Obstetrics & Gynecology:
Improved Survival of Asians With Corpus Cancer Compared With Whites: An Analysis of Underlying Factors
Zhang, Mallory M. MD1; Cheung, Michael K.1; Osann, Kathryn PhD3; Lee, Marion M. PhD4; Lin Gomez, Scarlett S. PhD5; Whittemore, Alice S. PhD2; Husain, Amreen MD1; Teng, Nelson N. MD, PhD1; Chan, John K. MD1
From the 1Division of Gynecologic Oncology, Department of Obstetrics and Gynecology and 2Department of Health and Research Policy, Stanford Cancer Center, Stanford University School of Medicine, Stanford, California; 3Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Chao Family Comprehensive Cancer Center, University of California, Irvine–Medical Center, Orange, California; 4Department of Epidemiology and Biostatistics, Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California; and 5Northern California Cancer Center, Union City, California.
Corresponding author: John K. Chan, MD, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, 300 Pasteur Drive, HH333, Stanford, CA 94305; e-mail: firstname.lastname@example.org.
OBJECTIVE: To compare the clinicopathologic prognosticators and survival of Asians and whites with corpus cancer.
METHODS: Demographic, clinicopathologic, and survival data were obtained from the 1992–2001 Surveillance, Epidemiology, and End Results Program. Statistical analyses were performed by Kaplan-Meier methods and Cox proportional hazards model.
RESULTS: A total of 2,144 Asians and 32,999 whites with corpus cancer were identified. The age-adjusted incidence of uterine cancer in Asians compared with whites was 16.8 compared with 26.1 per 100,000. Asians presented at a younger age (mean 58.4 years compared with 65.1; P < .01) and with more advanced stage disease than whites (21.5% compared with 15.4%; P < .01). The 5-year survival rate for Asians was 79.4% compared with 75.2% for whites (P < .01). Asians with stage I-II and III-IV cancers had 5-year survival rates of 89.3% and 41.2% compared with 82.3% and 34.0% for the whites, respectively (P < .01, early stage; P < .01, advanced stage). The survival advantage of Asians persists in endometrioid (P < .01) and uterine papillary serous carcinomas (P < .01), but not in clear cell carcinoma (P = .62) or sarcomas (P = .78). In multivariate analysis, younger age (P < .01), earlier stage (P < .01), favorable histology (P < .01), and lower grade (P < .01) remained as significant independent prognosticators for improved survival. However, race was not an important prognosticator.
CONCLUSION: The overall survival advantage experienced by Asians with uterine cancer is attributable to their younger age at diagnosis. Because Asian women present at a younger age with more advanced disease, physicians should have an increased index of suspicion for malignancy in young Asian women with suspicious symptoms and consider a lower age threshold for biopsy in this group.
LEVEL OF EVIDENCE: II-2
Uterine cancer is the most common gynecologic malignancy in the United States. According to the latest data from the National Cancer Institute, approximately 40,000 new cases and 7,000 deaths from uterine cancer are expected in 2004.1 Although racial differences in the incidence and survival from uterine cancer have been previously published, most of these studies have focused on disparities between African Americans and whites. Both population and institutional studies have demonstrated that African Americans have a significantly lower risk of developing uterine cancers but have worse outcomes.2–4 Recent research efforts have focused on distinguishing the underlying factors responsible for the survival discrepancy between racial groups, including demographic, socioeconomic, genetic, clinicopathologic, and treatment differences.
Limited information is currently available on whether racial disparities exist between Asians and whites. Although lower rates of uterine corpus cancer have been reported in Asian countries, it is unclear whether this difference persists for Asians in the United States.5 Some authors have postulated on the possible role of phytoestrogens in the soy-rich Asian diet, as well as the lower incidence of obesity, as contributing factors to the lower rates of uterine cancer in this population.6–8 On the other hand, 1 recent study showed that Asian or Pacific Islander race is a significant independent predictor for decreased survival in endometrial cancer.9
In this large population-based study of 35,143 uterine cancer patients, we compared the incidence and survival of Asians to whites. More specifically, we analyzed the clinicopathologic prognostic factors that can contribute to the differences in survival.
Demographic, clinicopathologic, treatment, and survival information of these 2 groups of patients during the period from January 1, 1992, to December 31, 2001, were extracted from the Surveillance, Epidemiology and End Results (SEER) database of the United States National Cancer Institute. Data are reported from 9 population-based registries that represent approximately 14% of the U.S. population and include Utah, Hawaii, Iowa, New Mexico, Connecticut, Alaska, and the metropolitan regions of Detroit, San Francisco and Oakland, Seattle, Atlanta, San Jose and Monterey, and Los Angeles.10 Asian race in this study was defined as Chinese, Japanese, Filipino, Korean, and Vietnamese. Histology of disease was classified into 4 categories: endometrioid carcinoma, uterine papillary serous carcinoma, clear cell carcinoma, and sarcomas.
Statistical analysis was performed using the Intercooled STATA 8.0 program (StataCorp LP, College Station, TX). Demographic, clinicopathologic, and treatment data, including differences in age, stage of disease, and histology, were compared using the χ2 test. Survival analysis by race, age, stage, and histology were performed using Kaplan-Meier estimates of survival probability. The Cox proportional hazards model was used to identify independent predictors of survival. Factors included in the multivariate analysis included age at diagnosis, race, stage of disease, grade of disease, and histologic cell type. A 2-tailed P < .05 was considered statistically significant. A comparison of the age distributions of Asian and white women with uterine cancer was also performed.
A total of 2,144 Asian and 32,999 white women with uterine cancer were identified. The age-adjusted uterine cancer incidence was 16.8 for Asians as compared with 26.1 for whites per 100,000 women. The type of treatment received was similar for Asians and whites (P = .18). The 5-year overall survival rate for Asians was 79.4% compared with 75.2% for whites (P < .01; Fig. 1). When matched for stage of disease, the 5-year overall survival rate of Asians was significantly better compared with whites at 89.3% compared with 82.3% (P < .01) for stage I-II disease, and 41.2% compared with 34.0% (P < .01) for stage III-IV disease (Fig. 2). Disease-specific survival rate in Asians and whites was 95.5% compared with 93.8% (P < .01) in stage I-II disease and 55% compared with 49.3% (P = .02) in stage III-IV, respectively.
The demographic and clinicopathologic characteristics are shown in Table 1. The mean age of Asians was 58.4 years as compared with 65.1 years for whites (P < .01). Asian women presented at a significantly younger age than whites across all stages of disease. In fact, the mean age of Asians compared with whites diagnosed with stage I, II, III, and IV corpus cancer was 57.8 years compared with 64.5 years (P < .01), 55.5 years compared with 66.8 years (P < .01), 60.0 years compared with 66.2 years (P < .01), and 61.7 years compared with 67.3 years (P < .01), respectively. Furthermore, for all histologic groups, Asians were significantly younger than whites, with a mean age of 57.8 years compared with 64.8 years (P < .01) for endometrioid, 63.8 years compared with 69.8 years (P < .01) for uterine papillary serous carcinoma, 60.4 years compared with 69.1 years (P < .01) for clear cell carcinoma, and 58.5 years compared with 63.2 years (P < .01) for sarcomas, respectively. Asians were also significantly younger than whites matched for grade of disease, with a mean age of 55.4 years compared with 63.0 years for grade 1 (P < .01), 58.1 years compared with 65.2 years for grade 2 (P < .01), and 61.9 years compared with 67.9 years for grade 3 disease (P < .01). Of the 32,999 white patients in this database, 229 (0.69%) were diagnosed with uterine cancer younger than age 35 compared with 46 (2.15%) of 2,144 Asian patients. In other words, approximately 1 of 50 Asian patients compared with 1 of 150 white patients was younger than age 35—the age threshold currently recommended to perform endometrial evaluation for abnormal bleeding. However, Asians were more likely to be diagnosed with stage III-IV disease compared with their white counterparts (21.5% compared with 15.4%; P < .01).
Both the overall (89.31% compared with 73.53%, < 50 years and ≥ 50 years, respectively) and disease-specific (93.73% compared with 86.93%, < 50 years and ≥ 50 years respectively) 5-year survival rates of younger women were significantly better than older women (P < .01; Fig. 3). However, when survival analysis is performed controlling for age, the survival advantage experienced by Asians is no longer seen. In fact, in some age groups, Asians have either a statistically significantly worse or a trend toward worse survival than whites. Specifically, the disease-specific survival rate of Asians compared with whites is 91.6% compared with 94% (P = .06) for those < 50 years, 88.9% compared with 93.3% (P < .01) for 50 years to 59 years, 88% compared with 89.5% (P = .48) for 60 years to 69 years, 81.7% compared with 84.1% (P = .24) for 70 years to 79 years, and 78.4% compared with 75.8% (P = .76) for ≥ 80 years.
There was a significantly higher proportion of Asians diagnosed with sarcomas of the uterus compared with whites (9.4% compared with 7.2%; P < .01). The 5-year survival rate for Asians was significantly higher than whites diagnosed with endometrioid carcinoma (85.2% compared with 79.7%, P < .01) and uterine papillary serous carcinoma (63.6% compared with 48.6%, P < .01). On the other hand, no significant survival differences were found between whites and Asians for clear cell carcinomas (48.9% compared with 56.7%, P = .62) and sarcomas of the uterus (44.7% compared with 46.7%, P = .78). In grade 1 and 2 disease, Asians survived significantly better than whites at 93.6% compared with 88.9% (P < .01) and 86.9% compared with 79.2% (P < .01). However, differences in survival were not statistically different in those with grade 3 disease (P = .45).
On multivariate analysis, age at diagnosis, stage of disease, histologic cell types, and grade of disease all remained as significant prognostic factors for survival in Asians and whites (Table 2). Asian race was a good prognosticator only if the age at diagnosis variable is excluded from the multivariate analysis. However, when adjusted for age at diagnosis, race as a predictor of survival becomes insignificant. Thus, the overall survival advantage experienced by Asian women with uterine cancer is attributable to their younger age at the time of diagnosis.
Cancer of the uterine corpus is the most common gynecologic malignancy. Racial differences in the occurrence of uterine cancers have long been documented but continue to be poorly understood. In our study, the age-adjusted incidence of uterine corpus cancer was 16.8 for Asians as compared with 26.1 for whites per 100,000 women. This echoes a previous report by Plaxe and Saltzstein,11 who found a significantly lower incidence of both low- and high-grade endometrial cancer for Asians as compared with whites using data from the California Cancer Registry. Additionally, Liao et al5 reported the incidence of endometrial cancer to be highest in whites, lower in U.S.-born Asians, and lowest in Asian-Americans born in Asia. This suggests possible geographic and cultural differences in the exposure to risk factors for the development of uterine cancer that may include obesity, use of hormone replacement therapy, and dietary patterns. Asian diets consists of high levels of phytoestrogens, which are reported to have antiestrogenic properties that may decrease the risk of endometrial cancer.8 A study of dietary patterns in a multiethnic Hawaiian population demonstrated that high consumption of soy and fiber may protect against the development of endometrial cancer.7,8 The lower rates of obesity among Asians may also play a role in the lower incidence of uterine cancers.6
The 2004 National Cancer Institute’s Cancer Statistics reported that minority populations were more likely to present with distant-site disease for most cancers.1 Multiple institutional and population-based studies have confirmed this finding among African Americans with uterine cancer, and have linked this association to the higher mortality rates found in this group of patients.4,12 Our report demonstrated a similar tendency for Asians to present with more advanced stages of disease compared with whites. These findings may be attributed to barriers to access to care or more aggressive tumor biology in Asians. In an analysis of the Department of Defense database, Kost et al9 did not find a significant difference in the stage at presentation between Asian or Pacific Islanders and whites. It is possible that the equal access to care system of the Department of Defense may not have the barriers to health care access that may be encountered by some minority groups in the general civilian health care systems. Therefore, the differences in stage at presentation between Asians and whites observed in our study was not seen in the Department of Defense series.
Serous papillary, clear cell carcinomas, and sarcomas of the uterus generally carry a worse prognosis than endometrioid adenocarcinomas. Plaxe and Saltzstein11 found that African Americans were more likely to have high-risk histologic types. Several studies have also noted a higher incidence of sarcomas in African Americans as compared with whites, which may contribute to lower survival rates among African Americans.2,13 In our study, sarcomas also represented a slightly higher percentage of all uterine cancers for Asians as compared with whites. Endometrioid adenocarcinoma was proportionally lower in the Asian population than whites. Small, but statistically significant differences in rates of uterine papillary serous and clear cell carcinomas, as well as grades of disease, were also noted between Asians and whites. However, the statistical significance of such marginal differences more likely represents an artifact of such a large database, rather than any clinically relevant difference.
Age has a significant effect on prognosis in cancers of the uterine corpus. Multiple studies have documented decreased survival rates for older patients with endometrial cancer.14–17 Although a probable higher rate of non–cancer-related death in older patients may contribute to lower overall survival, the significant difference in disease-specific survival rate between patients aged younger than 50 years and 50 years or older would suggest that other factors are also involved. There have also been extensive reports of the association between older age and other negative prognostic variables, such as deep myometrial invasion, aggressive histologies, higher grade, and more advanced stage of disease.14,15 Some reports have also postulated that older patients are treated less aggressively than younger women, which may contribute to the decreased survival rate found in the older age group.18 The current literature on uterine cancers contains contradicting reports of whether older age is intrinsically a poor prognosticator or simply a reflection of other high-risk prognostic variables. The results of our multivariate analysis confirm the inverse relationship between age and survival in uterine cancers for both Asians and whites.
In this current study, Asians had a significantly better survival rate compared with whites and controlled for stage of disease and histology. In contrast, another report found that Asians and Pacific Islanders had a significantly decreased survival compared with whites.9 The findings in their study may reflect the institutional selection of patients within the Department of Defense. This current report describes the outcomes of over 35,000 women with uterine cancer in the United States. Furthermore, the SEER database is based on 9 population registries that represent 14% of the overall population.10 Thus, patients selected from these registries closely resemble the demographics of the majority of women in the United States.
It is surprising that Asians have better survival than whites despite presenting with more advanced stage disease and higher rates of sarcomas. This survival advantage is not observed, however, when survival analysis is performed controlling for age. In fact, Asians actually have a trend toward worse survival in several age groups. In multivariate analysis, stage of disease, histology, and grade were all significant independent prognostic factors for survival. Although race was a significant prognosticator of survival on univariate analysis, the survival benefit associated with Asian race disappeared after adjusting for age in multivariate analysis. Therefore, the younger age of Asians with uterine cancer is the major contributor to their improved survival compared with whites.
It is not entirely clear why Asians with uterine cancer in the SEER registry present at a younger age than whites. A similar finding was found by Diaz-Montes and colleagues,19 who noted younger age at presentation for Hispanic women with uterine cancers. One possible explanation is an immigration effect—younger people are more likely to immigrate than older, making the minority population within the United States generally younger than whites. The 2000 U.S. census data showed the median age of Asian-Americans to be 33.8 years compared with 38.9 years for whites.20 However, the median age of the 832 Chinese patients in the Shanghai Endometrial Cancer Study was 55.3 years, which is substantially younger than both Asian-Americans and whites in our study.21 This would suggest that inherent difference in tumor biology may also play a role.
The current recommendation from the American College of Obstetrics and Gynecology22 states that an endometrial assessment should be performed on any women older than 35 years with abnormal uterine bleeding. However, our data showed that the proportion of Asian women aged younger than 35 years diagnosed with uterine cancer in the SEER database is 3 times higher than that of whites. In fact, our data show that approximately 1 of 50 Asians with uterine cancer was diagnosed younger than the age of 35 years compared with only 1 of 150 whites; thus, the data from this study suggest that physicians should consider using a lower age threshold for performing endometrial assessments on Asian women with abnormal uterine bleeding. More specifically, to improve the detection of uterine cancer in Asians to the level of the whites, physicians would need to decrease the suggested age threshold from 35 to 30 years for Asian women.
Our study was limited by the lack of information on surgeon specialty, extent of residual disease, adjuvant chemotherapy, subsequent cytoreductive surgeries, and no central pathology review. Detailed clinical information such as family history, presenting symptoms, and time from symptom to presentation for care that may help to enhance our understanding of the underlying causes of the racial disparities discussed here were also not available. The strength of this study lies in the large number of patients with broad racial distribution, offering the ability to perform detailed, stratified analyses without sacrificing statistical strength. Additionally, this current study is 1 of the largest studies to date of nonselected patients spanning across 12 U.S. regions, allowing for the minimization of selection and surveillance biases often associated with clinical trials and studies from single academic institutions. Because this study was population-based, generalizability of our data to the larger United States population can be justified.
As 1 of the most extensive analyses of Asian women diagnosed with corpus cancer, we found that Asian women presented at a younger age but with more advanced disease. Our findings suggest that physicians should have a higher index of suspicion for malignancies in younger Asians with abnormal bleeding.
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© 2006 The American College of Obstetricians and Gynecologists