Obstetrics & Gynecology:
Secondary Cancer Prevention During Follow-up for Endometrial Cancer
Kwon, Janice S. MD, MPH1; Elit, Laurie MD, MSc2; Saskin, Refik MSc3; Hodgson, David MD4; Grunfeld, Eva MD, DPhil5
From the 1University of British Columbia, Vancouver, British Columbia; 2Juravinski Cancer Centre, Hamilton, Ontario; 3Institute for Clinical Evaluative Sciences, Toronto, Ontario; 4Princess Margaret Hospital, Toronto, Ontario; and 5University of Toronto, Ontario, Canada.
Sponsored through funding from Cancer Care Ontario to evaluate patterns of follow-up cancer care in the province.
Corresponding author: Janice S. Kwon, MD, MPH, FRCSC, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of British Columbia, 2775 Laurel Street, 6th Floor, Vancouver, British Columbia, Canada, V5Z 1M9; e-mail: email@example.com.
The authors did not report any potential conflicts of interest.
OBJECTIVE: To conduct a population-based study of incidence and screening rates for secondary breast and colorectal cancers after endometrial cancer and to assess implications for follow-up.
METHODS: This was a retrospective population-based study from administrative databases. The inception cohort included all women diagnosed with endometrial cancer in Ontario, Canada from 1996 to 2000, without a previous history of breast or colorectal cancer. We ascertained 5-year recurrence and overall survival rates and practitioner type during follow-up. Primary outcomes were age-standardized incidence and screening rates of breast and colorectal cancer during follow-up compared with the general female population.
RESULTS: There were 3,473 women in the cohort. The 5-year recurrence rate was 15.0% and overall survival was 79.3%. Family physicians were most often involved in follow-up care. Age-standardized incidence rates of breast and colorectal cancer were 0.5% and 0.7%, respectively, compared with 0.5% (P=.76) and 0.2% (P<.001) in the general population. Age-standardized screening rates for these cancers were 64.0% and 30.0%, respectively, compared with 31.0% (P<.008) and 15.0% (P<.001) in the general population. Women aged older than 70 years and those with the lowest income were least likely to have secondary cancer screening.
CONCLUSION: Women with endometrial cancer have a comparable risk of breast cancer but higher risk of colorectal cancer compared with the general population. Follow-up after endometrial cancer should include counseling and uptake of secondary cancer prevention strategies, which will contribute to maximizing long-term survivorship for these women.
LEVEL OF EVIDENCE: II
Endometrial cancer is most common gynecologic cancer and the fourth most common cancer affecting women in North America. At present there is no consensus on optimal follow-up for those who have completed treatment. The majority of women have early stage disease and will never experience a recurrence. There may be a family physician, obstetrician–gynecologist, and/or gynecologic oncologist involved in follow-up care at various intervals, but there is no evidence that practitioner type, routine diagnostic tests, or frequency of follow-up has any effect on survival.1–11 However, women with endometrial cancer are known to be at increased risk for breast and colorectal cancer.12–14 For the duration of their follow-up, there may be opportunities for counseling and uptake of secondary cancer prevention strategies such as mammography for breast cancer and fecal occult blood testing or colonoscopy for colorectal cancer. It is unclear if endometrial cancer survivors are counseled about the risks of these secondary cancers and if they undergo appropriate screening. We conducted a population-based study of women diagnosed with endometrial cancer between 1996 and 2000 in the province of Ontario, Canada, and reviewed their follow-up, secondary cancer screening practices, and outcomes to the end of 2006.
MATERIALS AND METHODS
This was a retrospective, population-based study of endometrial cancer from a single-payer, publicly-funded health care system in Ontario, Canada. Ethics approval was obtained from the Research Ethics Board of the Institute for Clinical Evaluative Sciences in Toronto, Ontario, Canada. All electronic records of endometrial cancer (International Classification of Diseases, 10th Revision codes 179 or 182) were identified from the Ontario Cancer Registry from 1996 to 2000 and linked to various administrative databases for demographic information, treatment, and vital statistics to the end of 2006. The methodology for this process has been previously described.15,16 The inception cohort was defined as all women who had surgery for endometrial cancer (at least hysterectomy) from January 1, 1996, to December 31, 2000, who were available for follow-up at least 1 year after their diagnosis and did not have a previous history of breast or colorectal cancer. Tumor histopathology, grade, and extent of disease were obtained directly from pathology files at the Ontario Cancer Registry. Patients were then classified into four risk groups, including three risk groups for early stage disease (stage I and II endometrioid-type histology), and one risk group for advanced stage (stage III and IV) and all nonendometrioid subtypes (including uterine papillary serous carcinoma, clear cell carcinoma, malignant mixed müllerian tumor, and all sarcomas). The three risk groups for early stage disease were defined in a previously published population-based study of endometrial cancer.15 Low risk was defined as stage IA and IB, grades 1 and 2; intermediate risk was defined as stage IA and IB grade 3, stage IC and IIA grades 1 and 2, and stage IIA grade 3 if less than 50% myometrial invasion; and high risk was defined as stage IC grade 3, stage IIA grade 3 if more than 50% myometrial invasion, and all stage IIB. The Ontario Ministry of Health and Long-Term Care Registered Persons Database provided information on socioeconomic status by using median income per neighborhood, adjusted for region in Ontario and divided into quintiles. The Registered Persons Database has administrative information for all beneficiaries of the Ontario Health Insurance Plan, which provides provincially funded health care to all Canadian citizens residing in Ontario. Women were censored if they were no longer residing in Ontario or eligible for Ontario Health Insurance Plan, if they recurred or died, or were diagnosed with another cancer. The follow-up period started 1 year from the date of diagnosis, and it ended 5 years from the date of diagnosis, or sooner if the patient was censored. Data on follow-up included number of clinical visits and practitioner type from Ontario Health Insurance Plan fee codes claimed for medical services. Practitioner type was classified as family physician, obstetrician–gynecologist, gynecologic oncologist, or radiation oncologist. Recurrences were identified by biopsy, or imaging followed by radiotherapy and/or chemotherapy after the first 6 months from the date of diagnosis (because therapy within the first 6 months could still be classified as adjuvant therapy). To evaluate screening practices for breast and colorectal cancer, we obtained data on mammography and colorectal cancer screening, which included fecal occult blood testing, barium enema, sigmoidoscopy, and colonoscopy. Incidence and screening rates for breast and colorectal cancer in the endometrial cancer cohort were compared by χ2 test to the general female population during the same period. We excluded those who underwent colonoscopy within 5 years of endometrial cancer diagnosis, because they would not have required repeat screening for another 10 years (ie, after the 5-year follow-up period). Age-standardized incidence and screening rates for these cancers were compared between the endometrial cancer cohort and general population by the z-test. Statistical analysis was performed with SAS 9.1 (SAS Institute Inc., Cary, NC).
There were 4,471 women with a diagnosis of endometrial cancer in Ontario from 1996 to 2000. There was no information on treatment or pathology for 550 women, and vital statistics were unavailable for an additional 47 women who had surgery in Ontario but resided in another province or state. There were an additional 401 women who either had a history of breast or colorectal cancer or were not available for follow-up at least 1 year after their diagnosis of endometrial cancer. The inception cohort was therefore composed of 3,473 women. The mean (median) age was 63 years, with a range of 18 to 97 years. At the beginning of the second, third, and fourth years of follow-up there were 3,210, 3,044, and 2,894 patients, respectively. The 5-year recurrence rate was 15.0%, and 5-year overall survival was 79.3%.
Table 1 summarizes practitioner visits according to age group. Family physicians were most likely to be involved in patient care during the follow-up period. Approximately 95% of all patients were seen by their family physicians, with an average of 6.8 visits per year. Women aged older than 70 years had more visits with their family physicians than women aged younger than 50 years (mean of 8.3 and 5.4 visits, respectively). Approximately 75% of all patients had at least one visit with a gynecologic oncologist, and women aged younger than 50 years were more likely to see a gynecologic oncologist than women aged older than 70 years (78.1% and 70.5%, respectively). Obstetrician–gynecologists were least likely to be involved in patient care during the follow-up period. Women aged younger than 50 years were more likely to have follow-up with an obstetrician–gynecologist (9.3%) than women aged older than 70 years (4.2%). The mean number of visits with each practitioner type remained comparable across all years of follow-up.
Table 2 summarizes the rates of secondary cancer screening. After excluding women aged younger than 50 years (because breast and colorectal cancer screening had not routinely been recommended for these women in the general population during this time), rates were lowest in women aged older than 70 years (42.9% and 29.8% for breast and colorectal cancer screening, respectively). Women in the highest income quintile were more likely to have at least one mammogram (68%) and colorectal cancer screen (35.1%) than those in the lowest income quintile (58.3% and 31%, respectively). Women with high-risk early stage endometrial cancer were less likely to have mammography (57.3%) and colorectal cancer screening (26.7%) than those with low-risk early stage disease (69.2% and 33.7%, respectively).
Crude incidence rates of breast and colorectal cancer in the endometrial cancer cohort during the follow-up period were 1.0% and 1.4%, respectively, and corresponding rates in the general population were 0.5% and 0.2%, respectively. We calculated age-standardized incidence rates based on the 1st to 99th percentiles for age at endometrial cancer diagnosis (35 to 86 years, respectively) because of the exceedingly low numbers of patients with endometrial cancer beyond these thresholds. The age-standardized incidence rates of breast cancer were comparable between the endometrial cancer cohort and general population (0.5% in both groups, P=.76). However, age-standardized incidence rates of colorectal cancer were significantly different (0.7% and 0.2% in the endometrial cancer cohort and general population, respectively, P<.001). The incidence of colorectal cancer was highest among women diagnosed with endometrial cancer aged younger than 50 years (relative risk of 10 compared with women in the general population aged younger than 50 years). Age-standardized rates of breast cancer screening were 64.0% and 31.0% (P<.008), and age-standardized rates of colorectal cancer screening were 30.0% and 15.0% (P<.001) in the endometrial cancer cohort and general population, respectively. These results are summarized in Table 3.
Routine follow-up after cancer treatment has always been considered essential for early detection of recurrences; however, routine follow-up has not been shown to improve overall survival in endometrial cancer.1–11 Monitoring of treatment-related adverse effects is also an important element of follow-up.3 However, when surgery is the only modality of treatment, overall quality of life is similar to that in the general population,17 18 except for younger women who are rendered infertile and prematurely menopausal.18,19 Adjuvant pelvic radiotherapy may have a short-term negative effect, 20 but the long-term effect on quality of life seems to be negligible.17–19,21,22 Because the majority of women in our study were already postmenopausal at the time of diagnosis (mean age of 63 years), and they had surgery alone without adjuvant radiotherapy or chemotherapy,15 the effect of treatment on quality of life and long-term well-being may have been minimal. Because most women are expected to survive their diagnosis of endometrial cancer without evidence of disease recurrence, follow-up care should address more than the usual signs and symptoms of recurrence.
Increased risks of breast cancer have been previously reported in women with endometrial cancer,12,13 but in our study, women with endometrial cancer had similar rates of breast cancer compared with the general population. However, those with a previous diagnosis of breast cancer were censored from this analysis, and because breast cancer is usually diagnosed at an earlier age than endometrial cancer,23 we may have underestimated the association between these two cancers. On the other hand, colorectal cancer is usually diagnosed at a later age than endometrial cancer.24 In our study, similar to others,12–14 women with endometrial cancer had an increased risk of colorectal cancer across all age groups, especially those aged younger than 50 years. Young women with endometrial cancer who subsequently develop colorectal cancer may have Lynch syndrome,25 and should be counseled about genetic testing.
The goal of any cancer follow-up program is to maximize well-being and survival, and for endometrial cancer, it should include strategies that address competing mortality risks such as breast and colorectal cancer. Secondary cancer screening should be advocated for all endometrial cancer survivors, regardless of age and income. It is important to note that even in our single-payer, publicly-funded health care system, older women and those in the lowest income quintile were less likely to have breast and colorectal cancer screening than younger women and those in the highest income quintile, respectively. According to other Canadian studies, higher socioeconomic status has been associated with higher rates of breast and colorectal cancer screening,26–28 and, universal health coverage does not necessarily translate into equal access to care and uptake of health services.29 Organized screening programs that target specific subpopulations may reduce these disparities in our health care system.30 The rates of breast and colorectal cancer screening in our endometrial cancer cohort were two times higher than in the general population, which suggests an increased awareness of secondary cancer risks. However, these screening rates were still lower than general population rates in the United States.31 Improving uptake of secondary cancer prevention strategies during follow-up may ultimately have greater effect on overall survival than early detection of endometrial cancer recurrences.
This was one of the largest known studies of endometrial cancer follow-up from a single-payer, publicly-funded health care system within a stable population. Less than 2% of the cohort was lost to follow-up over the 5 years. However, there were several limitations of this study. First, we were unable to determine if patients died of endometrial cancer or unrelated causes, because these details were unavailable from administrative databases. If the majority of deaths were attributed to noncancer causes, this would favor greater involvement of the family physician during follow-up to manage these competing mortality risks. Second, we evaluated follow-up only until 5 years after diagnosis, in accordance with recommendations for endometrial cancer follow-up in Ontario,6 and therefore, screening and incidence rates of breast and colorectal cancer may be very different over the long term. There may have been a detection bias for these cancers over the short term, because most of these women were being followed by at least one health care practitioner during this time, who may have facilitated access to investigations such as mammography or colonoscopy. Finally, we did not have information on potential confounders such as ethnicity, body mass index, use of oral contraceptives, hormone replacement therapy, or nonsteroidal antiinflammatory drugs, and therefore we could only calculate age-standardized incidence rates for secondary cancers. Some women with endometrial cancer aged younger than 50 years may have had Lynch syndrome, which would have increased their risk for colorectal cancer, but family history was unavailable in this study.
Over 44,000 women will be diagnosed with endometrial cancer this year in Canada and the United States, and after 5 years approximately 35,000 of them will still be alive.32,33 These endometrial cancer survivors have specific health risks that need to be addressed during their follow-up to maximize long-term survivorship. They continue to be at risk for breast cancer, and they are at increased risk for colorectal cancer, but they do not seem to be undergoing optimal screening for these cancers, especially older women and those with the lowest income. Current recommendations for breast cancer screening in the general population include mammography every 1–2 years after age 40 years,34,35 and for colorectal cancer screening, fecal occult blood testing every 2 years after age 50 years36 or colonoscopy every 10 years or double-contrast barium enema or sigmoidoscopy every 5 years after age 50 years, with more frequent screening in the presence of a known deleterious mutation or significant family history.37 Regardless of health care practitioner, the follow-up visit provides an important opportunity for counseling and uptake of secondary cancer prevention strategies, which will contribute to maximizing long-term survivorship for women with endometrial cancer.
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© 2009 by The American College of Obstetricians and Gynecologists.