudocyst, uterine fibroids, and endometriosis (21). The sensitivity of CA 125 for ovarian cancer increases with the clinical stage at diagnosis, 50% for stage I and II neoplasms and 90% for stage III and IV neoplasms (22, 23). The specificity of CA 125 for ovarian cancer was determined to be 97.6% in a prospective study of 5550 women ages 40 years or older who were screened with CA 125. In the study, an elevated level of CA 125 was followed with physical examination, abdominal ultrasound, and serial CA 125 levels, with further management based on clinical and sonographic findings (24). 1 June 1993 Annals of Internal Medicine Volume 118 Number

3 Figure 1. Ovarian cancer decision tree. The decision tree is designed to test the strategy of no-screen compared with a one-time screen for a population of healthy 40- year-old women. There are two options at the decision node: noscreen or screen. A series of chance nodes represent the following points of uncertainty: the likelihood of disease, the percentage of prevalent disease in the early stage at the time of the screen, the clinical detection rate of early disease, the detection rate of early disease with the screening strategy, the specificity of the screening test, and the mortality rate associated with diagnostic laparotomy. Assigned to each terminal node is the life expectancy for an individual whose experience corresponds to that path in the decision tree. These include the life expectancy of a 40-year-old woman with no disease, with earlystage disease, and with late-stage disease. For health states that require a laparotomy, 1 week is subtracted from life expectancy. For health states in which disease had progressed from early- to late-stage before diagnosis, 1 year is added to life expectancy. Methods The Decision Analysis Model We designed a decision tree to test the strategy of a onetime screen versus no screen for a population of healthy 40- year-old women (Figure 1). We modeled the use of CA 125 and TVS as individual and combined screening tests. When used in combination, an abnormal test was required of both modalities to define a positive screen. A decision tree is a diagram that describes a clinical decision and possible outcomes of that decision. The tree begins with a decision node that represents an active choice that is to be made by the patient or physician. Each point of uncertainty is represented by a chance node. Branches of chance nodes indicate possible health states. Each health state is associated with a probability. Each branch ends in a terminal node, or final outcome, representing the average life expectancy of that health state. The estimated value of a strategy is determined by weighting the value of the final outcomes by the probability of its occurrence. To examine uncertainty in the model, each probability is examined independently for a range of plausible values. In this model, there are two options at the decision node: no-screen or screen. A series of chance nodes represent the following points of uncertainty: the likelihood of disease, the percentage of disease that is in the early stage at the time of the screening test, the clinical detection of early disease, the detection of early disease with a screening strategy, the specificity of the screening test, and the mortality rate associated with diagnostic laparotomy. Assigned to each terminal node is the life expectancy for an individual whose experience corresponds to that path in the decision tree. These include the life expectancy of a 40-year-old woman with no disease, with early-stage disease, and with late-stage disease. Assumptions Several assumptions are made in the model to simplify the analysis yet retain the basic clinical issues. First, we assume that survival time for early disease detected clinically is the same as survival time for early disease detected by screening, effectively correcting for potential lead-time bias (25). Second, we assume that the morbidity and mortality rates associated with a diagnostic laparotomy are the same for patients with and without disease. Third, we disregard the potential benefit of identifying benign disease. Finally, we model only a onetime screen. Probabilities The baseline values and range of plausible values used in the decision tree are summarized in Table 1. The prevalence of June 1993 Annals of Internal Medicine Volume 118 Number 11

4 Table 1. Baseline Estimates and Range of Plausible Values Used in the Decision Tree* Variable Interpretation Baseline Value Range for Sensitivity Analysis pi Disease prevalence 28.6/ p2 Percentage of prevalent cases in early-stage disease 50% p3 Percentage of early-stage disease diagnosed clinically without a screening program 25% p*t oensiiivny oi w\ IZJ ana l Voy as comoinea tests ror early-stage disease 45% pj oensiiiviiy oi w\ IZJ ana ivo as comoinea tests ior late-stage disease 81% p6 Specificity of CA 125 and TVS as combined tests 99.95% p7 Probability of postlaparotomy death 0.23% * The notations pi through p7 correspond to the probabilities associated with each outcome in the decision tree. t TVS = transvaginal sonography. 20 to 200/ % to 80% 20% to 80% 20% to 80% 50% to 100% 96% to 100% 0.0% to 10.0% undiagnosed disease can be calculated by the equation m = P/I, where m is the average duration of the preclinical phase of disease and I is the incidence of disease (26). Based on an incident rate of 14.3/ and assuming a preclinical disease phase of 2 years, we estimate the prevalence of ovarian cancer in women aged 40 years to be 28.6/ (2). The range of values considered varied from 20 to 200/ There are no direct data on the distribution of early- compared with late-stage disease in the population. It was estimated that 50% of prevalent cases at any given time are in the early stage of disease. The range of values considered varied from 20% to 80%. The percent of prevalent early-stage cases detected by current clinical practice is not known. Approximately 24% of incident ovarian cancers are diagnosed at an early stage (1). Thus, it was estimated that without a screening intervention, 25% of disease in the early stage will be diagnosed clinically before progressing to late-stage disease. The range of values considered varied from 20% to 80%. The sensitivity and specificity of the combined approach can be calculated from the test characteristics of the individual tests assuming conditional independence of the test modalities. This assumption is reasonable because the tests are based on different aspects of the tumor, one measuring the antigen released by tumor cells and one measuring the anatomic features of the tumor. The estimate of sensitivity for the combined strategy is 45% for early disease and 81% for late disease. We considered a plausible range of values from 20% to 80% for early disease and 50% to 100% for late disease. The estimate of specificity for the combined strategy is 99.95%; it varied from 96% to 100%. Mortality rate for a diagnostic exploratory laparotomy, taken from the National Halothane Study, was estimated to be 0.23% (27). The estimate is consistent with postoperative mortality rates in studies of elective staging procedures for Hodgkin disease (28). For sensitivity analysis, this estimate varied from 0.0% to 10.0%. Measure of Benefit Benefit is quantified as improvement in life expectancy. Life expectancy is estimated using the Declining Exponential Approximation of Life Expectancy method (29). The average life expectancy of a 40-year-old woman in the United States is 40.2 years (30). The life expectancies of those with early-stage and late-stage ovarian cancer are estimated to be years and 2.95 years, respectively. These calculations are based on studies reporting a 5-year survival rate of 81% for early-stage disease (median age of study population, 58 years) and a mean survival of 1.98 years for late-stage disease (median age of study population, 54 years) (31, 32). For patients whose early disease progressed to late disease before diagnosis, 1 year is added to life expectancy to account for the time taken to progress from early- to late-stage disease. To account for the discomfort and inconvenience of laparotomy, 1 week is subtracted from the life expectancy of those patients undergoing surgery in the baseline case. Analysis The average life expectancy of the no-screen option compared with the screen option was calculated. A test strategy combining CA 125 and TVS was used as the baseline case. Sensitivity analysis was performed by independently changing the estimates of the following variables: disease prevalence, distribution of early- and late-stage disease, detection rate of early disease in usual clinical practice (the no-screen strategy), mortality rate for diagnostic exploratory laparotomy, transition time from early- to late-stage disease, and the sensitivity and specificity of the screening test. When the preferred strategy changed over the plausible range on any variable, a threshold value was calculated; above the threshold value one strategy was preferred; below the threshold value, the other strategy was preferred. Results Baseline and Sensitivity Analysis When CA 125 and TVS were used in combination, the expected value of the screen option was greater than the expected value of the no-screen option ( years compared with years). The screen strategy increased the average life expectancy by approximately one third of a day of life. Sensitivity analysis was done to determine threshold values for the baseline screening strategy. The no-screen strategy was favored if the postoperative mortality rate exceeded 7.32% or the specificity of the test was less than 98.53% (Table 2). Screening in the Elderly The prevalence of ovarian cancer increases with age (33). To assess the effectiveness of screening in the elderly, we applied the model to a population of 65- Table 2. Threshold Values for the Use of CA 125 and Transvaginal Sonography as Combined Tests* Variabl le P6 P7 Interpretation Specificity of screening test Probability of postlaparotomy death Range of Values, % 96 to 100 Threshold Value, % to * When the preferred strategy changes over a plausible range of values, a threshold value is calculated. The notations p6 and p7 correspond to probabilities in the decision tree. 1 June 1993 Annals of Internal Medicine Volume 118 Number

5 Table 3. Estimates and Threshold Analysis for Cohort of 65-Year-Old Women* Variable Interpretation Baseline Value Range for Sensitivity Analysis Threshold Value pi Disease prevalence 93.8/ to 300/ p6 Specificity of combined tests 99.95% 96% to 100% 99.25% p7 Mortality rate of diagnostic laparotomy 1.50% 0.0% to 10.0% * The notations pi, p6, and p7 correspond to the probabilities in the decision tree. Estimates not included in this figure are identical to those of the younger cohort in Table 1. year-old women. The life expectancy of a healthy 65- year-old is years (2). Estimates of life expectancy for 65-year-old women with early- and late-stage ovarian cancer are years and 2.72 years, respectively (30, 31). The baseline variable estimates and range of plausible values for prevalence and postoperative death are given in Table 3 (2, 27). The model favored the screen strategy in the elderly cohort as with the younger cohort, but only by a small amount. Average life expectancy in the screened population was increased by approximately three quarters of a day of life ( years compared with years). Sensitivity analysis found a threshold value for test specificity of 99.25%, below which the no-screen strategy would be favored. Discussion Although effective treatment for ovarian cancer is available, the disease is usually detected too late for women to gain the full benefit of treatment. Early detection remains the best hope for reducing the casemortality rate. Some gains in early detection may be possible from prompt attention of patients and physicians to early signs and symptoms of the disease. But undoubtedly many cases will be asymptomatic until the disease has spread beyond the local stage. Thus, the role of screening is an essential question in the clinical approach to ovarian cancer. The best tests available for ovarian cancer screening are CA 125 and TVS. However, their use is considered experimental because a decrease in the case-mortality rate from screening has not been demonstrated (34). We used a decision analysis model to evaluate the effect of ovarian cancer screening on life expectancy. We chose to model a test strategy combining CA 125 and TVS to optimize test specificity. A high rate of test specificity is essential in designing a screening strategy for a disease with low prevalence. However, despite an estimated specificity of 99.95%, the benefit in terms of life expectancy was very small. The morbidity and mortality rates associated with ovarian cancer screening might be decreased if an alternative to laparotomy was available to serve as a criterion standard for diagnosis. Laparoscopy, the insertion of a fiber-optic instrument in the peritoneum, might have a role in situations when the clinical work-up is suggestive of a benign mass. However, it is not always possible to distinguish a benign cyst from malignant disease before the tissue is examined histologically (35). Because of concern that manipulation and spillage of an unexpectantly malignant tumor might occur, laparoscopy has no defined role in the diagnosis of ovarian cancer at this time (36). Ultimately, the problem with screening for ovarian cancer is the low prevalence of disease. It is difficult to design effective screening strategies for rare conditions (37). The prevalence of ovarian cancer is lower than that of other malignant diseases we screen for such as breast, colon, and prostate cancer. Future screening or case-finding strategies might focus on identifying a population with a higher prevalence of disease. This population would include those with multiple risk factors such as family history and nulliparity, not only age alone. Although prevalence increases with age, the increased mortality rate associated with laparotomy and the decreased life expectancy in the elderly limits the effectiveness of a screening strategy in this age group. Mass screening for ovarian cancer will not improve average life expectancy in the population by a meaningful amount of time and cannot be recommended as an effective health policy. Primary care physicians must continue to be clinically astute in evaluating patients who have signs and symptoms suggesting ovarian cancer, such as abnormal vaginal bleeding or undiagnosed abdominal discomfort. Researchers have an ongoing challenge to identify characteristics that predict a population with a sufficiently high prevalence to make available tests useful for detection of preclinical disease. Acknowledgments: The authors thank John Pauk, MD, MPH, for review of the manuscript. Requests for Reprints: Marilyn M. Schapira, MD, Section of General Internal Medicine, 5000 W. National Avenue, Clement J. Zablocki Veterans Affairs Medical Center, 111-B, Milwaukee, WI Current Author Addresses: Dr. Schapira: Section of General Internal Medicine, 5000 W. National Avenue, Clement J. Zablocki Veterans Affairs Medical Center, III-B, Milwaukee, WI Dr. Matchar: Duke University/Center for Health Policy Research and Education, 125 Old Chemistry Building, Durham, NC Dr. Young: Department of Internal Medicine, Henry Ford Hospital, 2799 W. Grand Boulevard, Detroit, MI References 1. American Cancer Society. Cancer statistics, CA Cancer J Clin. 1990;40: Cutler SJ, Young JL; eds. Third National Cancer Survey: Incidence Data, National Cancer Institute Monograph no. 41, DHEW publication (NIH) Washington, DC: U.S. Government Printing Office; Heintz AP, Hacker NF, Lagasse LD. Epidemiology and etiology of ovarian cancer: a review. Obstet Gynecol. 1985;66: Parazzini F, Franceschi S, La Vecchia C, Fasoli M. The epidemiology of ovarian cancer. Gynecol Oncol. 1991;43: Slotman BJ, Rao BR. Ovarian Cancer (review). Anticancer Res. 1988;8: Sigurdsson K, Aim P, Gullberg B. Prognostic factors in malignant epithelial ovarian tumors. Gynecol. Oncol. 1983;15: Kent SW, McKay DG. Primary cancer of the ovary: an analysis of 349 cases. Am J Obst Gynecol. 1960;80: June 1993 Annals of Internal Medicine Volume 118 Number 11

6 8. Pearse WH, Behrman SJ. Carcinoma of the ovary. Obstet Gynecol. 1954;3: Sackett DL, Haynes RB, Tugwell P. Clinical Epidemiology. Boston: Little, Brown and Company; Andolf E, Svalenius E, Astedt B. Ultasonography for early detection of ovarian carcinoma. Br J Obstet Gynaecol. 1986;93: Parker RT, Parker CH, Wilbanks GD. Cancer of the ovary. Am J Obstet Gynecol. 1970;108: Keettel WC, Pixley EE, Buchsbaum HJ. Experience with peritoneal cytology in the management of gynecologic malignancies. Am J Obstet Gynecol. 1974;120: Funkhouser JW, Hunter KK, Thompson NJ. The diagnostic value of cul-de-sac aspiration in the detection of ovarian carcinoma. Acta Cytol. 1975;19: Campbell S, Bhan V, Royston P, Whitehead MI, Collins WP. Transabdominal ultrasound screening for early ovarian cancer. BMJ. 1989;299: Reeves RD, Drake TS, O'Brien WF. Ultrasonographic versus clinical evaluation of a pelvic mass. Obstet Gynecol. 1980;5: Van Nagell JR Jr, DePriest PD, Puis LE, Donaldson ES, Gallion HH, Pavlick EJ, et al. Ovarian cancer screening in asymptomatic postmenopausal women by transvaginal sonography. Cancer. 1991;68: Higgens RV, van Nagell JR Jr, Donaldson ES, Gallion HH, Pavlick, Endicott B, et al. Transvaginal sonography as a screening method for ovarian cancer. Gynecol Oncol. 1989;34: Rodriguez MH, Piatt LD, Medearis AL, Lacarra M, Lobo RA. The use of transvaginal sonography for evaluation of postmenopausal ovarian size and morphology. Am J Obstet Gynecol. 1988; 159: Bourne T, Campbell S, Steer C, Whitehead MI, Collins WP. Transvaginal color flow imaging: a possible new screening technique for ovarian cancer. BMJ. 1989;299: Bast RC Jr, Klug TL, St John E, Jenison E, Niloff JM, Lazarus H, et al. A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer. N Engl J Med. 1983;309: Zurawski VR Jr, Knapp RC, Einhorn N, Kenemans P, Mortal R, Onmi K, et al. An initial analysis of preoperative serum CA 125 levels in patients with early stage ovarian carcinoma. Gynecol Oncol. 1988;30: Jacobs I, Bast RC Jr. The CA 125 tumour-associated antigen: a review of the literature. Hum Reprod. 1989;4: Einhorn N, Sjovall K, Knapp RC, Hall P, Scully RE, Bast RC Jr, et al. Prospective evaluation of serum CA 125 levels for early detection of ovarian cancer. Obstet Gynecol. 1992;80: Podell RN. Estimating the number of unnecessary deaths from breast cancer. J Chronic Dis. 1969;22: Prorok PC, Connor RJ, Baker SG. Statistical considerations in cancer screening programs. Urol Clin North Am. 1990;17: Summary of the National Halothane Study. Possible association between halothane anesthesia and postoperative hepatic necrosis. JAMA. 1966;197: Wobbes T, Lubbers EJ, de Pauw BE. Results and complications of staging laparotomy in Hodgkin's disease. J Surg Oncol. 1984;26: Beck RJ, Pauker SG, Gottlieb JE, Klein K, Kassirer JP. A convenient approximation of life expectancy (The "DEALE"): II. Use in medical decision-making. Am J Med. 1982;73: Vital statistics of the United States, Hyattsville, Maryland. United States Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Center for Health Statistics; Bjorkholm E, Pettersson F, Einhorn N, Krebs I, Nilsson B, Tjernberg B. Long-term follow-up and prognostic factors in ovarian carcinoma: The radiumhemmet series 1958 to Acta Radiol [Oncol]. 1982;21: Neigit JP, van der Berg ME, van Oosterom AT, Vriesendorp R, Kooyman CD, et al. Randomized trial comparing two combination chemotherapy regimens (HEXA-CAF vs CHAP-5) in advanced ovarian carcinoma. Lancet. 1984;2: Yancik R, Ries LG, Yates JW. Ovarian cancer in the elderly: An analysis of Surveillance, Epidemiology, and End Results program data. Am J Obstet Gynecol. 1986;154: van Nagell JR Jr, DePriest PD, Gallion HH, Pavlik EJ. Ovarian cancer screening. Cancer 1993;71: Maiman M, Seltzer V, Boyce J. Laparoscopic excision of ovarian neoplasms subsequently found to be malignant. Obstet Gynecol. 1991;77: Schwartz PE. An oncologic view of when to do endoscopic surgery. Clin Obstet Gynecol. 1991;34: Report of the U.S. Preventative Services Task Force. Guide to clinical preventive services. Maryland: Williams & Wilkins; 1990: xxix-xxiii. 1 June 1993 Annals of Internal Medicine Volume 118 Number