Commentary (Thompson): Update on Radiation Therapy for Endometrial Cancer

Dr. Grigsby does an excellent job of summarizing the accepted, stage-by-stage treatment recommendations as well as the controversies surrounding the treatment of endometrial carcinoma. This review is both important and timely, as we have seen the incidence of endometrial cancer increase over the past few years to the point where it is now the most common gynecologic malignancy.

Surgical Staging Controversy

Controversies surround the initial surgical management of endometrial cancer, specifically in regard to the extent of surgical staging recommended. Especially pertinent is Dr. Grigsby’s discussion of the management of apparent early-stage endometrial cancer patients who have not undergone surgical staging.

Although some authors advocate surgical staging with lymph node dissection as the standard of care,[1] some question the necessity and rationale for more aggressive lymph node dissection in a patient population for which the resulting data provide only prognostic information and only indirectly influence survival (via decisions regarding adjuvant therapy).[2] Nonetheless, the current FIGO staging system for endometrial cancer is defined as a surgical staging system rather than a clinical staging system (as it was described before the 1988 revision).[3]

Our practice reflects what Dr. Grigsby describes as the most common treatment approach for endometrial cancer in the United States. That is, most of our patients with apparent early-stage disease are referred postoperatively to be considered for radiation therapy without undergoing complete surgical staging.

Data from a prospective randomized trial of adjuvant postoperative radiation therapy can be used to develop treatment guidelines in this context. The Gynecologic Oncology Group’s GOG-99 trial surgically staged all patients and used only external-beam irradiation without brachytherapy.[4] Given the absence of complete surgical staging data for the majority of our patients, we are often faced with the prospect of making decisions regarding adjuvant treatment without the benefit of guidelines developed from recent trials that use data only from surgically staged patient populations.

Further Guidance

More recently, actuarial data from the Postoperative Radiation Therapy in Endometrial Cancer (PORTEC) trial have provided some guidance.[5] In this study of over 700 patients, who were treated initially with total abdominal hysterectomy/bilateral salpingo-oophorectomy (TAH/BSO), complete surgical staging was not required. Again, patients were randomized to no adjuvant treatment vs pelvic external-beam irradiation without brachytherapy.

Both the PORTEC and GOG-99 trials failed to show any improvement in survival for the radiation therapy group. There appeared to be some difference in locoregional recurrence rates (14% failure in the untreated group vs 4% in the group receiving pelvic irradiation in the PORTEC trial, and 12% pelvic recurrence rate for untreated patents vs 2% pelvic failure rate for irradiated patients in GOG-99). Notably, almost three-fourths of the recurrences developed in the vagina in the PORTEC trial.

A review of the data from these recent trials, when combined with data from previous trials that employed brachytherapy as adjuvant therapy, either with or without external-beam pelvic irradiation,[6] could lead to the development of reasonable treatment guidelines.

Adjuvant Treatment Recommendations

As outlined by Dr. Grigsby, decisions regarding adjuvant treatment can be made using available information on patients, with or without complete surgical staging. Postoperative radiation to the pelvis, even if limited to vaginal cuff brachytherapy (for which there is no evidence of improvement in survival), can significantly increase local control and prevent significant morbidity. Adjuvant external-beam irradiation of the pelvis in patients with low-grade stage IA/B disease can be safely omitted, with a subsequent decrease in expense and treatment-related morbidity in these patients. The recent increase in the availability of high-dose-rate brachytherapy as an outpatient alternative makes adjuvant therapy more convenient and accessible to patients, while avoiding costly hospital stays.

Treatment guidelines for patients with advanced disease, as well as palliative guidelines, are outlined by Dr. Grigsby and can be applied on a case-by-case basis using the algorithms included in his tables.

References:

1. Orr J, Holimon JL, Orr PF, et al: Stage I corpus cancer: Is teletherapynecessary? Am J Obstet Gynecol 176(4):777-789 (incl discussion), 1997.

2. Petereit DG: Syllabus 107 of the annual meeting of the American Society ofTherapeutic Radiation and Oncology, 2000.

3. FIGO: International Federation of Gynecology and Obstetrics:Classification and staging of malignant tumors in the female pelvis: Annualreport on the results of treatment in gynecological cancer. Int J GynaecolObstet 28:189, 1989.

4. Roberts JA, Brunetto VL, Keys HM, et al: A phase III randomized study ofsurgery vs surgery plus adjunctive radiation therapy in intermediate-riskendometrial adenocarcinoma (GOG 99) (abstract). Gynecol Oncol 68:135, 1998.

5. Creutzberg CL, van Putten WL, Koper PC, et al: Surgery and postoperativeradiotherapy vs surgery alone for patients with stage 1 endometrial carcinoma:Multicentre randomised trial. PORTEC Study Group. Post Operative RadiationTherapy in Endometrial Carcinoma. Lancet 355(9213):1404-1411, 2000.

6. Aalders J, Abeler V, Kolstad P, et al: Postoperative external irradiationand prognostic parameters in stage I endometrial carcinoma: Clinical andhistopathologic study of 540 patients. Obstet Gynecol 56(4):419-427, 1980.