Endometrial Cancer

• doxorubicin plus cisplatin
• doxorubicin, cisplatin, and paclitaxel.

In these patients, there was no improvement in survival when paclitaxel was added to the chemotherapeutic regimen, compared with doxorubicin plus cisplatin. Morbidity increased, however, with the addition of paclitaxel.

Patients in this trial underwent surgical resection of all gross disease, with no residual tumor larger than 2 cm. The role of optimal cytoreduction in endometrial cancer has been debated, however. Several studies have pointed to improved survival in women after removal of visible disease to less than 1 to 2 cm in diameter (FIGURE).^9-11 GOG 184 inclusion criteria required surgical resection of gross disease to ≤2 cm in diameter. It is possible that the therapeutic benefit of surgical debulking may have improved outcome in these patients—to the extent that the addition of paclitaxel did not provide appreciable benefit.

FIGURE Debulk gross disease?

The role of optimal cytoreduction in endometrial cancer has been debated. Several studies have pointed to improved survival in women after removal of visible disease to less than 1 to 2 cm in diameter.

Recommendation for practice

Data on adjuvant therapy for endometrial cancer remains conflicting. Women who have advanced-stage or recurrent endometrial cancer should receive chemotherapy—either with doxorubicin, cisplatin, and paclitaxel, or a platinum taxane regimen. The addition of paclitaxel in surgically debulked patients who have undergone radiation treatment does not appear to improve survival.

There is, however, a clear recommendation for paclitaxel in radiation-naïve patients and those who have gross residual disease. Further studies are needed to elucidate the role of radiation therapy in an era of volume-directed radiation.

Look for Lynch syndrome in young women with endometrial cancer

Lu K, Schorge J, Rodabaugh K, et al. Prospective determination of prevalence of Lynch syndrome in young women with endometrial cancer. J Clin Oncol. 2007;25:5158–5164.

Endometrial cancer is part of the spectrum of Lynch syndrome (hereditary nonpolyposis colorectal cancer syndrome). Patients with this autosomal-dominant hereditary cancer susceptibility syndrome may present with colorectal cancer, endometrial cancer, or, more rarely, ovarian cancer. Lynch syndrome derives from germline mutations in DNA mismatch repair genes, most often MLH1, MSH2, and MSH6.¹² Genetic testing for all three genes is available for clinical use.

In the past, screening for Lynch syndrome focused on colorectal cancer, but it is now clear that women who have this disorder have a lifetime risk of developing endometrial cancer that exceeds 40%.¹³

In Lynch syndrome, gynecologic cancer often precedes colon cancer

Women with Lynch syndrome-associated endometrial cancer typically present at a younger age than their syndrome-free counterparts (48 compared with 60 years).¹⁴ Previous retrospective studies demonstrated that 50% of women with Lynch syndrome-associated colon and gynecologic cancers had gynecologic cancer preceding the colon cancer. The average was 11 years earlier for endometrial cancer, which suggests that, if these women could be identified at the time they are given their diagnosis of endometrial cancer, more intensive screening for colon cancer could then be initiated.¹⁵

9% of women who develop endometrial cancer before age 50 have Lynch syndrome

One of the screening criteria for Lynch syndrome-associated colon cancer is age <50 years. In this recent prospective, multicenter study involving 100 women who were diagnosed with endometrial cancer at less than 50 years of age, germline Lynch syndrome mutations were identified in 9% of patients. (In this study, germline mutation testing was performed for MLH1, MSH2, and MSH6 genes by full sequencing, and immunohistochemistry was performed for all three genes. Microsatellite analysis was performed on 95 patients, with five women having insufficient tumor for DNA extraction.)

All women who had a germline mutation had a first-degree relative with Lynch syndrome-associated cancer. The combination of a negative family history for Lynch syndrome and a body mass index greater than 30 was highly predictive of having no Lynch syndrome mutation, with a negative predictive value of 96%.

Recommendation for practice

Patients who have an hereditary cancer syndrome such as Lynch syndrome can begin cancer-prevention screening—and be engaged in that screening—when the syndrome is recognized early. Because women who have endometrial cancer that was diagnosed before they were 50 years old are at significant risk of a germline mutation, they should be offered genetic counseling and testing.