Clinical Review

Endometrial Cancer

OBG Manag. 2008 July;20(7):35-42

IN THIS ARTICLE

Is lymphadenectomy always necessary?
When chemotherapy is warranted
Look for Lynch syndrome in young women who have endometrial cancer

References

1. Fanning J, Hoffman ML, Andrews SJ, Harrah AW, Feldmeier JJ. Cost-effectiveness analysis of the treatment for intermediate risk endometrial cancer: postoperative brachytherapy vs. observation. Gynecol Oncol. 2004;93:632-636.

2. Schink JC, Rademaker AW, Miller DS, Lurain JR. Tumor size in endometrial cancer. Cancer. 1991;67:2791-2794.

3. Case AS, Rocconi RP, Straughn JM Jr, et al. A prospective blinded evaluation of the accuracy of frozen section for the surgical management of endometrial cancer. Obstet Gynecol. 2006;108:1375-1379.

4. Horowitz NS, Peters WA, 3rd, Smith MR, Drescher CW, Atwood M, Mate TP. Adjuvant high dose rate vaginal brachytherapy as treatment of stage I and II endometrial carcinoma. Obstet Gynecol. 2002;99:235-240.

5. Mariani A, Webb MJ, Keeney GL, Haddock MG, Calori G, Podratz KC. Low-risk corpus cancer: Is lymphadenectomy or radiotherapy necessary? Am J Obstet Gynecol. 2000;182:1506-1519.

6. Randall ME, Filiaci VL, Muss H, et al. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol. 2006;24:36-44.

7. Fleming GF, Brunetto VL, Cella D, et al. Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol. 2004;22:2159-2166.

8. Alvarez Secord A, Havrilesky LJ, Bac-Jump V, et al. The role of multi-modality adjuvant chemotherapy and radiation in women with advanced stage endometrial cancer. Gynecol Oncol. 2007;107:285-291.

9. Bristow RE, Zerbe MJ, Rosenshein NB, Grumbine FC, Montz FJ. Stage IVB endometrial carcinoma: the role of cytoreductive surgery and determinants of survival. Gynecol Oncol. 2000;78:85-91.

10. Bristow RE, Santillan A, Zahurak ML, Gardner GJ, Giuntoli RL, 2nd, Armstrong DK. Salvage cytoreductive surgery for recurrent endometrial cancer. Gynecol Oncol. 2006;103:281-287.

11. Lambrou NC, Gómez-Marín O, Mirhashemi R, et al. Optimal surgical cytoreduction in patients with Stage III and Stage IV endometrial carcinoma: a study of morbidity and survival. Gynecol Oncol. 2004;93:653-658.

12. Peltomaki P, Vasen HF. Mutations predisposing to hereditary nonpolyposis colorectal cancer: database and results of a collaborate study. The International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer. Gastroenterology. 1997;113:1146-1158.

13. Dunlop MG, Farrington SM, Carothers AD, et al. Cancer risk associated with germline DNA mismatch repair gene mutations. Hum Mol Genet. 1997;6:105-110.

14. Vasen HF, Mecklin JP, Khan PM, Lynch HT. The International Collaborative Group on HNPCC. Anticancer Res. 1994;14:1661-1664.

15. Lu KH, Broaddus RR. Gynecological tumors in hereditary nonpolyposis colorectal cancer: we know they are common—now what? Gynecol Oncol. 2001;82:221-222.

Fast Track

Clear guidelines are lacking on the assessment of lymphatic dissemination and on the anatomic extent of this assessment

Women undergoing lymphatic assessment for endometrial cancer should undergo full systematic lymph-node dissection, not sampling

Women who have advanced or recurrent endometrial cancer should receive chemotherapy with doxorubicin, cisplatin, and paclitaxel or a platinum taxane regimen

The authors report no financial relationships relevant to this article.

Postmenopausal bleeding is a symptom evaluated often by general gynecologists. It necessitates assessment of the endometrium, most often by tissue sampling. When endometrial cancer is confirmed by biopsy, management becomes complex. Should the patient be referred to a gynecologic oncologist? What kind of surgery does she need? What kind of adjuvant treatment will be offered? Could the diagnosis be part of a genetic cancer syndrome?

Recent studies have yielded new information:

Preoperative, intraoperative, and postoperative care by a gynecologic oncologist significantly lowers the cost of health care
Lymphadenectomy for endometrial cancer remains controversial, and may be unnecessary in low-risk patients
Chemotherapy plays an expanding role in the treatment of endometrial cancer. Adjuvant therapy with doxorubicin, cisplatin, and paclitaxel is the treatment of choice for patients who have advanced-stage disease
Nine percent of women who are given a diagnosis of endometrial cancer before 50 years of age have a germ-line Lynch syndrome-associated mutation, which demonstrates that heredity is an important aspect of endometrial cancer and should be considered at all times.

It’s good economics to refer patients to gyn oncology sooner, not later

Hoekstra A, Singh DK, Garb M, Arekapudi S, Rademaker A, Lurain JR. Participation of the general gynecologist in the surgical staging of endometrial cancer: analysis of cost and perioperative outcomes. Gynecol Oncol. 2006;103:897–901.

Early-stage endometrial cancer is often curable with surgery alone because a full 88% of endometrial cancers present as clinical stage I.¹ The role of the general gynecologist in surgical management of these cases is controversial; at some institutions, the practice is to call in the gynecologic oncologist for lymph-node sampling or when gross disease is identified; at others, the standard is to refer the patient to gynecologic oncology as soon as malignancy is diagnosed by endometrial biopsy. Hoekstra and colleagues have attempted to shed light on this issue with a retrospective chart review of 121 patients who were treated at one institution from 1998 to 2000.

Costs of early treatment by a gynecologic oncologist were lower than without referral

The authors performed a retrospective analysis of a group of women with clinical stage-I endometrial cancer who were treated surgically at Prentice Women’s Hospital in Chicago.

The cohort was divided in two:

Group 1 comprised patients who underwent surgery with a general gynecologist, who consulted a gynecologic oncologist intraoperatively
Group 2 comprised patients who were referred to a gynecologic oncologist before surgery and underwent the procedure with a gynecologic oncologist.

Overall, subjects in both groups were similar in age, distribution of surgical stage, need for lymphadenectomy, and length of follow-up.

Group 2 had a significantly shorter operative time overall, and shorter total time in the operating room. Cost per procedure was also significantly lower in this group, in terms of cost to the payer and the physician’s charge. Perioperative costs were also lower in Group 2.

No difference was observed in postoperative outcome. Total hospital costs and lengths of stay were also similar.

Recommendation for practice

With health-care costs rising, be aware of referral strategies that promote cost containment. Women who have endometrial cancer may benefit from the early involvement of a gynecologic oncologist.

Is lymphadenectomy necessary when risk of metastasis is low?

Mariani A, Dowdy S, Cliby W, et al. Prospective assessment of lymphatic dissemination in endometrial cancer: a paradigm shift in surgical staging. Gynecol Oncol. 2008;109:11–18.

The need for surgical staging of endometrial cancer has been recognized since surgical staging criteria were adopted by the International Federation of Gynecology and Obstetrics (FIGO) in 1988. Staging includes hysterectomy, bilateral salpingo-oophorectomy, and biopsy of any gross disease. Clear guidelines on the assessment of lymphatic dissemination and the anatomic extent of this assessment are, however, still lacking.

Proponents of systematic pelvic and para-aortic lymph-node dissection for patients with endometrial cancer cite:

the 15% risk of lymph-node metastasis in women who have tumors 2 cm or larger in diameter²
poor correlation between frozen-section grade and myometrial invasion with final pathology³
the potential therapeutic benefit of the procedure.⁴

Opponents of such lymph-node dissection argue that women who have grade-1, stage-I disease will be overtreated if standardized lymphadenectomy is adopted.

Several retrospective studies have explored this question, with varying results. A large, prospective, randomized trial evaluating lymphadenectomy in clinical stage-I patients (ASTEC trial) has been completed, but is yet to be published.