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Endometrial Cancer Treatment (Professional) (cont.)

Stage I Endometrial Cancer

Standard treatment options:

A total hysterectomy and bilateral salpingo-oophorectomy should be done if the tumor:

  • Is well or moderately differentiated.
  • Involves the upper 66% of the corpus.
  • Has negative peritoneal cytology.
  • Is without vascular space invasion.
  • Has less than a 50% myometrial invasion.

Selected pelvic lymph nodes may be removed. If they are negative, no postoperative treatment is indicated. Postoperative treatment with a vaginal cylinder is advocated by some clinicians.[1]

For all other cases and cell types, a pelvic and selective periaortic node sampling should be combined with the total hysterectomy and bilateral salpingo-oophorectomy, if there are no medical or technical contraindications. One study found that node dissection per se did not significantly add to the overall morbidity from hysterectomy.[2] While the radiation therapy will reduce the incidence of local and regional recurrence, improved survival has not been proven and toxic effects are worse.[3,4,5,6] Results of two randomized trials on the use of adjuvant radiation therapy in patients with stage I disease did not show improved survival but did show reduced locoregional recurrence (3%–4% vs. 12%–14% after 5–6 years' median follow-up, P < .001) with an increase in side effects.[6,7,8][Level of evidence: 1iiDii]

If the pelvic nodes are positive and the periaortic nodes are negative, total pelvic radiation therapy, including the common iliac nodes, should be given. The incidence of bowel complications is approximately 4%, and it can be even higher if the radiation therapy is given after pelvic lymphadenectomy.[9] If the surgery is done using a retroperitoneal approach, the toxic effects are lessened. If the periaortic nodes are positive, the patient is a candidate for clinical trials that could include radiation therapy and/or chemotherapy. Patients who have medical contraindications to surgery should be treated with radiation therapy alone, but inferior cure rates below those attained with surgery may occur.[1,10,11]

Several randomized trials have compared total laparoscopic hysterectomy (TLH) with the standard open procedure, total abdominal hysterectomy (TAH), for patients with early-stage endometrial cancer. Thus far, these reports have been limited to the feasibility of the procedure and quality of life. Feasibility of the laparoscopic approach has been confirmed, although TLH is associated with a longer operative time.[12,13,14] TLH had an improved [12,13] or similar [14] adverse event profile and a shorter hospital stay [12,13,14] when compared with TAH. TLH was associated with less pain and quicker resumption of daily activities,[14,15] although one study found that most of the gains in quality of life favoring laparoscopy at the 6-week postsurgical period were no longer significant at 6 months.[14,15] Questions remain regarding the efficacy of TLH compared with TAH for endometrial cancer [16] and are awaiting the reports of disease-free survival and overall survival (OS) from these phase III studies.

The completed GOG-LAP2 trial included 2,616 patients with clinical stage I to IIA disease and randomly assigned them two-to-one to comprehensive surgical staging via laparoscopy or laparotomy.[17] Time to recurrence was the primary endpoint, with noninferiority defined as a difference in recurrence rate of less than 5.3% between the two groups at 3 years. The recurrence rate at 3 years was 10.24% for patients in the laparotomy arm, compared with 11.39% for patients in the laparoscopy arm, with an estimated difference between groups of 1.14% (90% lower bound, -1.278; 95% upper bound, 3.996). Although this difference was lower than the prespecified limit, the statistical requirements for noninferiority were not met because of a lower-than-expected number of recurrences in both groups. The OS at 5 years was 89.8% in both groups. Future analyses may determine whether there are subgroups of patients for whom there is a clinically significant decrement when laparoscopic staging is utilized.[17][Level of evidence: 1iiDiii]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I endometrial carcinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Eltabbakh GH, Piver MS, Hempling RE, et al.: Excellent long-term survival and absence of vaginal recurrences in 332 patients with low-risk stage I endometrial adenocarcinoma treated with hysterectomy and vaginal brachytherapy without formal staging lymph node sampling: report of a prospective trial. Int J Radiat Oncol Biol Phys 38 (2): 373-80, 1997.
  2. Homesley HD, Kadar N, Barrett RJ, et al.: Selective pelvic and periaortic lymphadenectomy does not increase morbidity in surgical staging of endometrial carcinoma. Am J Obstet Gynecol 167 (5): 1225-30, 1992.
  3. Aalders J, Abeler V, Kolstad P, et al.: Postoperative external irradiation and prognostic parameters in stage I endometrial carcinoma: clinical and histopathologic study of 540 patients. Obstet Gynecol 56 (4): 419-27, 1980.
  4. 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 40 (1): 55-65, 1991.
  5. Marchetti DL, Caglar H, Driscoll DL, et al.: Pelvic radiation in stage I endometrial adenocarcinoma with high-risk attributes. Gynecol Oncol 37 (1): 51-4, 1990.
  6. Creutzberg CL, van Putten WL, Koper PC, et al.: Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Post Operative Radiation Therapy in Endometrial Carcinoma. Lancet 355 (9213): 1404-11, 2000.
  7. Keys HM, Roberts JA, Brunetto VL, et al.: A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 92 (3): 744-51, 2004.
  8. Scholten AN, van Putten WL, Beerman H, et al.: Postoperative radiotherapy for Stage 1 endometrial carcinoma: long-term outcome of the randomized PORTEC trial with central pathology review. Int J Radiat Oncol Biol Phys 63 (3): 834-8, 2005.
  9. Greven KM, Lanciano RM, Herbert SH, et al.: Analysis of complications in patients with endometrial carcinoma receiving adjuvant irradiation. Int J Radiat Oncol Biol Phys 21 (4): 919-23, 1991.
  10. Stokes S, Bedwinek J, Kao MS, et al.: Treatment of stage I adenocarcinoma of the endometrium by hysterectomy and adjuvant irradiation: a retrospective analysis of 304 patients. Int J Radiat Oncol Biol Phys 12 (3): 339-44, 1986.
  11. Grigsby PW, Kuske RR, Perez CA, et al.: Medically inoperable stage I adenocarcinoma of the endometrium treated with radiotherapy alone. Int J Radiat Oncol Biol Phys 13 (4): 483-8, 1987.
  12. Janda M, Gebski V, Brand A, et al.: Quality of life after total laparoscopic hysterectomy versus total abdominal hysterectomy for stage I endometrial cancer (LACE): a randomised trial. Lancet Oncol 11 (8): 772-80, 2010.
  13. Walker JL, Piedmonte MR, Spirtos NM, et al.: Laparoscopy compared with laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group Study LAP2. J Clin Oncol 27 (32): 5331-6, 2009.
  14. Mourits MJ, Bijen CB, Arts HJ, et al.: Safety of laparoscopy versus laparotomy in early-stage endometrial cancer: a randomised trial. Lancet Oncol 11 (8): 763-71, 2010.
  15. Kornblith AB, Huang HQ, Walker JL, et al.: Quality of life of patients with endometrial cancer undergoing laparoscopic international federation of gynecology and obstetrics staging compared with laparotomy: a Gynecologic Oncology Group study. J Clin Oncol 27 (32): 5337-42, 2009.
  16. Vergote I, Amant F, Neven P: Is it safe to treat endometrial carcinoma endoscopically? J Clin Oncol 27 (32): 5305-7, 2009.
  17. Walker JL, Piedmonte MR, Spirtos NM, et al.: Recurrence and survival after random assignment to laparoscopy versus laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group LAP2 Study. J Clin Oncol 30 (7): 695-700, 2012.
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