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

Dr. Grigsby has done a masterful job of summarizing current information on the use of radiation in the management of patients with endometrial carcinoma. In the summary, he offers clear recommendations as to the appropriate management of various subsets of patients-recommendations that are based, at least to some extent, on the data reviewed. Such decision-making based on often incomplete information is necessary in the absence of appropriately designed randomized trials addressing the specific clinical situation. It is important, however, to understand clearly what we actually know and what we deduce from bits and pieces of data.

Scant Data to Guide Clinical Decisions

What, then, do we actually know? The answer to this question must be based on the results of well-conducted studies that define the clinical classification of patients and properly designed phase III trials of treatment options. The Gynecologic Oncology Group (GOG) conducted the surgical staging study that established the patient classifications presented by Dr. Grigsby in the initial part of his article.[1] Fortunately, the majority of patients fit into the low-risk subgroup (stage IA, grade 1/2) and require only surgery for a high probability of cure. The focus of most efforts to assess the role of radiation therapy has been on the intermediate-risk (stage IA, grade 3; stage IB-II, all grades) and high-risk (stage III/IVA) subgroups.

Unfortunately, within the intermediate- and high-risk subgroups, only three phase III trials have been completed and published at this point, and at least two of these trials are still in follow-up for overall survival. One trial, an Italian study in patients with stage IC-IIIC disease, includes such a heterogeneous population that it is difficult to interpret.[2] No statistically significant differences in failure rates were observed, and progression-free and overall survivals have not been reported.

The second of these trials, GOG-99, evaluated pelvic radiation vs no radiation in patients with surgical stage IA, grade 3, and stage IB-II disease.[3] The initial reports show a statistically significant reduction in failures at a median follow-up of 56 months and survivals of 94% for those receiving radiation vs 89% for the others (P = .09). This study will require further follow-up before a final analysis of overall survival can be performed.

The third study, a Dutch trial, randomized patients with stage IA, grade 3; IB, grade 2/3; or IC, grade 1/2 disease to either pelvic radiation or no radiation after surgical resection.[4] This trial again showed a reduction in pelvic failures, with insufficient events as yet to permit an analysis of overall survival. In each of these studies, radiotherapy consisted of external pelvic irradiation. Data on the use of vaginal brachytherapy or whole-abdomen irradiation come from uncontrolled trials.

Conclusions

In terms of decisions based on what we actually know, therefore, external pelvic irradiation will reduce the incidence of local failures in the intermediate-risk group. This improvement will exact a cost in greater toxicity associated with the radiation. Although external pelvic irradiation may also improve survival, as suggested by the early returns from GOG-99, a final conclusion must await further follow-up. No definitive conclusions can be reached regarding the value of vaginal brachytherapy in addition to external pelvic irradiation, the merits of whole-abdomen irradiation, or, for that matter, the correct management of patients with stage III/IVA disease.

Does this mean that the recommendations made by Dr. Grigsby regarding the use of vaginal brachytherapy or whole-abdomen irradiation are wrong? No. These recommendations represent his best judgment based on uncontrolled trials in specific clinical situations. They should not, however, be confused with decisions based on actual results of phase III trials, and opinions that differ should not be regarded as necessarily wrong. We should have more answers regarding these other issues when the many ongoing phase III trials discussed by Dr. Grigsby finish accrual and mature.

Dr. Grigsby is to be congratulated for an excellent review of the literature and a clear statement of his current practice and its rationale based on that literature.

References:

1. Creasman WT, Morrow CP, Bundy BN: Surgical pathologic spread patterns ofendometrial cancer. Cancer 60:2035, 1987.

2. 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). Gynecol Oncol 68:135, 1998.

3. Maggi R, Cagnazzo G, Atlante G, et al: Risk groups and adjuvant therapy insurgically staged endometrial cancer patients. A randomized multicentre studycomparing chemotherapy with radiation therapy, in: Pecorelli S, Atlante G,Panici PB, Mancuso S (eds): Seventh Biennial Meeting of the InternationalGynecologic Cancer Society, pp 87-101. Rome, Monduzzi Editore, 1999.

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