OBJECTIVE: To compare intraoperative and postoperative outcomes, pathologic findings, cancer recurrence, and death rates in normal-weight, overweight, obese, and morbidly obese women undergoing radical hysterectomy and pelvic lymphadenectomy for early-stage cervical cancer.
METHODS: A review of patients who underwent radical hysterectomy and pelvic lymphadenectomy for invasive cervical cancer between 1990 and 2006 was performed. On the basis of body mass index (BMI) (calculated as weight [kg]/[height (m)]2), women were categorized as normal weight (BMI 18.5–24.9), overweight (BMI 25.0–29.9), obese (BMI 30.0–34.9), or morbidly obese (BMI at least 35.0).
RESULTS: Four hundred eight women met the inclusion criteria. Of these, 155 (38%) were normal weight, 126 (31%) were overweight, 77 (19%) were obese, and 50 (12%) were morbidly obese. There were no statistically significant differences between these four groups in age, Charlson comorbidity score, smoking history, stage, histologic grade or subtype, tumor size, depth of invasion, transfusion rate, operative time, or intraoperative complications. Higher BMI was significantly correlated with higher estimated operative blood loss (P=.001). There were no statistically significant differences between the groups in pathologic findings, length of postoperative hospital stay, postoperative complications, readmission rate, or proportion of women receiving adjuvant radiotherapy. At a median follow-up time of 64 months, there were no differences between groups in rates of recurrence or death from disease.
CONCLUSION: Radical hysterectomy and pelvic lymphadenectomy is feasible for obese and morbidly obese women with cervical cancer. Obesity alone should not be a contraindication to radical hysterectomy in women with cervical cancer.
LEVEL OF EVIDENCE: II
Radical hysterectomy and pelvic lymphadenectomy is a reasonable treatment option in obese and morbidly obese women with early-stage cervical cancer.
From the Departments of 1Gynecologic Oncology and 2Radiation Oncology, the University of Texas M. D. Anderson Cancer Center, Houston, Texas; the 3Gynecologic Oncology Service, Hospital de Clinicas de Porto Alegre, Universidade Federal Do Rio Grande Do Sul, Ramiro Barcelos, Porto Alegre, Brazil; and the 4Department of Obstetrics, Gynecology, and Reproductive Sciences, the University of Texas Medical School–Memorial Hermann Hospital, Houston, Texas.
See related article on page 835.
Corresponding author: Michael Frumovitz, MD, MPH, Department of Gynecologic Oncology, CPB6.3244, Unit 1362, the University of Texas M. D. Anderson Cancer Center, 1155 Herman Pressler, Houston, TX 77030; e-mail: email@example.com.
Financial Disclosure The authors have no potential conflicts of interest to disclose.
Among women worldwide, cervical cancer is the second most common cause of cancer death and cancer-related years of life lost.1 Most cervical cancer cases and deaths occur in developing nations because, in developed countries, widespread Pap testing and aggressive treatment of preinvasive disease have significantly decreased morbidity and mortality from this malignancy. In the United States, more than half of women with cervical cancer are diagnosed with stage I disease (ie, tumor clinically limited to the cervix), for which the prognosis is excellent.2 Primary treatment with surgery or irradiation alone cures 85–90% of patients with stage I cervical cancer.3–6
Although surgery and radiotherapy have equivalent clinical efficacy, these two treatment modalities are associated with distinct acute and late complications. In long-term survivors with early-stage cervical cancer, overall quality of life and sexual function are better in women treated with surgery compared with those treated with primary radiotherapy.7 For this reason, we typically recommend radical hysterectomy for women with early-stage cervical cancer who are deemed appropriate surgical candidates.
Unfortunately, obese women are often considered poor candidates for radical surgery. Among gynecologic oncologists contemplating radical hysterectomy for obese patients, there seems to be a perception that obesity is associated with increased operative blood loss and an increased rate of postoperative complications, even though prior studies have not shown this to be true.8–11 In addition, many believe that obesity may compromise the “radicality” of the surgical procedure, reducing the amount of vaginal and parametrial tissue removed and the number of pelvic lymph nodes retrieved, thereby potentially compromising overall survival.
The objective of this study was to compare the intraoperative and postoperative outcomes, pathologic findings, and rates of cancer recurrence and death from disease in normal-weight, overweight, obese, and morbidly obese women with early-stage cervical cancer who underwent radical hysterectomy and pelvic lymph node dissection.
MATERIALS AND METHODS
Before initiation, our study was approved by the institutional review board at the University of Texas M. D. Anderson Cancer Center. We reviewed the records of all patients who underwent radical hysterectomy and pelvic lymphadenectomy for cervical cancer at M. D. Anderson Cancer Center from January 1, 1990, through December 31, 2006. We included patients with stages IA1–IB2 primary cervical cancer with squamous, adenocarcinoma, or adenosquamous lesions who underwent radical hysterectomy via laparotomy or laparoscopy. Patients were excluded if they had undergone radical hysterectomy for clinical stage II endometrial cancer, if they underwent surgical exploration for radical hysterectomy but had the procedure aborted because of intraperitoneal disease or nodal involvement, or if their body mass index (BMI) was less than 18.5 (underweight).
Body mass index was computed for each patient by dividing her weight in kilograms by her height in meters squared. Using definitions from the National Institutes of Health, patients then were classified as normal weight (BMI 18.5–24.9), overweight (BMI 25.0–29.9), obese (BMI 30.0–34.9), or morbidly obese (BMI 35.0 or higher). Medical comorbidities were assigned a score in the manner described by Charlson et al (Charlson score).12
Type II or type III abdominal radical hysterectomy was performed for all patients. Which type of radical hysterectomy to perform was at the surgeon's discretion. Pelvic lymphadenectomy typically was performed after completion of the radical hysterectomy. For women who underwent lymphatic mapping, sentinel nodes were removed at the beginning of the case, before radical hysterectomy. Operative blood loss was estimated by the anesthesiologist and recorded accordingly. Typically, the surgeon agreed to this estimate unless he or she felt strongly that the anesthesiologist had grossly overestimated (eg, patients with large amounts of irrigation mixed with blood) or underestimated (eg, patients in whom large amounts of blood were evacuated using towels or laparotomy pads) blood loss.
Because of the large number of surgeons performing open radical hysterectomies at our institution, practice patterns regarding bladder management varied—some patients were sent home with Foley catheters or suprapubic catheters and others were sent home with instructions for intermittent self-catheterization. Most patients were scheduled to return to the clinic approximately 2 weeks after radical hysterectomy for a voiding trial. Adequate voiding usually was defined as a residual urine volume of less than 100 mL. Patients who failed the voiding trial had the catheter replaced or continued intermittent self-catheterization, and follow-up voiding trials were scheduled at the clinician's discretion.
All pathologic specimens were examined by an attending gynecologic pathologist. Before pathologic processing, radical hysterectomy specimens were grossly examined. At the time of gross inspection, the size of the parametrium was measured linearly from its attachment to the cervix. The size of the vaginal cuff obtained was measured in a similar manner.
Mann-Whitney, Kruskal-Wallis, and χ2 tests were used to evaluate differences between groups. Disease-free and overall survival were calculated using the method described by Kaplan and Meier. Missing data were coded as “unknown,” and those data points were excluded from the analysis. Unless otherwise noted, P values were not adjusted for multiple comparisons. P values less than .05 were considered statistically significant. All data were analyzed using SPSS 15.0 for Windows (SPSS, Inc., Chicago, IL).
From 1990–2006, 527 patients with newly diagnosed cervical cancers who were radical hysterectomy candidates based on clinical stage and histology presented to our institution. Of these, 119 (23%) were dispositioned to primary radiation therapy with or without chemotherapy. When analyzed by weight group, 16% of normal-weight women, 21% of overweight women, 22% of obese women, and 40% of morbidly obese women received radiotherapy when their tumor size and physical examination might have made them candidates for primary surgery (P<.001).
The remaining 408 patients met inclusion criteria and are the basis for this study. Of these, 155 (38%) were normal weight (median BMI 22.1, range 18.5 to 24.9), 126 (31%) were overweight (median BMI 27.1, range 25.0 to 29.9), 77 (19%) were obese (median BMI 32.5, range 30.0 to 35.3), and 50 (12%) were morbidly obese (median BMI 38.7, range 35.6 to 61.7). Because of missing data points, the totals for some categories of data presented are less than 408.
Patient demographics are described in Table 1. There were no statistically significant differences between the four groups in age, Charlson score, or smoking history. There were proportionally more white women in the normal-weight and overweight groups and more Hispanic women in the obese and morbidly obese groups (P<.001). Preoperative tumor factors are described in Table 2. There were no statistically significant differences between the four groups with regard to clinical stage, histologic grade or subtype, tumor size, or depth of invasion. The median time from date of diagnosis to surgery was 15 days for normal-weight women, 16 days for overweight women, 16 days for obese women, and 18 days for morbidly obese women (P=.81). There were no statistically significant differences between the groups with regard to surgical approach (open compared with laparoscopic), type of radical hysterectomy performed (II compared with III), operative time, or intraoperative complications (Table 3). As patients' BMI increased, surgeons were more likely to employ a vertical skin incision rather than a transverse skin incision (Pfannenstiel-, Maylard-, or Cherney-type incisions) (P<.001). Higher BMI was significantly correlated with higher estimated operative blood loss (P=.001); however, transfusion rates were similar for the four groups.
On pathologic examination, there were no statistically significant differences between the groups in number of lymph nodes resected, length of parametrium or vaginal cuff obtained, rate of achievement of negative margins, or rate of nodal metastasis (Table 4). Postoperatively, there were no statistically significant differences between the groups with regard to length of postoperative hospital stay, postoperative infectious or noninfectious complications, readmission rate, or proportion of women receiving adjuvant radiotherapy (Table 5). The median time to return of voiding function was 20 days for normal-weight women compared with 15 days for overweight women, 13 days for obese women, and 14 days for morbidly obese women (P<.001). Because of the low number of complications, a separate analysis was performed after combining the patients into two groups (normal weight and overweight [n=281] compared with obese and morbidly obese [n=127]). There were no significant differences compared with the above-noted results when the analysis was performed in this manner.
At a median follow-up time of 64.1 months, there was no statistically significant difference between the groups in recurrence rate (9.7% for normal-weight women, 8.7% for overweight women, 5.2% for obese women, and 6% for morbidly obese women) or death from disease (7.1% for normal-weight women, 7.1% for overweight women, 3.9% for obese women, and 2.0% for morbidly obese women). Median overall and disease-free survival had not yet been reached at the time of this analysis.
Our findings indicate that radical hysterectomy with pelvic lymphadenectomy in overweight, obese, and morbidly obese women with early-stage cervical cancer is feasible. Radical hysterectomy and pelvic lymphadenectomy in these groups resulted in intraoperative and postoperative complication rates similar to those in women with normal BMIs. In addition, surgeons were able to obtain equivalent pathologic specimens, including length of parametria and vaginal cuff, rate of negative margins, and number of pelvic lymph nodes resected, in overweight, obese, and morbidly obese women as in normal-weight women. Finally, recurrence rate and death from disease in overweight, obese, and morbidly obese patients were similar to those in normal-weight patients.
Our findings apply to women who are considered appropriate surgical candidates, which explain the similar Charlson comorbidity scores for each of the four weight groups. Obesity is not part of the Charlson scoring system, and, therefore, BMI alone did not affect the score. However, presumably the morbidly obese patients had other comorbid factors such as hypertension, heart disease, or diabetes that would increase their Charlson score. Because the morbidly obese patients with multiple comorbid conditions were poor surgical candidates, these women likely were triaged to primary radiotherapy. For those morbidly obese women without significant medical comorbidities, these data support the ability of gynecologic oncologists to adequately perform radical surgery.
Calle et al13 report that increased BMI is strongly associated with increased death rates from all cancers. In their study, compared with normal-weight patients with cervical cancer, overweight women had a relative risk of cervical cancer–related mortality of 1.38, obese women had a relative risk of 1.23, and morbidly obese women had a relative risk of 3.20.13 However, the study is limited because patients with all stages of cervical cancer were analyzed together. We could find no published data regarding the correlation, if any, between obesity and stage at diagnosis of cervical cancer. However, poor access to health care and low socioeconomic status are strongly associated with obesity.14 In addition, obese women are less likely to undergo cervical cancer screening.15 One might hypothesize, therefore, that obese women, with their poor access to health care, low socioeconomic status, and decreased rate of cervical cancer screening, would be more likely to have advanced disease at diagnosis of cervical cancer and an associated poorer overall prognosis.
Our findings are similar to those of other published studies examining radical hysterectomy in obese women with early-stage cervical cancer. Levrant et al10 found similar intraoperative, postoperative, and long-term complication rates and equal 5-year survival rates for normal-weight and obese women with cervical cancer treated with radical hysterectomy. Finan et al9 confirmed these findings in their review of similar patients. Interestingly, they found that underweight patients (BMI less than 20) had poorer survival than normal-weight and obese patients. Cohn et al8 also found that radical hysterectomy in obese women was feasible and safe, associated with minimal morbidity and excellent survival. These previous studies, however, used older definitions of obesity, such as 20% greater than ideal body weight.10 In addition, some of these previous studies combined all patients with BMIs greater than 30 into a single “obese” group and either compared them with “normal-weight” patients (BMI 20–30)9 or did not use a comparison group at all.8 None of these previous studies evaluated outcomes from radical hysterectomy using the modern National Institutes of Health definitions of normal weight, overweight, obese, and morbidly obese.
Our overall transfusion rate of 38% is lower than transfusion rates reported in other publications, which ranged from 49% to 81%.16–21 However, the overall transfusion rate in this study is higher than the transfusion rate of 15% that we reported for abdominal radical hysterectomy in 54 women with early-stage cervical cancer who underwent surgery in 2004–2006.22 An additional analysis of the data presented here indicates that our transfusion rate for all patients (regardless of BMI) was 46% before 2001, compared with only 22% from 2001 to 2006 (P<.001). One factor that may explain the recent decrease in blood loss may be the application of new technologies to open surgeries. We have adapted many of the instruments developed for laparoscopy, such as the Harmonic ACE (Ethicon Endo-Surgery, Inc., Cincinnati, OH) and the LigaSure (Covidien, Mansfield, MA), to surgeries performed via laparotomy and as a result are experiencing less blood loss and faster operating times for vulvar, cervical, uterine, and ovarian cancers. We previously published our experience in applying these technologies to pelvic exenterative procedures and similarly found less blood loss, fewer transfusions, and decreased length of hospital stay.23
Multiple authors have found that radical surgery provides improved quality of life and improved sexual function compared with radiotherapy as treatment for early-stage cervical cancer.7,24,25 These studies compared surgery via laparotomy with radiotherapy. However, radical surgery via minimally invasive approaches is also becoming more feasible for obese patients. In our previous report on laparoscopic radical hysterectomy, we showed that the minimally invasive approach to early-stage cervical cancer is safe and reasonable regardless of BMI, including for morbidly obese women.22 We believe that performing radical hysterectomy via laparoscopy as opposed to laparotomy will further improve quality of life, and we are currently conducting studies to test this hypothesis.
Although there were no differences in age or Charlson comorbidity score between the four BMI groups in this study, selection bias certainly may have affected our findings. In particular, elderly obese women with multiple comorbidities may not have been considered appropriate surgical candidates and therefore may have been treated with radiotherapy instead. However, our data strongly support consideration of radical hysterectomy and pelvic lymphadenectomy as definitive treatment for early-stage cervical cancer in morbidly obese women with minimal medical comorbidities. Obesity alone should not be considered a contraindication to radical hysterectomy and lymphadenectomy.
1. Waggoner SE. Cervical cancer. Lancet 2003;361:2217–25.
2. Lu KH, Burke TW. Early cervical cancer. Curr Treat Options Oncol 2000;1:147–55.
3. Eifel PJ, Burke TW, Delclos L, Wharton JT, Oswald MJ. Early stage I adenocarcinoma of the uterine cervix: treatment results in patients with tumors less than or equal to 4 cm in diameter. Gynecol Oncol 1991;41:199–205.
4. Hopkins MP, Morley GW. Radical hysterectomy versus radiation therapy for stage IB squamous cell cancer of the cervix. Cancer 1991;68:272–7.
5. Perez CA, Grigsby PW, Nene SM, Camel HM, Galakatos A, Kao MS, et al. Effect of tumor size on the prognosis of carcinoma of the uterine cervix treated with irradiation alone. Cancer 1992;69:2796–806.
6. Piver MS, Marchetti DL, Patton T, Halpern J, Blumenson L, Driscoll DL. Radical hysterectomy and pelvic lymphadenectomy versus radiation therapy for small (less than or equal to 3 cm) stage IB cervical carcinoma. Am J Clin Oncol 1988;11:21–4.
7. Frumovitz M, Sun CC, Schover LR, Munsell MF, Jhingran A, Wharton JT, et al. Quality of life and sexual functioning in cervical cancer survivors. J Clin Oncol 2005;23:7428–36.
8. Cohn DE, Swisher EM, Herzog TJ, Rader JS, Mutch DG. Radical hysterectomy for cervical cancer in obese women. Obstet Gynecol 2000;96:727–31.
9. Finan MA, Hoffman MS, Chambers R, Fiorica JV, DeCesare S, Kline RC, et al. Body mass predicts the survival of patients with new International Federation of Gynecology and Obstetrics Stage IB1 and IB2 cervical carcinoma treated with radical hysterectomy. Cancer 1998;83:98–102.
10. Levrant SG, Fruchter RG, Maiman M. Radical hysterectomy for cervical cancer: morbidity and survival in relation to weight and age. Gynecol Oncol 1992;45:317–22.
11. Soisson AP, Soper JT, Berchuck A, Dodge R, Clarke-Pearson D. Radical hysterectomy in obese women. Obstetrics and gynecology 1992;80:940–3.
12. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chron Dis 1987;40:373–83.
13. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 2003;348:1625–38.
14. Wang Y, Beydoun MA. The obesity epidemic in the United States–gender, age, socioeconomic, racial/ethnic, and geographic characteristics: a systematic review and meta-regression analysis. Epidemiol Rev 2007;29:6–28.
15. Wee CC, Phillips RS, McCarthy EP. BMI and cervical cancer screening among white, African-American, and Hispanic women in the United States. Obes res 2005;13:1275–80.
16. Eisenkop SM, Spirtos NM, Montag TW, Moossazadeh J, Warren P, Hendrickson M. The clinical significance of blood transfusion at the time of radical hysterectomy. Obstet Gynecol 1990;76:110–3.
17. Morris PC, Haugen J, Tomjack J, Anderson B, Buller RE. Blood transfusion and the risk of recurrence in stage IB cervical cancer. Gynecol Oncol 1995;57:401–6.
18. Monk BJ, Tewari K, Gamboa-Vujicic G, Burger RA, Manetta A, Berman ML. Does perioperative blood transfusion affect survival in patients with cervical cancer treated with radical hysterectomy? Obstet Gynecol 1995;85:343–8.
19. Azuma C, Koyama M, Inagaki M, Ito S, Sawada M, Saji F, et al. The influence of peri-operative blood transfusion during radical hysterectomy on the prognosis of uterine cervical cancer. Transfus Sci 1997;18:55–62.
20. Lentz SS, Shelton BJ, Toy NJ. Effects of perioperative blood transfusion on prognosis in early-stage cervical cancer. Ann Surg Oncol 1998;5:216–9.
21. Spirtos NM, Westby CM, Averette HE, Soper JT. Blood transfusion and the risk of recurrence in squamous cell carcinoma of the cervix: a gynecologic oncology group study. Am J Clin Oncol 2002;25:398–403.
22. Frumovitz M, dos Reis R, Sun CC, Milam MR, Bevers MW, Brown J, et al. Comparison of total laparoscopic and abdominal radical hysterectomy for patients with early-stage cervical cancer. Obstet gynecol 2007;110:96–102.
23. Slomovitz BM, Ramirez PT, Frumovitz M, Soliman PT, Bevers M, Coleman RL, et al. Electrothermal bipolar coagulation for pelvic exenterations. Gynecol Oncol 2006;102:534–6.
24. Jensen PT, Groenvold M, Klee MC, Thranov I, Petersen MA, Machin D. Longitudinal study of sexual function and vaginal changes after radiotherapy for cervical cancer. Int J Radiat Oncol Biol Phys 2003;56:937–49.
© 2008 The American College of Obstetricians and Gynecologists
25. Schover LR, Fife M, Gershenson DM. Sexual dysfunction and treatment for early stage cervical cancer. Cancer 1989;63:204–12.