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Hard-to-Treat Uterine Corpus Cancers Increasing

Among all U.S. women, rates of more aggressive non-endometrioid cancer subtypes have been rising rapidly. And trends show marked racial differences and disparities, with higher rates of uterine corpus subtypes and poorer survival among non-Hispanic black women, according to a new study in the Journal of Clinical Oncology.

The analysis, conducted by Megan A. Clarke, PhD, and associates from the National Cancer Institute (NCI) in Bethesda, Maryland, found that hysterectomy-corrected uterine cancer incidence rates increased by approximately 1% per year from 2003 to 2015, with the most rapid increases occurring in non-white women, including Hispanic, Asian, and especially black women. The study used data from the Surveillance, Epidemiology, and End Results (SEER) database to calculate rates of uterine corpus cancers in women ages 30 to 79 overall and by histologic subtype, 5-year age groups, and geographic region.

Endometrioid uterine carcinomas are much more common, have a generally good prognosis, and are strongly associated with obesity and other estrogen-related risk factors. In contrast, uterine corpus carcinomas with non-endometrioid histology such as serous, clear-cell, and papillary carcinomas are more aggressive and less hormone-dependent, with worse outcomes and survival. Sarcomas, which generally arise in the myometrium, are less common and have not been well studied.

Unlike previous studies, the NCI analysis corrected for hysterectomy prevalence using data from the Behavioral Risk Factor Surveillance System (BRFSS) and adjusting for women no longer at risk of developing uterine disease. It noted that hysterectomy-corrected uterine cancer rates in blacks have consistently exceeded those of whites since about 2007.

“The higher incidence in black women is likely due to biological differences but the worse survival suggests differences in access to care and other factors,” Clarke told MedPage Today. She said more research is needed to understand risk factors, improve detection, and promote prevention.

Incidence rates of endometrioid subtypes were stable in non-Hispanic white women over the study period but increased in women of other racial/ethnic groups. By contrast, incidence rates of aggressive, non-endometrioid subtypes have been increasing dramatically over time in all racial and ethnic groups, with an overall increase of 2.9% a year from 2000 to 2015. Among the most common non-endometrioid cancers identified were mixed-cell adenocarcinoma, papillary serous cystadenocarcinoma, and clear-cell adenocarcinoma.

In black women, aggressive subtypes occurred at a rate of 25.9 per 100,000 women over the study period. The corresponding rates per 100,000 were 11.4 for white women, 10.1 for Hispanic women, and 7.5 for Asian and Pacific Islander women. Non-Hispanic blacks also have the lowest 5-year survival rates regardless of stage at diagnosis or histologic subtype.

The NCI analysis aligns with findings from a recent Danish study of hysterectomy-corrected uterine cancer incidence which also showed increasing rates of non-endometrioid but not endometrioid carcinomas.

Overall, Clarke said, the 5-year survival for endometrioid uterine cancer was about 92%, compared with about 58% for non-endometrioid carcinomas. And while these more aggressive histologic subtypes are less common, accounting for 18% of all uterine cancers, the real numbers are high.

By region, the hysterectomy-corrected increase in the incidence rate of non-endometrioid cancers was highest in the South at 90.6% and lowest in the Northeast at 44.9%. As for hysterectomy prevalence, this varied widely by region, with, again, the highest rates in the South and lowest in the Northeast.

Hysterectomy correction decreased regional differences observed using uncorrected rates, suggesting these differences largely reflect regional variation in hysterectomy prevalence rather than true differences in cancer incidence, the authors stated. “Importantly, after stratifying by race and ethnicity, histology, and stage at diagnosis, we did not observe strong regional differences in the survival rates of patients with uterine cancer,” they wrote.

As for risk factors, obesity, diabetes, and changes in hormone use are not thought to play a major role in the uptick in these cancer subtypes, Clarke said since these factors are all associated with endometrioid cancer in which rates for white women have remained stable. “The next stage of research is to better understand the risk factors. But since these cancers are more rare, they’re more difficult to study because we don’t have the numbers.”

Health care providers need to be aware of the rise in the non-endometrioid subtype. “Uterine cancer is generally talked about as having good survival, but the non-endometrioid type is diagnosed at later stages and has worse survival,” Clarke said. “So it’s good for care providers to be mindful that these subtypes are on the rise and pay attention to the histologic subtype.” Postmenopausal patients should be urged to have any abnormal spotting, bleeding, or other vaginal discharges investigated.

The authors acknowledged noted limitations to the study including that response rates to the BRFSS have been lower compared with other surveys, which may lessen the representativeness of the data. In addition, the region-specific hysterectomy prevalence estimates may not completely overlap with SEER catchment areas. Finally, although SEER registries use standardized codes and procedures for classifying race and ethnicity data, initial collection of this information was carried out by healthcare facilities and practitioners, and misclassification is possible.

This work was supported by the Intramural Research of the National Cancer Institute, National Institutes of Health. Clarke disclosed stock and ownership interests in Merck and Johnson & Johnson. Co-authors Devesa and Wentzensen reported interests in or ties to several private-sector organizations.