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Obstetrics & Gynecology 1999;93:599-602
© 1999 by The American College of Obstetricians and Gynecologists
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ORIGINAL RESEARCH

External Pelvic Radiation Therapy in Stage IC Endometrial Carcinoma

MITCHELL F. WEISS, MD, PHILIP P. CONNELL, MD, STEVEN WAGGONER, MD, JACOB ROTMENSCH, MD and ARNO J. MUNDT, MD

From the Section of Gynecologic Oncology, Department of Radiation and Cellular Oncology, and Department of Obstetrics and Gynecology, University of Chicago Hospitals, Chicago, Illinois.

Address reprint requests to: Arno J. Mundt, MD, Department of Radiation and Cellular Oncology, University of Chicago Hospitals, MC 9006, 5758 South Maryland Avenue, Chicago, IL 60637, E-mail: mundt{at}rover.uchicago.edu


   Abstract
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Abstract
Materials and Methods
 Results
 Discussion
 References
 
Objective: To evaluate outcomes of patients with stage IC endometrial carcinoma treated with external whole pelvic radiation but not vaginal brachytherapy.

Methods: Sixty-one women with stage IC endometrial carcinoma had postoperative pelvic radiation without vaginal brachytherapy. The median age was 69 years (range 44–87 years). Most subjects had histologic findings of adenocarcinoma (71%) and grade 2 or 3 disease (74%). The median pelvic irradiation dose was 48.6 Gy (range 43.2–50.4 Gy). No patients received adjuvant chemotherapy or hormonal therapy. The median follow-up time was 69.5 months (range 7–196 months).

Results: The 5-year actuarial disease-free and overall survivals of the entire group were 86.7% and 97.6%, respectively. No patient developed local (vaginal) recurrence. One patient had recurrent disease in the lateral pelvis. Ten patients (16.4%) had distant (extrapelvic) metastases. No serious sequelae were noted, including vaginal necrosis, small bowel obstruction, proctitis, or fistulae.

Conclusion: Local control was excellent in stage IC endometrial carcinoma treated with adjuvant radiation therapy alone. Attention needs to be focused on efforts to control extrapelvic recurrence in patients with this disease.

Most patients with endometrial carcinoma present in stage I, and the mainstay of their treatment is surgery. However, those who have deep myometrial invasion without extrauterine disease (stage IC) are believed to be at risk of recurrence and often receive postoperative radiation therapy, which typically consists of a combination of external beam whole pelvic irradiation and vaginal brachytherapy. It remains unclear, however, whether both types of radiation are necessary. Pelvic radiation alone might be capable of sterilizing potential residual microscopic disease in the regional lymph nodes, obviating the need for brachytherapy. Although many investigators reported the outcomes of patients with stage I disease treated with surgery and adjuvant radiotherapy,1–10 few focused on the outcomes of patients treated with postoperative pelvic radiation alone.11–14 Most published reports included patients without deep myometrial invasion and at low risk for local (vaginal) recurrence.15

At the University of Chicago, women with stage IC endometrial cancer are treated routinely with postoperative radiation. In the past, patients received pelvic radiation and vaginal brachytherapy, but more recently, vaginal brachytherapy has been omitted. The purpose of this study was to evaluate outcomes of patients treated without vaginal brachytherapy.


   Materials and Methods
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Abstract
 Materials and Methods
Results
 Discussion
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In 61 women, stage IC endometrial carcinoma was diagnosed and treated with adjuvant pelvic radiation alone in the Department of Radiation and Cellular Oncology, following surgery, at the University of Chicago between June 1986 and June 1995. Carcinomas diagnosed before 1988 were restaged according to the 1988 International Federation of Gynecology and Obstetrics (FIGO) criteria. Patient and tumor characteristics of the entire group are summarized in Table 1Go. Median subject age was 69 years (range 44–87 years). The most common histologic finding was adenocarcinoma (71%). Radiographic studies included chest x-rays (100%) and abdominopelvic computed tomography (34%).


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  		Table 1. Tumor Characteristics in 61 Patients
 
Surgery consisted of total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) abdominopelvic exploration, and peritoneal washings. Pelvic and paraaortic lymph node samplings were done in 50.8% and 44.3% of patients, respectively. All patients received postoperative pelvic radiation 4–6 weeks after TAH-BSO. The median radiation dose was 48.6 Gy (range 43.2–50.4 Gy). Treatment was delivered with 6–24-MV photons by a four-field technique using daily fractionations of 1.8 to 2 Gy. No patients received vaginal brachytherapy or adjuvant chemotherapy.

Local recurrence was defined as disease recurrence in the central pelvis, including the upper vagina. Any disease within the pelvic field was defined as a pelvic recurrence. Actuarial analyses of local recurrence, pelvic recurrence, disease-free survival, and cause-specific survival were plotted according to the Kaplan-Meier method. All intervals were determined from the date of diagnosis. Median follow-up of patients was 69.5 months (range 7–196 months). Of the surviving patients, 70% had a follow-up examination in the past 12 months.


   Results
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Abstract
 Materials and Methods
 Results
Discussion
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The 5-year actuarial disease-free and cause-specific survivals of the entire group were 86.7% and 97.6%, respectively (Figures 1Go and 2Go). There were no local recurrences. One woman had a nonlocal pelvic recurrence. The 5-year actuarial local and pelvic recurrence rates were 0% and 1.8%, respectively. Ten patients had extrapelvic recurrences, the most common sites of which were lung and distant nodes (mediastinum, paraaortic and supraclavicular regions). Extrapelvic recurrences were not correlated with tumor type, grade, lymph node sampling, or lymphovascular invasion. Grade 2 or 3 tumors had higher incidences of extrapelvic recurrence than grade 1 tumors (11.1% versus 0%). However, the difference did not reach statistical significance (P = .18).



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  		Figure 1. Disease-free survival of entire group.

 


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  		Figure 2. Cause-specific survival of entire group.

 
Short-term sequelae (diarrhea and urinary frequency) were noted by most subjects but were generally mild and well controlled with oral medication. No subject needed a treatment break for these sequelae. Only three women (5%) developed long-term sequelae. Two subjects had mild vaginal stenosis and one noted intermittent loose stools. No women had severe stenosis, vaginal vault necrosis, small bowel obstruction, proctitis, or fistulae.


   Discussion
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Abstract
 Materials and Methods
 Results
 Discussion
References
 
The purpose of this study was to determine the outcomes of patients with stage IC endometrial carcinoma treated with surgery and adjuvant pelvic radiation alone. Our results suggested that, in women treated this way, there is excellent local control of the cancer. None of the 61 patients (74% of whom had grade 2 or 3 tumors) had local recurrence with median follow-up of 69.5 months. Our overall pelvic control rate at 5 years was excellent (98.2%). Few investigators focused on stage I endometrial cancer patients with deep myometrial invasion treated with postoperative pelvic radiation without vaginal brachytherapy. Torrisi et al11 evaluated 46 clinically staged IA–B endometrial cancer patients treated with TAH-BSO and pelvic radiation alone. Twenty-three (50%) had myometrial invasion to the outer third and 17 (37%) had middle-third invasion. Three patients (6.5%) had pelvic recurrences (two in the upper vagina). Since the 1988 FIGO staging system was not used, it is unclear how many patients had stage IC disease.11 In contrast, Rush and coworkers12 noted no local recurrences in 53 patients with stage IC disease after postoperative pelvic radiation alone. Similarly, Piver and Hempling14 treated 41 patients who had either grade 3 disease or more than half myometrial invasion by using postoperative pelvic radiation without vaginal brachytherapy. Thirty-two patients had stage IC disease and local recurrence developed in none. A recurrence developed in one in the lateral pelvis. Randall and coworkers13 evaluated the outcome of 52 patients with stage I disease treated with TAH-BSO and pelvic irradiation alone. Because the 1988 FIGO system was not used, it is unclear how many patients had stage IC disease. Of the 20 patients with invasion to the outer third of the myometrium, only one developed a recurrence in the pelvis. As shown in Table 2Go, there was no increased risk of local recurrence in patients with deep myometrial invasion treated with postoperative pelvic radiation alone compared with those treated with pelvic radiation plus vaginal brachytherapy.


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  		Table 2. Local Recurrence in Stage I Endometrial Cancer With Deep Myometrial Invasion Treated With Pelvic Radiation With or Without Vaginal Brachytherapy
 
Eliminating vaginal brachytherapy in treatment of stage IC disease has many important potential benefits. The risk of radiation sequelae, including vaginal stenosis and vault necrosis, is reduced. None of our patients treated with pelvic radiation alone developed vaginal necrosis, fistulae, or significant stenosis. In a study of 330 patients with stage I or II endometrial cancer treated with surgery, pelvic radiation, and vaginal brachytherapy, Mandell et al16 reported a 3.7% vaginal complication rate (2.7% stenosis, 1% necrosis). In a similar series, Nori and coworkers7 noted vaginal stenosis and necrosis in 2.5% and 0.5% of their patients, respectively. Randall et al13 analyzed the risk of long-term sequelae in patients with stage I endometrial cancer treated with pelvic radiation with and without vaginal brachytherapy. Patients receiving vaginal brachytherapy had higher rates of chronic diarrhea (9.8% versus 3.8%) and rectal bleeding or proctitis (18.6% versus 3.8%) compared with patients treated with pelvic radiation alone.13 Vaginal brachytherapy also has potential short-term sequelae, particularly when delivered with low-dose-rate techniques that require inpatient hospitalization. Lanciano et al17 noted that age over 50 years was independently correlated with the development of short-term sequelae during vaginal brachytherapy for gynecologic tumors. That correlation is particularly relevant because endometrial cancer patients often present in the sixth and seventh decades of life.

Vaginal brachytherapy can also adversely affect sexual function. We did not have sufficient information from our patients to comment on sexual outcomes; however, others performed detailed analyses of sexual outcomes in patients with endometrial carcinoma. Bruner et al18 conducted a prospective study of sexual function in 48 women treated with postoperative vaginal brachytherapy with and without pelvic radiation. After treatment, 44% of patients complained of dyspareunia. In addition, sexual satisfaction was found to be significantly decreased compared with pretreatment baseline. Cochran and coworkers19 noted that more endometrial cancer patients treated with postoperative pelvic radiation and vaginal brachytherapy had decreased coital frequency (44% versus 25%) compared with surgery alone.19 Neither study included patients who received pelvic radiation without vaginal brachytherapy.

Eliminating vaginal brachytherapy also reduces overall treatment time commitment. Low-dose-rate brachytherapy typically requires 1 or 2 days of hospitalization. Many centers now use high-dose-rate techniques, obviating hospitalization and general anesthesia. High-dose-rate brachytherapy is generally performed over several sessions, which adds time to the overall treatment course and has its own potential short-term sequelae.

In today’s cost-containment health care environment, another potential benefit of eliminating vaginal brachytherapy is reduced treatment cost. Konski and coworkers20 did a cost analysis of treatment options for stage I endometrial carcinoma. Adjuvant vaginal brachytherapy added significant costs compared with pelvic radiation alone. The overall costs of low-dose-rate and high-dose-rate vaginal brachytherapy were 1.8 and 2.3 times the cost of pelvic radiation alone.20

Our analysis has several limitations. It is retrospective and suffers from all the limitations inherent in such an analysis. The women were treated over a 15-year period, although they were staged and treated uniformly. Only patients with deep myometrial invasion found in hysterectomy specimens were included, and the median follow-up exceeded 5 years; 74% had grade 2 or 3 disease.


   Footnotes
 
Presented at the 40th Annual Meeting of the American Society for Therapeutic Radiology and Oncology, October 25–29, 1998, Phoenix, Arizona.

PII S0029-7844(98)00479-7

Received July 14, 1998. Received in revised form September 15, 1998. Accepted October 8, 1998.


   References
Top
Abstract
 Materials and Methods
 Results
 Discussion
 References
 
1. Surwit EA, Joelsson I, Einhorn N. Adjunctive radiation therapy in the management of stage I cancer of the endometrium. Obstet Gynecol 1981;58:590–5.[Abstract/Free Full Text]

2. Mayr NA, Wen BC, Benda JA, Sorosky JI, Davis CS, Fuller RW, et al. Postoperative radiation therapy in clinical stage I endometrial cancer: Corpus, cervical, and lower uterine segment involvement-patterns of failure. Radiology 1995;196:323–8.[Abstract/Free Full Text]

3. Eifel PJ, Ross J, Hendrickson M, Cox RS, Kempson R, Martinez A. Adenocarcinoma of the endometrium. Analysis of 256 cases with disease limited to the uterine corpus: Treatment comparisons. Cancer 1983;52:1026–31.[Medline]

4. Sause W, Fuller DB, Smith WG, Johnson GH, Plenk HP, Menlove RB. Analysis of preoperative intracavitary cesium application versus postoperative external beam radiation in stage I endometrial carcinoma. Int J Radiat Oncol Biol Phys 1990;18:1011–7.[Medline]

5. Grigsby PW, Perez CA, Kuten A, Simpson JR, Garcia DM, Camel HM, et al. Clinical stage I endometrial cancer: Results of adjuvant irradiation and patterns of failure. Int J Radiat Oncol Biol Phys 1991;21:379–85.[Medline]

6. Belinson JL, Spirou B, McClure M, Badger G, Pretorius RG, Roland TA. Stage I carcinoma of the endometrium: A 5-year experience utilizing preoperative cesium. Gynecol Oncol 1985;20:325–35.[Medline]

7. Nori D, Hilaris BS, Tome M, Lewis JL, Birnbaum S, Fuks Z. Combined surgery and radiation in endometrial carcinoma: An analysis of prognostic factors. Int J Radiat Oncol Biol Phys 1987; 13:489–97.[Medline]

8. Rosenberg P, Blom R, Hogberg T, Simonsen E. Death rate and recurrence pattern among 841 clinical stage I endometrial cancer patients with special reference to uterine papillary serous carcinoma. Gynecol Oncol 1993;51:311–5.[Medline]

9. Konski A, Domenico D, Tyrkus M, Irving D, Neisler J, Phibbs G, et al. Prognostic characteristics of surgical stage I endometrial adenocarcinoma. Int J Radiat Oncol Biol Phys 1996;35:935–40.[Medline]

10. Carey MS, O’Connell GJ, Johanson CR, Goodyear MD, Murphy KJ, Daya DM, et al. Good outcome associated with a standardized treatment protocol using selective postoperative radiation patients with clinical stage I adenocarcinoma of the endometrium. Gynecol Oncol 1995;57:138–44.[Medline]

11. Torrisi JR, Barnes WA, Popescu G, Whitfield G, Barter J, Lewan-dowski G, et al. Postoperative adjuvant external-beam radiotherapy in surgical stage I endometrial carcinoma. Cancer 1989;64: 1414–7.[Medline]

12. Rush S, Gal D, Potters L, Bosworth J, Lovecchio J. Pelvic control following external beam radiation for surgical stage I endometrial adenocarcinoma. Int J Radiat Oncol Biol Phys 1995;33:851–4.[Medline]

13. Randall ME, Wilder J, Greven K, Raben M. Role of intracavitary cuff boost after adjuvant external irradiation in early endometrial carcinoma. Int J Radiat Oncol Biol Phys 1990;19:49–54.[Medline]

14. Piver MS, Hempling RE. A prospective trial of postoperative vaginal radium/cesium for grade 1–2 less than 50% myometrial invasion and pelvic radiation therapy for grade 3 or deep myometrial invasion in surgical stage I endometrial adenocarcinoma. Cancer 1990;66:1133–8.[Medline]

15. Leibel SA, Wharam MD. Vaginal and paraaortic lymph node metastases in carcinoma of the endometrium. Int J Radiat Oncol Biol Phys 1980;6:893–6.[Medline]

16. Mandell L, Nori D, Anderson L, Hilaris B. Postoperative vaginal radiation in endometrial cancer using a remote afterloading technique. Int J Radiat Oncol Biol Phys 1985;11:473–8.[Medline]

17. Lanciano R, Corn B, Martin E, Schultheiss T, Hogan WM, Rosenblum N. Perioperative morbidity of intracavitary gynecologic brachytherapy. Int J Radiat Oncol Biol Phys 1994;29:969–74.[Medline]

18. Bruner DW, Lanciano R, Keegan M, Corn B, Martin E, Hanks GE. Vaginal stenosis and sexual function following intracavitary radiation for the treatment of cervical and endometrial carcinoma. Int J Radiat Oncol Biol Phys 1993;27:825–30.[Medline]

19. Cochran SD, Hacker NF, Wellisch DK, Berek JS. Sexual functioning after treatment for endometrial cancer. J Psychosocial Oncol 1987; 5:47–54.

20. Konski AA, Bracy PM, Jurs SG, Weiss SJ, Zeidner SR. Cost minimization analysis of various treatment options for surgical stage I endometrial carcinoma. Int J Radiat Oncol Biol Phys 1997;37:367–73.[Medline]




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