Fertility-sparing Options for Ovarian Cancer Patients
Fertility-sparing Options for Ovarian Cancer Patients
Abstract & Commentary
By Robert L. Coleman, MD, Professor, University of Texas; M.D. Anderson Cancer Center, Houston, is Associate Editor for OB/GYN Clinical Alert.
Dr. Coleman is a consultant to GlaxoSmithKline, Eli Lilly Co., Abbott Laboratories, Sanofi-Aventis, and Pfizer; and serves on the speakers bureaus for GlaxoSmithKline, Eli Lilly Co., and OrthoBiotech.
Synopsis: While ovarian cancer is predominately characterized by advanced stage presentation in women of menopausal age, a fraction is diagnosed in those with otherwise intact reproductive potential. The safety of organ preservation was addressed in this SEER-based registry study. Using survival as a metric, conservation of at least 1 ovary and the uterus appeared to be safe in women with stage IA or IC disease. As life-long complications of ovarian castration are becoming more evident, the implications of this study would appear to extend beyond fertility preservation.
Source: Wright JD, et al. Fertility preservation in young women with epithelial ovarian cancer. Cancer 2009 Aug 10; Epub ahead of print; doi: 10.1002/cncr.24461.
The standard surgical approach to ovarian cancer in medically fit patients is extirpation of the uterus, tubes, and ovaries, along with systematic staging or debulking of metastatic disease. The result should be removal of all potentially relevant cancer-bearing tissues and tumor residuum as this endpoint has been associated with superior survival. While not the norm, a fraction of patients presents with limited-stage disease in ages where fertility preservation is a potential consideration.
To evaluate the outcome of subtotal resection/organ-sparing surgery in women of fertility consideration, the authors examined data from the SEER (Surveillance, Epidemiology and End Results) database from 1988 to 2004. They examined the outcomes of women undergoing removal of a single or part of an ovary, with or without malignant ascites or capsular extension (ovarian conservation stage IA and IC) compared to those women of similar stages in whom both ovaries were removed (oophorectomy stage IA and IC). They also examined a cohort of women with stage IA or IC disease in whom the uterus was also left behind at surgery and compared their survival to those undergoing hysterectomy. All patients in both demographics had epithelial ovarian carcinomas. In the ovarian cohort, 1186 women were identified, of whom 432 (36%) underwent ovarian conservation surgery. In the uterine preservation cohort, 2911 women were identified, 679 (23%) of whom had conservative surgery.
Compared to their total resection counterparts, no difference in survival was observed for either preservation cohort; parity was maintained even when controlling for stage. Younger age, later year of diagnosis, and residence in the eastern or western United States were associated with greater likelihood of ovarian preservation. Women with endometrioid and clear cell histology and stage IC disease were less likely to have ovarian conservation. Uterine preservation was more likely in women with similar characteristics, but also included single marital status, mucinous tumors, and stage IA disease. Uterine conservation was similarly unassociated with survivorship. The authors concluded that ovarian and uterine-sparing surgery is safe in women of childbearing age with stage IA and IC disease.
Commentary
There is no doubt that the results of this trial will be welcomed news to the minority of women diagnosed with epithelial ovarian cancer in their reproductive years. While not the first to suggest subtotal resection of the reproductive tract is associated with good outcomes, the current report lends some confidence that large differences in survivorship between those undergoing organ-sparing surgery and those undergoing complete extirpation is not a high probability. And since the question of fertility-sparing surgery cannot realistically be answered in a prospective, randomized trial, these data likely represent our best hypothesis generating material to date.
However, the data should be viewed cautiously. While there appears to be no immediate impact on survivorship in either of the cohorts, the question underlying the analysis, namely fertility preservation, was untested in the analysis. It is likely that many of these patients, particularly those with incomplete staging and those with stage IC disease received adjuvant chemotherapy or radiation therapy. It is unknown and not reported whether fecundity was preserved in those wishing to preserve it. In addition, patterns of recurrence are not available in the database and it is unknown what the impact of these occurrences could have had on fertility. Further confounding the analysis, classification bias could not be controlled for as patients could have previously undergone unilateral oophorectomy for benign indication and show up in the SEER database as a unilateral or subtotal resection but without viable ovarian tissue. Finally, there was no central pathology review, limiting the impact of the histology to a myriad of interpretations from the reporting sites; indeed those with clear cell and endometrioid histology were less likely to have organ preservation than those with other histologies. Nevertheless, the study provides useful information to aid the informed consent process with prospective patients contemplating their surgical options.
Suggested Readings
- Trimbos JB, et al. Two parallel randomized phase III trials of adjuvant chemotherapy in patients with early-stage ovarian carcinoma. J Natl Cancer Inst 2003;95:105-112.
- Schilder JM, et al. Outcome of reproductive age women with stage IA or IC invasive epithelial ovarian cancer treated with fertility-sparing therapy. Gynecol Oncol 2002;87:1-7.
- Raspagliesi F, et al. Conservative surgery in high-risk epithelial ovarian carcinoma. J Am Coll Surg 1997;185:457-460.
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