Fertility-sparing Surgery in Ovarian Cancer: Is It Safe?
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 bureau for GlaxoSmithKline, Eli Lilly Co., and OrthoBiotech.
Synopsis: Patients with early-stage ovarian cancer can in many circumstances be treated with conservative surgery enabling subsequent fertility options. However, options are more limited for those with grade 3 tumors and prudence should be exercised when adjuvant chemotherapy is indicated.
Source: Satoh T, et al. Outcomes of fertility-sparing surgery for stage I epithelial ovarian cancer: A proposal for patient selection. J Clin Oncol 2010;28:1727-1732.
Early-stage ovarian cancer is frequently associated with younger patients, some of whom may be interested in fertility preservation. The objective of this retrospective, multicenter survey was to assess the clinical outcomes and fertility in patients treated conservatively for unilateral stage I invasive epithelial ovarian cancer. In all, 211 patients underwent unilateral oophorectomy or cystectomy for apparent localized disease. Histology, grade, description of capsular rupture at exploration, adjuvant surgical procedures, such as omentectomy and lymph node evaluation, cytology, and use of adjuvant chemotherapy were recorded. The authors classified "favorable" histology as grade 1 or grade 2 adenocarcinoma, excluding clear cell histology. Stage IC was subclassified on the basis of capsular rupture vs tumor on the external surface vs positive cytology. Most of the patients had stage IA disease (60%); the remainder was stage IC. Staging operations were not performed in 52% of patients and when done, were complete in just 13%. Nevertheless, 5-year overall and recurrence-free survival were 100% and 98% for stage IA/favorable histology, 100% and 100% for Stage IA/clear cell histology, 100% and 33% for stage IA/grade 3, 97% and 92% for stage IC/favorable histology, 93% and 66% for Stage IC/clear cell histology, and 67% and 67% for stage IC/grade 3. Forty-five (53.6%) of 84 patients who attempted conception gave birth to 56 healthy children. The authors conclude that fertility-sparing surgery is a safe treatment for stage IA patients with favorable histology and suggest that stage IA patients with clear cell histology and stage IC patients with favorable histology can be candidates for fertility-sparing surgery followed by adjuvant chemotherapy.
Commentary
In light of its clinical reputation, ovarian cancer is seldom considered a disease where fertility-sparing options abound. In fact, we have made it a battle cry to formally stage patients with apparent limited invasive disease because metastatic disease is found in nearly a third and failure to recognize this can have lethal consequences. This being said, patients with limited disease are typically younger, have more favorable histology, and many will be cured with local extirpation alone. Fertility preservation may be an acceptable option for these women. Unfortunately, evidence to support this recommendation remains elusive, and what's available is contradictory at times, marred by retrospective interpretation, collected over prolonged enrollment periods, and limited by inconsistent surgical and adjuvant chemotherapy management patterns. Nevertheless, the current report has amassed enough data to raise the hypothesis that certain cohorts of these patients may be safely managed conservatively with favorable survival and normal fecundity. The data are summarized in the Table (below). However, it is important to recognize that even in this relatively large study, the number of patients in each category is unbalanced and may be too small to make an interpretation, and there are considerations that may confound their recommendations. For instance, 60% of the patients were of mucinous histology. Since most mucinous tumors present with limited stage disease, this histology over-represents the favorable category and limits interpretation of safety in the other histologies. Second, few patients underwent formal staging procedures. The authors' recommendations were influenced by what they termed "lethal recurrence," wherein subcategories of patients had unfavorable outcomes despite fertility-sparing procedures. An alternative conclusion may have been reached had staging pathology been available in these cases. It's of importance to note that while all patients with isolated recurrence in the residual ovary (n = 5) were salvaged with subsequent therapy, only 3 of 13 patients (23%) were salvaged when recurrence appeared outside of the residual ovary. Further, observed amenorrhea and secondary infertility accompanied the administration of chemotherapy, supporting their recommendation to exercise caution in patients with favorable histology and apparent stage IA disease; however, use of chemotherapy as adjuvant therapy is common in patients without proper staging information. This makes it more difficult in adjudicating the proper management strategy in a woman with apparent, but formally unstaged, limited disease who wishes to maximize survival and preserve fertility. Because it is essentially impossible to study fertility-sparing surgery by randomized trial, these data provide some confidence that this option is feasible for some patients.
| Table. Authors' recommendation regarding fertility-sparing surgery in appropriate patients with unilateral stage I ovarian cancer. | |||
Histology/Grade |
|||
Stage |
Favorable (mucinous, serous, endometrioid, grade 1 or 2) |
Clear cell |
Grade 3 |
IA |
Reasonable |
Optional but with chemotherapy |
Risky |
(n = 108; 100%/98%) |
(n = 15; 100%/100%) |
(n = 3; 100%/33%) |
|
IC |
Optional but with chemotherapy |
Risky |
Risky |
(n = 67; 97%/92%) |
(n = 15; 93%/66%) |
(n = 3; 67%/67%) |
|
Note: Summary of the number of patients and 5-year overall and relapse-free survival are in parentheses |
|||
Additional Reading
- Colombo N, et al. Controversial issues in the management of early epithelial ovarian cancer: Conservative surgery and role of adjuvant therapy. Gynecol Oncol 1994;55(3 Pt 2):S47-S51.
- Trimbos JB, et al. International Collaborative Ovarian Neoplasm trial 1 and Adjuvant ChemoTherapy In Ovarian Neoplasm trial: Two parallel randomized phase III trials of adjuvant chemotherapy in patients with early-stage ovarian carcinoma. J Natl Cancer Inst 2003;95:105-112.
- Vergote IB, et al. Analysis of prognostic factors in stage I epithelial ovarian carcinoma: Importance of degree of differentiation and deoxyribonucleic acid ploidy in predicting relapse. Am J Obstet Gynecol 1993;169:40-52.
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