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Obstetrics & Gynecology 2001;97:707-711
© 2001 by The American College of Obstetricians and Gynecologists
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ORIGINAL RESEARCH

Vaginal Hysterectomy as Primary Treatment of Endometrial Cancer in Medically Compromised Women

JOHN K. CHAN, MD, YVONNE G. LIN, MS, BRADLEY J. MONK, MD, KRISHNANSU TEWARI, MD, JEFFREY D. BLOSS, MD and MICHAEL L. BERMAN, MD

From the Division of Gynecologic Oncology, The Chao Family Comprehensive Cancer Center, University of California, Irvine—Medical Center, Orange, California.

Address reprint requests to: Michael L. Berman, MD The Division of Gynecologic Oncology The Chao Family Comprehensive Cancer Center University of California, Irvine—Medical Center 101 The City Drive Orange, CA 92868 E-mail: mberman{at}uci.edu


   Abstract
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Abstract
Materials and Methods
 Results
 Discussion
 References
 
Objective: To study the survival, rates and patterns of recurrence, and perioperative morbidity in medically compromised women with endometrial cancer treated by primary vaginal hysterectomy.

Methods: Fifty-one patients with endometrial cancer treated initially by vaginal hysterectomy between 1977 and 1999 were identified at the University of California, Irvine Medical Center and affiliated hospitals. Data were retrieved from hospital and office records. Statistical analysis, including Kaplan-Meier methods, was performed and the disease-specific survival rates were estimated. This study has 80% power to demonstrate a greater than 20% improvement in 5-year survival over historical controls.

Results: Fifty-one women with uterine carcinoma clinically confined to the uterus underwent primary vaginal hysterectomy with (n = 26) or without (n = 25) salpingo-oophorectomy. Eighty-four percent were obese with a body mass index greater than 27. Additional risk factors for surgical complications included hypertension (57%), diabetes mellitus (27%), and cardiovascular disease (18%). One-third of patients had three or more risk factors. Surgical morbidity included one episode of acute hemorrhage necessitating transfusion and abdominal exploration. Blood transfusions were given to four additional patients. There were no perioperative deaths. Five women recurred and expired at a median of 13 months (range 3–53 months) after surgery. The 3- and 5-year disease-specific survival rates were 91.4% and 88.0%, respectively.

Conclusion: Vaginal hysterectomy for the initial treatment of early-stage endometrial cancer is associated with a high rate of cure and minimal morbidity. Thus, it may be considered a reasonable alternative to the abdominal approach in medically compromised women.

For many years, total abdominal hysterectomy and bilateral salpingo-oophorectomy with or without perioperative radiotherapy constituted the standard therapy for women with early-stage uterine carcinoma.1,2 In 1988, the International Federation of Gynaecology and Obstetrics implemented a surgical staging scheme for this disease, which added pelvic and para-aortic lymph node sampling or lymphadenectomy and pelvic washing for cytologic analysis as staging criteria.3–5 Many physicians choose postoperative radiotherapy for selected patients based on their risks of pelvic recurrence.

Most women with endometrial cancer tolerate major abdominal surgery with minimal risk of serious morbidity and mortality; however, some have comorbid conditions including diabetes mellitus, hypertension, obesity, and pulmonary and cardiovascular conditions that can increase their risk for intraoperative and postoperative complications from abdominal surgery. Some of these conditions including diabetes mellitus, hypertension, and obesity are disproportionately associated with uterine cancer compared with other types of pelvic malignancies.1,6,7 Consequently, primary radiotherapy and vaginal hysterectomy are two approaches that have been suggested as alternatives to abdominal surgery for these medically compromised women because of reduced morbidity.8–10 The purpose of this study is to report our experience with 51 such women with early endometrial cancer, based on their clinical assessment, who were treated by primary vaginal hysterectomy.


   Materials and Methods
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Abstract
 Materials and Methods
Results
 Discussion
 References
 
Between January 1977 and December 1999, 976 women were treated for endometrial cancer by physician members of the Division of Gynecologic Oncology at the University of California, Irvine. Of this group of women, 51 were considered poor candidates for abdominal surgery because of various medical conditions and underwent a vaginal hysterectomy. Patients were identified from the tumor registries and surgical logs at the University of California, Irvine—Medical Center, Orange, California, Long Beach Memorial Medical Center, Long Beach, California, and The City of Hope National Medical Center, Duarte, California. Pathologic, surgical, and clinical follow-up data were retrieved from hospital records and office files for all patients. Data were described using univariate statistics (means, medians, proportions). The survivor function was estimated using Kaplan-Meier methods. Disease-specific survival rates at 3 and 5 years are reported. Data from women who died of causes unrelated to endometrial cancer were censored at the time of death. Survival rates for treatment with radiotherapy in medically inoperable patients range from 60% to 70%. With a sample size of 51 patients, this study has greater than 80% power to show a significant improvement in survival above historical controls from 60% to 68%, using a one-sided log-rank test.


   Results
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Abstract
 Materials and Methods
 Results
Discussion
 References
 
Fifty-one women with a median age of 63 years (30–90 years) underwent a vaginal hysterectomy with (n = 26) or without (n = 25) bilateral salpingo-oophorectomy as the primary treatment for endometrial cancer clinically confined to the uterine corpus. Demographic and clinical features of the patients are recorded in Table 1Go. Although marked obesity was the most common reason for choosing vaginal surgery in these patients, the majority also had other medical conditions, which added to the risk of abdominal surgery (Table 2Go). Forty-three (84%) of 51 women were obese with a body mass index greater than 27 kg/m2, and 31 (61%) had a body mass index greater than 35 kg/m2.


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  		Table 1. Demographic and Clinical Features
 

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  		Table 2. Surgical Risk Factors
 
Five patients underwent a unilateral Schuchardt’s incision to enhance exposure of the surgical field. It was necessary to morcellate the uterus in three patients to permit its removal; all of these patients weighed over 250 pounds and had multiple risk factors for serious morbidity of abdominal surgery. Twenty-five (49%) patients underwent either a unilateral (four) or bilateral (21) salpingo-oophorectomy. In the remaining cases, every effort was made to visualize or palpate the ovaries that could not be removed safely. The median operating time was 95 minutes (45–240) with a median estimated blood loss of 250 mL (50–1000 mL). One patient underwent an exploratory laparotomy for postoperative hemorrhage, and five patients required one or two blood transfusions. The median postoperative stay was 4 days (range 2–11) with five patients (10%) requiring a hospital stay of 7–11 days. There were no perioperative deaths.

The most common tumor cell type was endometrioid (90%), but four papillary serous (8%) and one clear cell (2%) carcinoma were included. Histologic grade 1, 2, and 3 were found in 23 (45%), 20 (39%), and 8 (16%) patients, respectively. Ten (20%) patients had no myometrial invasion, whereas 28 (55%) had inner half and 13 (25%) had outer half invasion.

At least 3 years of follow-up were available for 32 (63%) patients in our study population of whom 31 remained disease-free and one died of disease 53 months after surgery. Of the remaining 19 (37%) patients, four died of endometrial cancer at intervals of 3, 7, 13, and 29 months. Six women died of other underlying medical causes, and nine were lost to follow-up without evidence of disease at last contact. Thus, a total of five (10%) women died from their endometrial cancer with a median survival of 13 months.

Eighteen (35%) patients received adjuvant radiotherapy typically for deep myometrial invasion, unfavorable cell types, and high-grade lesions. There were no acute or long-term rectal or bladder complications related to radiotherapy. Patients with grade 1, 2, and 3 disease had 3-year survival rates of 88.2% (95% confidence interval [CI] 72.7–100), 82.9% (95% CI 65.2–100), and 33.3% (95% CI 0–68.6), respectively. All five women who died of recurrent uterine cancer had grade 3 histologies and deep myometrial invasion arising in two adenocarcinomas, one clear cell cancer, and two papillary serous cancers. A summary of their treatment is shown in Table 3Go. Based on the Kaplan-Meier method, the 3- and 5-year disease-specific survival rates were 91.4% (95% CI 83.3–99.5) and 88% (95% CI 77.8–98.2), respectively (Figure 1Go). The lower bound of the 95% confidence limits for the 5-year survival rate in this sample, 77.8%, is higher than observed among historical controls of patients treated by primary radiotherapy alone (60–70%).


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  		Table 3. Cancer-Related Deaths
 


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  		Figure 1. Kaplan-Meier disease-specific survival curve.

 

   Discussion
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Abstract
 Materials and Methods
 Results
 Discussion
References
 
Endometrial carcinoma typically occurs in elderly women who frequently have comorbid conditions including diabetes mellitus, hypertension, coronary artery disease, and obesity all of which can adversely impact surgical outcome.1,11–13 Even though total abdominal hysterectomy with lymphadenectomy or lymph node sampling remains the standard surgical approach for most women with endometrial cancers, alternatives such as vaginal hysterectomy, primary radiotherapy, and hormonal therapy have been reported. Unfortunately, the failure rate for nonsurgical approaches is high. On the other hand, although the failure rate for women managed by vaginal hysterectomy may be somewhat higher than for those who undergo an abdominal hysterectomy with staging, it is appreciably less than that reported for the various nonsurgical approaches. Various radiotherapeutic techniques have been employed including external beam therapy and intracavitary radium application. Most of these reports showed an average 5-year disease-free survival rate of 70%.14–19 There was a recent report of primary radiation therapy for early endometrial cancer that showed disease-free survival rates of 87–95%. However, this study was limited by small sample sizes with uterine recurrence rates up to 14%.20 Lastly, hormone therapy for early endometrial cancer as the primary treatment remains unproved.21 A recent case series and review of literature by Kim et al showed that premenopausal women who desired to preserve their fertility may be treated with progestin therapy with initial response rates of 62%.22 Large series of women treated in this manner with curative intent have not been reported.

Vaginal hysterectomy has been employed as a preferred approach for endometrial cancer treatment in some centers in Europe. Massi et al recently reported a multicenter retrospective analysis comparing vaginal hysterectomy to the abdominal approach in early-stage endometrial cancer patients.23,24 The authors showed that vaginal hysterectomy resulted in 5- and 10-year survival rates of 90% and 87%, respectively, in a population consisting of both good and poor candidates for abdominal surgery.

Similar to the European experience, vaginal hysterectomy has been reported to be an effective mode of surgical management in the United States. Pratt et al reported a retrospective analysis of 100 women who underwent a vaginal hysterectomy for endometrial cancer, 23 of whom had minor treatment-related postoperative complications with no mortalities.10 Sixty-three percent of patients in this study received either preoperative or postoperative radiotherapy, and the adjusted 5-year survival rate was 89.3%. Likewise, Peters et al published the combined experience of 60 patients from two institutions with a reported 5-year survival rate of 91.1% with low morbidity and no mortality.25,26 The survival statistics of past studies from Europe and the United States are similar to those reported in the present study.

Morbid obesity can complicate abdominal surgery with a high risk of wound infection, atelectasis, pneumonia, and sources of febrile morbidity that often result in prolonged hospitalization.27 When an open wound requires prolonged care, the ability to administer timely radiotherapy, when indicated, can be compromised. In contrast to the abdominal approach, vaginal hysterectomy rarely causes such postoperative complications and appears to minimize the risk of cardiovascular complications as well.28 Although morbid obesity was the predominant reason for choosing vaginal surgery in this series, most patients also had other medical problems that added to the risks of abdominal surgery including diabetes mellitus, hypertension, and coronary artery disease. Despite this patient profile, complications typically seen with such patients undergoing abdominal surgery were avoided in this group of women.

Despite the potential advantages of the vaginal approach, vaginal hysterectomy for endometrial cancer precludes the surgeon from assessing the upper abdomen and from performing lymph node resections. Furthermore, it may even be difficult to perform an oophorectomy, especially in nulliparous, morbidly obese patients. Nevertheless, the survival advantage from lymph node resection in endometrial cancer is modest at best, as the majority of endometrial cancer patients do not have occult spread and achieve high cure rates even in the absence of surgical staging. Indeed, some studies have failed to demonstrate a survival benefit of adding pelvic and para-aortic lymphadenectomy to an abdominal hysterectomy whereas others have shown a significant survival advantage.29–31 Understandably, the patient profile will have some impact on this issue. For example, patients with unfavorable histology are more likely to benefit from surgical staging than those with favorable histology. It is noteworthy, therefore, that when obesity complicates uterine cancer, the prognosis typically is good, suggesting that the vaginal approach is particularly suited for the obese patient who has an excellent chance of cure with any approach that includes a hysterectomy. Stage Ia and Ib disease account for up to 60% of patients with endometrial cancer for whom the prevalence of lymph node metastases is low. Women with conditions associated with high-circulating estrogen levels, including hormone replacement therapy or obesity, typically present with stage Ia or Ib disease. Accordingly, the benefits of therapeutic lymphadenectomy in this low-risk population remain to be proved. As suggested by the data of Trimble et al, lymph node excision for staging purposes may not provide any survival benefit in patients with stage I, grade 1 or 2 disease.32

In our series, all patients with grade 1 or 2 disease were cured. Clearly, this outcome could not be improved upon with pelvic and/or para-aortic lymphadenectomy. On the other hand, the eight patients with grade 3 disease including four papillary serous and one clear cell cancer, all with deep myometrial invasion, had poor prognoses with only two patients alive at 5 years. Nevertheless, this subset of patients is at high risk to fail any approach to therapy and might have fared no better if managed by the abdominal route. We strongly advocate surgical staging for the routine treatment of endometrial cancer and believe this is best accomplished by a gynecologic oncologist. However, in our small series comprised of obese and medically compromised women, vaginal hysterectomy appears to be a safe alternative to abdominal surgery or other nonsurgical approaches.


   Footnotes
 
The authors gratefully acknowledge Dr. Richard Buller for his invaluable assistance and guidance. They would like to thank Dr. Kathryn Osann and Dr. Christine McLaren for their assistance with the statistical analysis.

PII S0029-7844(01)01323-0

Received September 25, 2000. Received in revised form January 2, 2001. Accepted January 12, 2001.


   References
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2. Berman ML, Lagasse LD, Watring WG. Prognosis and treatment of endometrial cancer. Am J Obstet Gynecol 1980;136:679–88.[Medline]

3. Shepherd JH. Revised FIGO staging for gynecologic cancer. Br J Obstet Gynaecol 1989;96:889–92.[Medline]

4. Lewis GC, Bundy B. Surgery for endometrial cancer. Cancer 1981;48:568–74.[Medline]

5. Cassia LS, Weppelmann B, Shingleton H, Soong SS, Hatch K, Salter MM. Management of early endometrial carcinoma. Gynecol Oncol 1989;35:362–6.[Medline]

6. Davies A, Magos AL. Indications and alternatives to hysterectomy. Baillieres Clin Obstet Gynaecol 1997;11:61–75.[Medline]

7. Sherman MS, Brinton LA, Potischman N, Kurman RJ, Berman ML, Mortel R, et al. Risk factors and hormone levels in patients with serous and endometrioid uterine carcinomas. Mod Pathol 1997;10: 963–8.[Medline]

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10. Pratt JH, Symmonds RE, Welch JS. Vaginal hysterectomy for carcinoma of the fundus. Am J Obstet Gynecol 1964;88:1063–71.[Medline]

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15. Abayomi O, Tak W, Emami B, Anderson B. Treatment of endometrial carcinoma with radiation therapy alone. Cancer 1982;49: 2466–9.[Medline]

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