Milam, Michael R. MD; Sood, Anil K. MD; King, Sara MSPH; Bassett, Roland L. Jr MS; Lu, Karen H. MD; Slomovitz, Brian M. MD; Coleman, Robert L. MD; Ramirez, Pedro T. MD
Ovarian cancer is the second most common gynecologic malignancy in the United States but is associated with the highest mortality rate among gynecologic cancers.1 Unfortunately, nearly 75% of patients with ovarian cancer are diagnosed with advanced-stage disease. The typical recommendation for these patients is to undergo tumor-reductive surgery. This procedure usually entails total abdominal hysterectomy (TAH; removal of the cervix and uterus through an incision in the abdominal wall) and removal of the ovaries, omentum, and all additional sites of visible disease.2 Recently, however, it has been proposed that supracervical hysterectomy (SCH), in which the uterus is removed but the cervix is left in place, may be an appropriate alternative to TAH in patients with ovarian cancer.
Supracervical hysterectomy is a generally accepted option in gynecologic surgery for benign indications.3 A recent survey of 369 gynecologic surgeons found that 88% of gynecologic oncologists in the United Kingdom and 50% of gynecologic oncologists in the United States would perform a SCH for benign indications.3 One proposed benefit of SCH is avoidance of adverse effects on bladder, bowel, and sexual function as a result of removal of the cervix; however, clear benefits of SCH over TAH have not been demonstrated in randomized trials.4 Additional potential benefits that have been suggested for SCH include reduced operating time, reduction in blood loss and transfusion rate, and a shorter recovery period.5
Although the traditional recommendations for patients with ovarian cancer have included TAH, some oncologists have recently recommended SCH rather than TAH in patients with ovarian cancer who will receive intraperitoneal chemotherapy because SCH may limit vaginal leakage of the chemotherapy agents.6,7 In addition, a report of a vaginal recurrence of ovarian cancer after TAH in a patient with widespread peritoneal disease8 raised the possibility that SCH rather than TAH in such patients may decrease the risk of tumor erosion by limiting peritoneal contact with the vaginal mucosa.
If SCH is not associated with increased perioperative complication rates, increased local recurrence rates, or decreased overall survival compared with TAH, it may be a reasonable option in patients with ovarian cancer. However, to the best of our knowledge and according to a MEDLINE search (limited to the English language from January 1, 1950, to October 1, 2006, using the keywords “supracervical,” “hysterectomy,” and “ovarian cancer”), there are no published data that address the implications of SCH compared with TAH in the setting of advanced ovarian carcinoma. We hypothesized that performing SCH rather than TAH does not adversely affect the clinical outcomes of ovarian cancer patients. To test this hypothesis, we compared clinical outcomes in patients with advanced ovarian cancer who underwent SCH or TAH.
MATERIALS AND METHODS
After obtaining institutional review board approval from the M. D. Anderson Cancer Center Office of Protocol Research and a waiver of the need for informed consent, we used the gynecologic oncology tumor database at The University of Texas M. D. Anderson Cancer Center to identify patients with advanced (stage III or IV) ovarian cancer who underwent SCH or TAH at M. D. Anderson Cancer Center between 1993 and 2004. Patients were selected on the basis of age, year of surgery, histologic subtype, and stage. Patients with any of the following characteristics were excluded: benign disease, synchronous primary tumors, tumors of low malignant potential, incomplete clinicopathologic data, nonepithelial ovarian cancer, history of an additional primary tumor within the 5 years before or during the period after ovarian cancer diagnosis, BRCA gene mutations or hereditary nonpolyposis colorectal cancer, and non–advanced-stage disease.
Patient records were reviewed for clinical information regarding preoperative characteristics including age and preoperative CA 125 levels. The perioperative clinical factors of the study group were also reviewed along with complications that were reported within 30 days of initial surgery. The postoperative follow-up of our study population was focused on adjunctive therapy, tumor recurrence sites, and progression-free and overall survival. Epithelial ovarian cancer was defined as serous, mixed, endometrioid, or clear cell on the basis of the pathology reports. Ovarian cancer was staged according to International Federation of Gynecology and Obstetrics classification on the basis of the pathology reports and documented clinic notes.
The technique of SCH used most often in the patients in our series involved skeletonization of the uterine arteries bilaterally along with dissection of the vesicouterine fold to leave an area of approximately 1 cm below the internal cervical os. At the level of the internal cervical os, the uterine vessels were ligated and divided. At this point, the uterus was transected from the cervix was then closed with absorbable suture.
The extent of tumor cytoreduction was determined on the basis of the operative notes. Optimal cytoreduction was defined as residual tumor implants not larger than 1 cm in the pelvis or abdomen. Intraoperative complications were recorded from time of incision to end of procedure.
Typical patient follow-up included a postoperative visit with review of the pathology report at 1–2 weeks and subsequent visits every 3–4 weeks for chemotherapy. Chemotherapy generally consisted of an intravenous platinum-based agent (carboplatin or cisplatin), with the majority of patients also receiving paclitaxel. After completion of all therapy, patients were seen at 3-month intervals during the first year and at 6-month intervals during years 2–5. Serial serum CA 125 measurements and pelvic examinations were done at each follow-up visit unless reinitiation of chemotherapy was indicated. During our review of the records from the postoperative visits, we paid special attention to documentation of findings on pelvic examination indicating local recurrence. Recurrence rates and follow-up examinations were documented only if recorded in our clinical charts.
For statistical analysis, independent-sample t tests and log rank tests were used to compare groups for continuous variables. For categorical variables, Fisher exact test was used to compare the proportions between groups. The Kaplan-Meier method was used to estimate the distribution of the time to end point. A P<.05 was considered statistically significant.
We identified 47 patients who underwent SCH (mean age, 59.6 years) and met our inclusion criteria, and these patients were compared with a 190-patient TAH cohort. There were no significant differences between the two groups with respect to age, race, preoperative serum CA 125 level, or receipt of taxane- and platinum-based chemotherapy (Tables 1 and 2). Although both groups of patients were eligible for numerous study protocols there were no significant differences between the SCH and TAH groups in regard to study protocols (1 of 47 or 2.1% compared with 16 of 190 or 8.4%; P=.21). Indications for SCH included concerns about patient blood loss (4 of 47 patients, or 8.5%); tumor involvement (16 of 47, or 34%); and surgeon preference (27 of 47, or 57.4%). Tumor involvement was defined as tumor involvement of the cul-de-sac, tumor involvement of the posterior wall of the bladder, or other anatomic distortions of the pelvic organs by tumor. When the operative report did not list concerns about blood loss or tumor involvement as indications for SCH, the indication was assumed to be surgeon preference.
There was no significant difference between the SCH and TAH groups in the rate of intraoperative complications (P=.24). Intraoperative complications were defined as damage to bowel or bladder or vascular injury. The TAH group had a greater proportion of patients with optimal tumor cytoreduction (123 of 190, or 64.7%, compared with 14 of 47, or 30%; P<.001). Rates of patients with postoperative issues requiring readmission were also similar in the SCH and TAH groups (P=.75).
One hundred seventy-three (87.4%) of 198 patients had progression or recurrence after initial surgery and chemotherapy. There were no significant differences between the SCH and TAH groups in progression or recurrence rates (66% and 75%; P=.48).
There were no significant differences in taxane- and platinum-based chemotherapy regimens (P=.84) between the two groups. Rates of follow-up gynecologic complaints (vaginal bleeding, vaginal discharge, or dysuria) were similar in the two groups: 5.7% (2 of 35) in the SCH group and 5.6% (8 of 142) in the TAH group. There were no significant differences between the SCH and TAH groups in vaginal or cervical recurrence rates (10.6% and 11.6%; P=1.00) (Table 2), or in progression-free survival (SCH of 1.01 years compared with TAH of 1.19 years; P=.64) or overall survival (SCH of 3.28 years compared with TAH of 3.36 years; P=.12) (Figs. 1 and 2). There were no reported difficulties in physical examinations in the SCH group due to the presence of the cervical stump. Overall survival remained similar between the two groups (P=.36) after adjustment for degree of cytoreduction (TAH/optimal of 3.72 years compared with TAH/suboptimal surgery of 3.02 years and SCH/optimal of 3.62 years compared with SCH/suboptimal surgery of 3.11 years; P=.37; Fig. 4). In both the SCH group and the TAH group, optimal cytoreduction was associated with significantly better progression-free survival (P<.001) and overall survival (P<.02) than suboptimal cytoreduction (Fig. 3). There were 7 reported cases of tumor erosion into the vagina in the TAH group (7 of 190, 3.7%, 95% confidence interval 1.5–7.4%; P=.35) compared with none in the SCH group. Local radiotherapy was used to treat three of the seven cases (43%) of tumor erosion into the vagina.
In our study, there is no evidence that patients treated with SCH rather than TAH during initial tumor-reductive surgery for advanced epithelial ovarian cancer have different local recurrence rates, complication rates, or survival. We also found a lower rate of vaginal tumor erosion in the SCH group than in the TAH group, although this difference did not reach statistical significance.
Optimal tumor cytoreduction has been associated with improved overall survival in several retrospective studies and has been incorporated into the standard of care.9 The benefits of optimal cytoreduction have even been reported in patients with stage IV disease.10 In our current series of patients with advanced epithelial ovarian cancer, optimal tumor cytoreduction was associated with a significantly improved overall survival compared with patients with suboptimal cytoreduction.
At present, SCH is not routinely performed or recommended at M. D. Anderson. However, SCH may merit further consideration given the findings of our present study and the recent findings of improved survival in patients treated with intraperitoneal chemotherapy for ovarian cancer.11 A reported barrier to the completion of all cycles of intraperitoneal chemotherapy was leakage of chemotherapeutic agent through the vaginal cuff.6,7 If SCH is confirmed to result in clinical outcomes similar to those after TAH, as suggested by our current study, then SCH may be the surgery of choice for patients scheduled to undergo intraperitoneal chemotherapy because of the benefit of prevention of vaginal leakage of the chemotherapy agent.
One could argue that SCH is not advisable for surgical cytoreduction in patients with advanced ovarian cancer because of the potential for disease progression in the residual cervical stump and subsequent bleeding. However, we found similar local recurrence rates in the TAH and SCH groups (16.3% and 16.7%; P=1.00). Another argument against SCH is that the remaining cervical stump could complicate subsequent physical examinations performed for surveillance of disease. We did not observe any reported difficulties in physical examinations in the SCH group due to the presence of the cervical stump.
An argument in favor of SCH is that SCH may be associated with a decreased length of surgery and diminished overall blood loss. However, this has not been proven in prospective series.12 In our study, operative time, blood loss, and transfusion rates in the SCH group were similar to those in the TAH group.
There are several inherent limitations of a retrospective study design. Confounding variables, along with selection and information biases, are always possible. However, in this study we attempted to limit their effects. We selected all cases from a single institution on the basis of age, stage, histologic subtype, and date of surgery. The fact that the TAH group had a greater percentage of patients with optimal tumor cytoreduction potentially complicates interpretation of our results. However, the more complete tumor cytoreduction in the TAH group makes the findings of similar survival and recurrence rates in the two groups even more compelling in favor of SCH. However, it may be that we did not have a large enough sample size to demonstrate a significant difference between the SCH and TAH groups with respect to survival. Unfortunately, demonstrating statistical equivalence or noninferiority requires a large sample size, much larger than the number of patients that were available for this study. Thus, we are not able to conclude that the groups are equivalent. However, we can address the power of our study to detect certain differences. For example, given the sample sizes of 47 in the SCH group and 190 in the TAH group, if the proportion of intraoperative complications was 3.7% in the TAH group, we would have had 80% power to detect an increase in this rate to 16% in the SCH group, assuming a two-tailed alpha=0.05 level test. In addition, we wish to make it clear in our conclusions that there is no evidence of a difference between TAH and SCH, not that there is no difference.
We conclude that SCH in patients diagnosed with advanced epithelial ovarian cancer may be a reasonable alternative to TAH if clinically indicated. Clinical indications reported by the gynecologic oncologists at this institution included large tumor plaques in the cul-de-sac, tumor involving the posterior cervix and extending into the rectovaginal space, desire for minimization of blood loss, and surgeon preference. Reasonable indications for SCH may also include, in the setting of optimal cytoreduction, patients who may receive intraperitoneal chemotherapy. The option of SCH should be reviewed with patients preoperatively during a discussion of potential indications for and benefits of different surgical techniques.
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© 2007 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.