Correspondence

Endometrial Carcinoma

N Engl J Med 1997; 336:1388-1389May 8, 1997

Article

To the Editor:

In his excellent review of endometrial carcinoma (Aug. 29 issue),1 Dr. Rose correctly describes the important etiologic role of unopposed estrogen, pointing out that “excessive estrogen is associated with most of the risk factors that have been linked to endometrial carcinoma.” However, in the section on screening, Dr. Rose fails to discuss a plasma or saliva assay for estrogen and progesterone. It is the ratio of estrogen to progesterone that determines what level of estrogen is excessive. Prevention being better than early diagnosis of an existing carcinoma, one would think that testing for both hormones should be routine. If estrogen dominance is found, supplementation with progesterone would be preventive.

John R. Lee, M.D.
9620 Bodega Hwy., Sebastopol, CA 95472

1 References

1. 1

   Rose PG. Endometrial carcinoma. N Engl J Med 1996;335:640-649
   Full Text | Web of Science | Medline

To the Editor:

The article on endometrial carcinoma mentions pelvic and para-aortic lymphadenectomy as a treatment when there are poor prognostic factors, such as a grade 3 tumor, middle or deep myometrial invasion, or extension of tumor to the cervix or adnexa. However, lymphadenectomy for endometrial carcinoma in stage I, grade 2 or 3, is controversial. The majority of patients with positive nodes already have occult metastases for which there is no general effective therapy. There is an increase in the rate of complications, and the 10-year results are not improved by this approach.1 The studies2 used as a basis for lymphadenectomy warn against using this method of therapy.

Arno T.M. Verhoeven, M.D., Ph.D.
Rijnstate Hospital, 6800 TA Arnhem, the Netherlands

2 References

1. 1

   COSA-NZ-UK Endometrial Cancer Study Groups. Int J Gynecol Cancer 1996;6:102-107
   CrossRef | Web of Science

2. 2

   Boronow RC, Morrow CP, Creasman WT, et al. Surgical staging in endometrial cancer: clinical-pathologic findings of a prospective study. Obstet Gynecol 1984;63:826-832
   

Author/Editor Response

Dr. Rose replies:

To the Editor: Dr. Lee suggests an interesting concept: since endometrial carcinoma is such a common cancer, estrogen and progesterone testing should be routine for preventive health care. Hanna et al. previously suggested a physiologic assay for excessive estrogen, the progesterone withdrawal test.1 In this procedure patients would be given a dose of oral progesterone, and those with excessive estrogen, who are at high risk for endometrial neoplasia, would have withdrawal bleeding. In their study of 30 postmenopausal patients, 3 of 5 patients with withdrawal bleeding had endometrial hyperplasia, but no cancers were found. A recent case–control study identified high serum levels of estrone, albumin-bound estradiol, and androstenedione (a precursor of estrone) and low levels of sex hormone–binding globulin as risk factors for endometrial cancer.2 Although salivary tests for estrogen and progesterone have been developed, assays for the above-mentioned serum factors are not commercially available. As I mentioned in my article, screening for estrogen-associated tumors (type I), which have an excellent prognosis, may not affect survival in this disease.

Dr. Verhoeven points out the lack of definitive evidence in the literature of a survival benefit associated with lymphadenectomy in endometrial carcinoma. The only study demonstrating increased survival with lymphadenectomy had a variable use of postoperative radiation therapy, which may have explained this outcome.3 However, certain risk factors, including a grade 3 tumor, middle or deep myometrial invasion, or extension to the cervix or adnexa, are associated with an increased risk of nodal metastasis.4 I disagree with Dr. Verhoeven that the presence of occult metastasis may prevent effective therapy. For patients with pelvic-node metastasis and histologically negative aortic nodes, the addition of pelvic radiation therapy has been associated with a survival rate of 72 percent.5

Peter G. Rose, M.D.
University Hospitals of Cleveland, Cleveland, OH 44106

5 References

1. 1

   Hanna JH, Brady WK, Hill JM, Phillips GL Jr. Detection of postmenopausal women at risk for endometrial carcinoma by a progesterone challenge test. Am J Obstet Gynecol 1983;147:872-875
   Web of Science | Medline

2. 2

   Potischman N, Hoover RN, Brinton LA, et al. Case-control study of endogenous steroid hormones and endometrial cancer. J Natl Cancer Inst 1996;88:1127-1135
   CrossRef | Web of Science | Medline

3. 3

   Kilgore LC, Partridge EE, Alvarez RD, et al. Adenocarcinoma of the endometrium: survival comparisons of patients with and without pelvic node sampling. Gynecol Oncol 1995;56:29-33
   CrossRef | Web of Science | Medline

4. 4

   Creasman WT, Morrow CP, Bundy BN, Homesley HD, Graham JE, Heller PB. Surgical pathologic spread patterns of endometrial cancer. Cancer 1987;60:2035-2041
   CrossRef | Web of Science | Medline

5. 5

   Morrow CP, Bundy BN, Kurman RJ, et al. Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study. Gynecol Oncol 1991;40:55-65
   CrossRef | Web of Science | Medline