GYNECOLOGIC ONCOLOGY 46, 275-280 (1992)

Clinical Surveillance of Gynecologic Cancer Patients’ DANNY BARNHILL, M.D.,*,* DENNIS O’CONNOR, M.D.,* JOHN FARLEY, M.D.,* MICHAEL TENERIELLO, M.D.,*

DAVID ARMSTRONG, PH.D.-I- AND ROBERT PARK, M.D.*

*Gynecologic Oncology Service, Department of Obstetrics and Gynecology, Walter Reed Army Medical Center, Washington, D.C. 20307; and TDepartment of Clinical Investigation, Bethesda Naval Hospital, Bethesda, Maryland 20814

Received March 27, 1992

A survey of gynecologic oncologists was used to determine the optimum follow-up plan for asymptomatic, disease-free patients previously treated for a gynecologic malignancy. Ninety-four (91%) of 103 questionnaires were completed and returned. The majority of respondents recommended a clinic visit for these pa- tients every 3 months for the first year after the completion of therapy, every 3 or 4 months for the second year, every 6 months for the following 3 years, and then annually after this initial S- year period. Breast, abdominal, lymph node, and pelvic exam- inations, as well as a pap smear and stool guaiac, were done at each of these clinic visits. A yearly chest X ray was performed by the majority of the survey respondents for the first 3 years following initial treatment. Determinations of serum CA-125 and ovarian germ cell tumor markers were done at each follow-up appointment during the tirst 5 years after therapy if they were previously elevated. The patients’ smoking habits were discussed with them by the majority of respondents. Mammograms were performed periodically before age 50 and then yearly after age 50 by most respondents. Serum cholesterol determinations were accomplished every 5 years or more frequently if indicated. Cal- cium supplementation was recommended for postmenopausal pa- tients. The majority of respondents did not recommend routine vitamin supplementation or surveillance sigmoidoscopy. o 1~~2 Academic Pre.w, Inc.

INTRODUCTION

The frequency of follow-up office visits for previously treated gynecologic cancer patients has not been estab- lished. The extent of the physical evaluation and the fre- quency of surveillance studies, including X-ray procedures and serum tumor markers, have also not been deter-

’ The opinions and assertions contained herein are those of the au- thors and are not to be construed as official or as representing the views of the Department of the Army, the Department of the Navy, or the Department of Defense.

* To whom correspondence and reprint requests should be addressed at present address: Department of Obstetrics and Gynecology, Loui- siana State University Medical Center, 1501 Kings Highway, Shreveport, LA 71130.

mined. While those patients with medical complications, unexplained symptoms, or evidence of recurrent tumor should undergo intense follow-up and evaluation, moni- toring guidelines have not been set for healthy, asymp- tomatic women who are potentially cured and who con- tinue to be clinically free of disease.

Through a survey of gynecologic oncologists, this report seeks to determine the most appropriate follow-up plan for patients previously treated for a gynecologic malig- nancy who are asymptomatic and clinically disease-free. In addition to determining the best surveillance plan for recurrent gynecologic cancer, the responsibility of the gy- necologic oncologist to address other health issues, as measured by the current practice standards of the study group, is also evaluated.

MATERIALS AND METHODS

A questionnaire was mailed to 103 gynecologic oncol- ogists who were identified in the 1990 membership di- rectory of the Society of Gynecologic Oncologists (SGO) as full members having a primary academic affiliation. The study group had belonged to the SGO for an average of 10 years. Practice profiles were solicited from these individuals because of their proven clinical experience and their influence on the practice habits of fellows and res- idents. The survey consisted of 15 questions concerning the outpatient visits of women after the completion of therapy for a gynecologic malignancy. These questions concerned only the follow-up of potentially cured, asymp- tomatic patients with no clinical evidence of recurrent tumor. All responses were anonymous. Statistical signif- icance analysis was performed using Fisher’s exact test.

RESULTS

Of the 103 questionnaires mailed, 94 (91%) were com- pleted and returned. The following responses were obtained:

275 0090-8258/92 $4.00

Copyright 0 1992 by Academic Press, Inc. All rights of reproduction in any form reserved.

276 BARNHILL ET AL.

TABLE 1 The Recommended Interval for Clinic Visits after the

Completion of Treatment for a Gynecologic Malignancy

Year after therapy

1 2 3 4 5 >5

Recommended interval Number of survey respondents

Monthly 5 0 0 0 0 0 Every 2 months 24 4 0 0 0 0 Every 3 months 65 47 7 2 1 0 Every 4 months 0 41 28 9 3 0 Every 5 months 0 0 1 3 0 0 Every 6 months 0 2 57 76 80 31 Every 12 months 0 0 1 4 10 63

How frequently do you recommend the asymptomatic patient with no clinical evidence of disease be seen in your clinic for routine follow-up after completing therapy for an invasive gynecologic malignancy? Table 1 shows the distribution of recommended clinic visits. For the majority of survey respondents, the first year follow-up interval after completion of therapy is 3 months. It is every 3 or 4 months for the second year. For the third, fourth, and fifth years the follow-up interval is 6 months. After the fifth year, the majority recommend yearly office visits.

What examinations are done at each of those visits to your clinic? All 94 respondents perform a pelvic exami- nation at each follow-up visit. Ninety-three (99%) per- form an abdominal examination, 91 (97%) do a lymph node examination, and 65 (69%) conduct a breast ex- amination at each visit. Seventy-nine (84%) do a pap smear, and 48 (51%) check a stool guaiac with every rectovaginal examination.

Zf a breast, abdominal, lymphatic, and pelvic exami- nation and pap smear or stool guaiac are not done at every examination, how frequently do you do them? This ques- tion was not answered frequently enough to generate meaningful results.

TABLE 2 Surveillance X-ray Studies Recommended after the Completion

of Treatment for a Gynecologic Malignancy

Year after therapy

1 2 3 4 5 >5

Recommended study Number of respondents

Chest X ray 68 66 50 45 46 2 Intravenous pyelogram 22 12 3 1 4 0 CAT scan 35 27 14 9 8 0 Barium enema 1 1 1 1 1 0

TABLE 3 Surveillance Serum CA-125 Levels Recommended after the

Completion of Treatment for an Epithelial Ovarian Carcinoma

Year after therapy

1 2 3 4 5 >5

Number of determinations recommended each year Number of survey respondents

0 10 10 12 15 17 34 1 1 1 2 2 9 31 2 1 5 34 56 56 27 3 3 18 21 11 3 0 4 42 46 19 8 7 2 5 1 1 0 0 0 0 6 25 11 5 1 1 0 8 1 0 0 0 0 0 9 2 0 0 0 0 0

12 8 2 1 1 1 0

What categories of health care providers perform the follow-up clinical evaluation of your patients? In 91(97%) of the 94 practices represented by the survey respondents, gynecologic oncologists participate in the surveillance of these follow-up patients. Nonsubspecialty trained obste- trician-gynecologists participate in 15 (16%) of the office practices, Gynecologic Oncology fellows in 29 (31%), Ob- stetrics and Gynecology residents in 69 (73%), interns in 5 (5%), medical students in 9 (lo%), physicians’ assistants in 2 (2%), and clinical nurse specialists participate in 2 (2%) of the follow-up clinics of the respondents.

In the average disease-free asymptomatic patient who has completed treatment for a gynecologic malignancy, and who is not participating in a research protocol which re- quires specific surveillance studies, how often do you order a chest X ray, intravenous pyelogram, barium enema, or CT scan? The recommendation for surveillance X-ray studies varies widely among the respondents. Table 2 shows which studies are ordered routinely. The majority of the 94 respondents obtain a yearly chest X ray for the first 3 years after completion of therapy.

In the average asymptomatic ovarian epithelial carci- noma patient who is clinically free of disease, how often, if ever, do you perform surveillance CA-125 levels after completion of therapy? Assume the CA-125 was elevated prior to instituting primary treatment. For patients in whom the CA-125 was elevated prior to beginning ther- apy, the recommended number of times it should be checked covers a broad range (Table 3). The median recommendation is four times each year during the first 2 years following completion of treatment, then twice each year for the next 3 years. The respondents are almost equally divided between obtaining a CA-125 level zero, one, or two times each year after the initial 5-year period.

CLINICAL SURVEILLANCE OF GYNECOLOGIC CANCER PATIENTS 277

TABLE 4 Surveillance Tumor Marker Levels Recommended after the

Completion of Treatment for an Ovarian Germ Cell Tumor

Year after therapy

1 2 3 4 5 >5

Number of determinations recommended each year Number of survey respondents

0 8 9 14 20 23 44 1 1 3 3 8 12 29 2 2 4 35 54 53 21 3 2 19 24 7 2 0 4 43 46 14 3 3 0 6 24 11 4 2 1 0 8 1 0 0 0 0 0 9 1 1 0 0 0 0

12 12 1 0 0 0 0

Between 11 and 18% of respondents do not recommend routine CA-125 testing during the 5 years after completion of therapy.

In the average asymptomatic ovarian germ cell tumor patient who is clinically free of disease, how often, if ever, do you perform surveillance levels of specific tumor mark- ers after completion of therapy if those markers were el- evated prior to treatment? For patients with an ovarian germ cell tumor with a previously elevated serum marker, the range of recommended determinations also varies widely (Table 4). The median recommendation is four times each year during the first 2 years following com- pletion of treatment and then twice each year for the next 3 years. There is no clear consensus recommendation after the initial 5-year period. Between 8 and 23% of respond- ents do not recommend routine germ cell tumor marker testing during the 5 years after completion of therapy.

For the average patient who receives follow-up exami- nations in your gynecologic oncology clinic, is that the only source of gynecologic care those women receive? Sixty-one (65%) of the respondents are the only source of gynecologic care that their patients receive. Twenty- nine (31%) respondents are not the only source of gy- necologic care, 3 (3%) are uncertain, and 1 (1%) gave no answer.

How often do you order a serum cholesterol level for your patients who have completed therapy for a gyneco- logic malignancy and are disease-free? Thirty-five (37%) of the respondents never order a serum cholesterol de- termination for their patients. Thirty (32%) order a level every 5 years, 28 (30%) check the cholesterol on a tailored schedule, and 1 (1%) gave no response.

Do you prescribe or recommend oral vitamin supple- mentation to your routine follow-up gynecologic oncology

patients? Sixty-five (69%) of the respondents do not rou- tinely recommend vitamin supplementation to their pa- tients. Twenty-four (26%) prescribe a daily vitamin, 4 (4%) prescribe vitamins on a tailored regimen, and 1 (1%) did not respond.

Do you prescribe or recommend oral calcium supple- mentation to your average routine follow-up gynecologic oncology patients who are naturally or surgically meno- pausal? Of the 56 (60%) respondents who prescribe daily calcium supplementation to their postmenopausal pa- tients, 6 (6%) recommend 500 mg of elemental calcium, 27 (29%) recommend 1000 mg, 21 (22%) recommend 1500 mg, and 2 (2%) recommend a tailored regimen. Thirty-seven (39%) of the respondents do not prescribe calcium supplementation for their postmenopausal pa- tients, and 1 (1%) gave no answer.

Do you or your medical team members ask your routine follow-up gynecologic oncology patients at each visit if they smoke? Twenty-five (27%) of the respondents do not ask their patients if they smoke. Twenty-seven (29%) make it a routine to ask at each visit, and 41 (44%) do not ask at each visit but do have this information clearly noted in the outpatient record. One (1%) respondent gave no answer.

In the average disease-free, asymptomatic patient who has completed treatment for a gynecologic malignancy and who has no family history of breast cancer, how often do you order a mammogram? Seventy-six (81%) of the re- spondents order periodic screening mammograms for their patients before age 50 and then yearly after age 50. Nine (10%) order regular mammograms on a tailored regimen. Six (6%) obtain a yearly mammogram on all of their patients regardless of age. Two (2%) never order a mammogram, and 1 (1%) did not respond to this question.

In the disease-free asymptomatic patient who has com- pleted treatment for a gynecologic malignancy and who has no family history of colon cancer, how often do you order sigmoidoscopy? Forty-seven (50%) of the survey respondents never order surveillance sigmoidoscopy for their patients. Twenty-six (28%) order regular sigmoi- doscopy on a tailored schedule. Twenty (21%) order sig- moidoscopy yearly at age 50 until negative for two con- secutive years and then every 3 to 5 years. One (1%) respondent did not answer this question.

Do you believe it should be the responsibility of the gynecologic oncologist to monitor the disease-free, asymp- tomatic follow-up gynecologic cancer patient for vitamin use, serum cholesterol level, calcium use, smoking cessa- tion, breast cancer screening, or colon cancer surveillance? Eighty-six (91%) respondents believe it is the responsi- bility of gynecologic oncologists to arrange breast cancer screening for their patients. Sixty-five (69%) believe gy- necologic oncologists should screen their patients for co-

BARNHILL ET AL.

Ion cancer. Sixty-one (65%) believe it is their responsi- bility to inquire into the smoking habits of their patients. Forty-five (48%) believe they should be responsible for monitoring their patients for calcium supplementation. Thirty-eight (40%) believe they should monitor their pa- tients’ cholesterol levels. Twenty-one (22%) think it is their responsibility to monitor their patients for vitamin supplementation.

DISCUSSION

Follow-up guidelines for patients after the completion of therapy for a gynecologic malignancy have not been defined. In fact, the surveillance routine for patients en- rolled in specific treatment or monitoring protocols has rarely been reported. In a study concerning the moni- toring of circulating tumor markers in patients with a gynecologic malignancy, Schwartz reported that, after a negative second-look operation, his ovarian cancer pa- tients were followed monthly for the first year, every 3 months during the second year, every 4 months during the third year, every 6 months during the fourth and the fifth years, and then annually [l]. In the same report, patients who had completed treatment for a cervical or an endometrial cancer were seen every 3 months during the first year, every 4 months during the second year, every 6 months during the third through fifth years, and then annually. The extent of the patients’ evaluations during each of those visits was not detailed. In a study of cervical cancer patients, Look indicated that her pa- tients were followed every 3 months for the first 2 years after the completion of therapy, every 6 months for the next 3 years, and then annually [2]. A pap smear and pelvic examination were done at each visit. X-ray pro- cedures were performed only if the patients developed signs or symptoms suggestive of recurrent disease. Arian- Schad, in a study of stage III ovarian cancer patients, stated that those women were examined every 3 months at which time they had a CT scan, chest X ray, IVP, abdominal ultrasound, physical examination, blood chem- istries, and tumor markers [3]. Although the extent of the evaluations was not detailed, in a study of stage II ovarian cancer patients, Piver indicated that he followed those women monthly until progression or death [4].

In this follow-up survey, the majority of respondents examine their asymptomatic, disease-free patients every 3 months during the first year after completing therapy, every 3 or 4 months during the second year, every 6 months during the following 3 years, and then annually after this initial 5-year period. The majority of the gy- necologic oncologists surveyed recommend that the ex- amination include the breasts, abdomen, lymph nodes, and pelvis. A pap smear and stool guaiac are also done

at each of those visits. The majority of the survey re- spondents obtain a chest X ray yearly for the first 3 years following completion of therapy. Based on the median response of the study group, patients who had a previ- ously elevated CA-125 or ovarian germ cell tumor marker should have it checked on a schedule that would coincide with each clinic visit during the first 5 years of follow-up. There is no clear consensus recommendation for tumor marker surveillance after the initial 5-year period.

Once a woman begins routine follow-up by a gyneco- logic oncologist, she may expect to receive all of her gynecologic care during those clinic visits. In fact, 61 (65%) of the survey respondents who answered the ques- tion concerning routine gynecologic care indicated that they are the only source of gynecologic care for their patients. In this primary care role, basic medical deci- sions, including whether to prescribe calcium supplemen- tation, may need to be addressed by gynecologic oncol- ogists. The development and rate of progression of osteoporosis appear to be related to many factors in- cluding smoking, excessive alcohol ingestion, immobili- zation, exercise, vitamin D intake, and hormone status [5]. The effect of calcium supplementation, as an inde- pendent factor, on preventing or slowing the progression of osteoporosis remains somewhat controversial; how- ever, the recent literature continues to recommend cal- cium supplementation for postmenopausal women [6]. Al- though the dose varied, 56 (60%) of the survey respondents prescribe calcium supplementation for their postmenopausal patients.

Heart disease is the leading cause of death in the United States [7]. Since the serum cholesterol level is directly proportional to the cardiac death risk, the American Col- lege of Physicians recommends the cholesterol be checked every 5 years after age 20 [8,9]. Fifty-eight (62%) of the survey respondents monitor their patients’ cholesterol levels.

No major medical organization suggests vitamin sup- plementation for apparently well-nourished healthy adults [9]. Although controversial, some physicians routinely recommend vitamin supplementation to those with a his- tory of cancer; however, 65 (69%) of the survey respond- ents do not prescribe vitamins for their patients.

Lung, breast, and colon cancers cause the majority of cancer deaths among women [7]. Although no specific screening has been recommended for lung cancer [9], physicians should encourage the cessation of smoking. Sixty-eight (72%) of the survey respondents address the issue of smoking with their patients. There are established guidelines for breast cancer screening. In addition to breast self-examinations and regular breast examinations by a physician, the American College of Obstetricians and Gynecologists (ACOG) recommends obtaining a mammogram at age 35-40, every l-2 years from age 40-

CLINICAL SURVEILLANCE OF GYNECOLOGIC CANCER PATIENTS 279

TABLE 5 Comparison of the Beliefs of Gynecologic Oncologists for Screening and Monitoring Their Patients for Issues not Directly Related

to a Gynecologic Malignancy

Screening parameter

Breast cancer Colon cancer Smoking cessation Calcium use Cholesterol level Vitamin use

Respondents who are the only source of gynecologic care for

their patients Number (%)

58 (95%) 48 (79%) 45 (74%) 32 (52%) 29 (48%) 19 (31%)

Respondents who are not the only source of gynecologic care

for their patients Number (%)

2.5 (86%) 1.5 (52%) 13 (45%) 10 (34%) 7 (24%) 2 (7%)

P = 0.206 (ns) P = 0.014’ P = 0.009* P = 0.121 (ns) P = 0.040* P = 0.015*

* By Fisher’s exact test, P < 0.05. Note. ns, not significant.

49, and then yearly after age 50 [lo]. Ninety-one (97%) of the survey respondents order mammograms on a reg- ular basis. Although screening for colon cancer is highly controversial [ 11,121, ACOG recommends a yearly digital rectal examination beginning at age 40 and a yearly stool guaiac after age 50 [lo]. Ninety-four (100%) of the re- spondents perform a rectal examination at each clinic visit, and 48 (51%) check a stool guaiac with each ex- amination. ACOG also recommends sigmoidoscopy every 3-5 years after age 50 following 2 consecutive negative yearly examinations [lo]; however, only 20 (21%) of the respondents follow that recommendation. Forty-seven (50%) of the survey respondents never order surveillance sigmoidoscopy for their follow-up patients. This lack of compliance with the published recommendations for sig- moidoscopy should be reassessed.

The 61 respondents who are the only source of gyne- cologic care for their patients are more likely to believe that gynecologic oncologists should be responsible for screening their patients for colon cancer, smoking ces- sation, cholesterol level, and vitamin use than the 29 respondents who are not the only source of gynecologic

care for their patients (Table 5). There is no difference between the two groups concerning beliefs about respon- sibility for monitoring for breast cancer or calcium use, two issues usually addressed by gynecologists. In actual clinical practice, there is no significant difference between these two groups when it comes to ordering mammograms or sigmoidoscopy, discussing the smoking habits of their patients, prescribing calcium or vitamins, or checking cho- lesterol levels (Table 6).

Several major medical organizations make recommen- dations concerning the monitoring of the American pop- ulation for cholesterol determinations, smoking cessation, breast cancer screening, and colon cancer surveillance [9,10]. None of these organizations, however, suggest whose responsibility it is to carry out those recommen- dations. Since gynecologic oncologists or their designees will be examining asymptomatic, disease-free follow-up patients frequently, it is understandable that gynecologic oncologists may be perceived as primary care providers for this group of patients. This survey underscores that fact since respondents who are the only source of gyne- cologic care are also more likely to feel responsible for

TABLE 6 Comparison of the Actual Practices of Gynecologic Oncologists in Screening and Monitoring Their Patients for Issues Not

Directly Related to a Gynecologic Malignancy

Respondents who are the only source of gynecologic care for

their patients; Screening parameter number (%)

Regular mammograms Regular sigmoidoscopy Smoking cessation Prescribe calcium Check cholesterol level Vitamin use

59 (97%) 30 (49%) 46 (75%) 36 (59%) 41 (67%) 23 (38%)

Respondents who are not the only source of gynecologic care

for their patients; number (%)

29 (100%) 13 (45%) 19 (66%) 17 (59%) 15 (52%) 5 (17%)

P = 1.000 (ns) P = 0.822 (ns) P = 0.450 (ns) P = 1.000 (ns) P = 0.171 (ns) P = 0.056 (ns)

Note. By Fisher’s exact test; ns, not significant.

280 BARNHILL ET AL.

TABLE 7 Current Opinion Regarding the Clinical Follow-up of Asymp

tomatic, L%ease-free Women with a History of a Gynecologic Cancer

Frequency of clinic visits

Examinations and tests to be performed at each visit

Surveillance X-ray procedures

Frequency of CA-125 and germ cell marker determinations

Serum cholesterol determinations

Vitamin supplementation Calcium supplementation Smoking habits Mammograms

Sigmoidoscopy

Every 3 months for the first year after therapy

Every 3 or 4 months for the second year

Every 6 months for the third through the fifth years

Yearly after the initial S-year period Breast, abdominal, lymph node, and

pelvic exams Pap smear and stool guaiac Yearly chest X ray for the first 3 years

after therapy Every 3 months for the first 2 years

after therapy Every 6 months for the third through

the fifth years No specific recommendation after the

initial 5-year period Every 5 years or more frequently if

warranted Do not routinely prescribe Prescribe for postmenopausal patients Discuss with the patients Periodically before age 50 Yearly after age 50 No clear recommendation for routine

sigmoidoscopy

monitoring their patients for nongynecologic diseases. This role is very different from the consultant status of the gynecologic oncologist at the time of cancer diagnosis or referral of the patient. Since the majority of women treated for a gynecologic malignancy will be cured of their disease [7], it is reasonable that gynecologic oncologists, as primary care providers for this group, should partici- pate in the recommended monitoring for the diseases for which there exists a substantial mortality risk.

Although the clinical follow-up intervals and the sur- veillance examinations performed at each visit, including X-ray procedures and the frequency of tumor marker determinations, have not been determined for gyneco- logic cancer patients, this survey suggests a feasible clin-

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