In Esophageal Cancer, Women Have Stronger Responses

Nick Mulcahy

August 23, 2017

Women have better responses than men to treatment for esophageal cancer, a highly lethal malignancy, according to a new study, which is the largest of its kind.

Unfortunately, the advantage of having higher rates of complete and near complete pathologic responses to neoadjuvant chemoradiotherapy (nCRT) did not translate into greater survival for women.

The patients all had locally advanced esophageal cancer and underwent esophagogastrectomy; this three-pronged multimodality approach is standard of care.

Overall 5-year survival rates were not significantly different for women than for men, but there was a trend toward superior survival among the women (52.1% vs 44%; P = .53).

But this finding, which was "surprising," may be a function of sample size, said senior author K. Robert Shen, MD, a surgeon at the Mayo Clinic in Rochester, Minnesota.

"We believe it is likely that in a larger data set, we would see a statistically significant difference [in survival between women and men]," Dr Shen told Medscape Medical News.

The new study was published online August 22 in the Annals of Thoracic Surgery.

There was other positive news for women from the study ― they were also less likely to experience tumor recurrence than men.

Sex disparity has already been established in some ways with this cancer, suggested Dr Shen.

"Esophageal cancer affects men and women differently, which likely reflects differences in the biology and genetics of the tumor. Men are more at risk to develop this cancer, and women respond better to current treatments for locally advanced esophageal cancer," he said.

The effect of sex hormones (eg, estrogen), present either endogenously or as a result of replacement therapy, may play a role in differences, he added.

Gastric cancer, hepatocellular carcinoma, and colorectal carcinoma are other cancers in which the incidence is much higher in men and in which the survival rate is higher in women, Dr Shen also offered.

Other research has indicated that in esophageal cancer, complete pathologic (CP) response, which is defined as the absence of disease in both the esophagus and the lymph nodes (T0N0) after nCRT and surgery, has clinical relevance, inasmuch as it is associated with improved survival compared to lesser responses.

However, "limited data" exist about sex and the ability to achieve a CP response, say the authors. Hence, the team conducted the new study.

The results of the new study are more meaningful than the results of a study they conducted earlier. In that study, they investigated sex disparity in esophageal cancer outcomes, but the study was underpowered, with too few women (n = 20) to allow comparison to men (n = 142) (Ann Thorac Surg. 2009;87:392-399).

In the new study, the Mayo Clinic team retrospectively investigated 145 female patients who had undergone nCRT followed by surgery from 1990 to 2013 at three Mayo centers (Minnesota, Florida, and Arizona). These patients were compared to 221 male control patients with respect to age, pretreatment clinical stage, histologic type, and surgical era.

The median age for female patients was 64 years; for male patients, it was 61 years.

The methodology employed is important, the investigators note. "Our study is also the only one to use a methodology where female and male patients were matched based on certain characteristics to eliminate possible confounding factors," Dr Shen said in a press statement.

Women were more likely to have a CP response or a nearly complete pathologic (NCP) response to nCRT (84 patients [58%]) compared with men (103 patients [47%]; P = .03).

Recurrence-free survival for women was 71.7% compared with 55.4% among men. The median follow-up time was 4.2 years.

Men had an 80% increased risk for recurrence (hazard ratio [HR], 1.80; 95% confidence interval [CI], 1.15 - 2.68; P = .008) compared to the women.

Also, the study confirmed that a stronger response to induction therapy was associated with improved recurrence-free survival (irrespective of the sex of the patients). Recurrence-free survival for CP response or NCP response was 75.5% (95% CI, 67.8 - 83.0) compared with 44.8% (95% CI, 35.8 - 55.3; P = .001) for a partial pathologic response.

Most of the cancers were adenocarcinomas (72% of the women and 87% of the men). The remainder were squamous cell carcinomas (28% of women and 13% of the men).

The study authors report that nCRT consisted of two cycles of chemotherapy and concomitant radiotherapy. Chemotherapy included 5-fluorouracil administered as a continuous 96-hour infusion (1000 mg/m2, days 1 - 4, weeks 1 and 5) and cisplatin (75 mg/m2/d) as a daily bolus for 1 hour on day 1 of weeks 1 and 5). Concurrent radiotherapy included 28 fractions (180 cGy) 5 d/wk for a total dose of 5040 cGy. A 4- to 6-week recovery period followed nCRT.

No sources of funding for the study have been disclosed. The authors have disclosed no relevant financial relationships.

Ann Thorac Surg. Published online August 22, 2017. Abstract

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