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Female sex associated with improved survival in HCC
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Women with hepatocellular carcinoma demonstrated longer OS than men, according to results of a SEER analysis.
The benefit was particularly apparent among those 18 to 44 years, as well as those who underwent surgical resection, results showed.
Dongyun Yang, PhD, of the department of preventive medicine at the University of Southern California Norris Comprehensive Cancer Center, and colleagues used the SEER Registry to identify 39,345 patients (76% men) diagnosed with HCC between 1988 and 2010.
Half of the patients were non-Hispanic white, 21% were Asian, 16% were Hispanic, 12% were black and 1% were Native American. The majority (84%) of patients had liver-limited disease, whereas 16% had metastatic disease.
Women were significantly older at the time of HCC diagnosis than men (median age, 67 years vs. 61 years; P˂.001).
Overall, women achieved significantly longer median OS than men (11 months vs. 10 months; HR=0.93; 95% CI, 0.91-0.96).
When researchers stratified data according to age, they observed a greater survival benefit for women aged younger than 55 years compared with men in the same age bracket (HR=0.83; 95% CI, 0.77-0.88). The largest difference in median OS between women and men was observed among those aged 18 to 44 years (14 months vs. 10 months; HR=0.75; 95% CI, 0.65-0.86).
The improvement in survival associated with female sex was observed among those who were non-Hispanic white (P˂.001) or black (P˂.001), but not among those who were Asian (P=.87) or Hispanic (P=.79).
Treatment data were available from 34,674 patients who were diagnosed after 1998. Of these patients, 11% received liver-directed therapy, 11% underwent surgical resection and 7% underwent liver transplantation.
Surgical resection was associated with significantly improved median OS among all women, regardless of age (48 months vs. 44 months; HR=0.87; 95% CI, 0.78-0.96). The benefit was particularly apparent among women aged 18 to 54 years compared with age-matched men (HR=0.68; 95% CI, 0.54-0.86).
“The results of the current study demonstrate that sex influences survival among patients with HCC,” Yang and colleagues concluded. “This is in agreement with preclinical data confirming androgens and estrogens as modulators of hepatic fibrosis, cirrhosis and progression to HCC. It is also consistent with epidemiologic studies demonstrating superior outcomes in younger women with other gastrointestinal cancers. The findings of the current study should be validated in prospective studies that allow for better control of confounding factors and may present unique opportunities for biomarker development and novel therapeutics.”
Disclosure: The study was funded by the NCI. One researcher reports personal fees and a grant from Astex Pharmaceuticals, Bayer, Exelixis, GlaxoSmithKline, Roche/Genentech and Sanofi.
Perspective
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Jimmy Hwang, MD
Yang and colleagues used the SEER database to evaluate the association between gender and survival in patients with hepatocellular carcinoma. Consistent with many other reports, this study demonstrated a clear difference in the incidence of HCC in men and women, and it also suggests that women have better survival outcomes than men. The authors also provide an excellent summary of several biological pathways that could explain these outcomes. However, several methodological limitations of this study must be considered. For example, the SEER database does not include putative etiologies of HCC, such as viral hepatitis, alcohol or nonalcoholic steatohepatitis. This is of particular interest because the authors note a difference in survival between Caucasian and African-American men and women, but not Asian or Hispanic men and women.
The reasons for these differences — or lack of differences — is unclear, but they could be related to differing mechanisms of carcinogenesis (hepatitis B vs. alcohol-induced disease) in the underlying diseases. In addition, the authors reported that women were more likely to have solitary lesions and were more likely to undergo surgery. These variables individually may result in improved survival, but how these important factors may be related to gender or hormones is unclear. Thus, although this study adds further support to the hypothesis that estrogen may result in improved outcomes in HCC, much work to explain and exploit this potential link remains to be undertaken.
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