Intraoperative Capsule Rupture in Stage 1 Epithelial Ovarian Cancer

Ovarian cancer is the most common cause of gynecological cancer-related deaths in developed countries. Generally, suspected tumors that appear to be confined to the ovary are targeted via adnexectomy, and this procedure can result in surgical spill in up to 48% of cases.¹ In 2014, the International Federation of Gynecology and Obstetrics (FIGO) established intraoperative capsule rupture as its own category of ovarian cancer staging, known as IC1. Although various guidelines advise postoperative chemotherapy for high-risk ovarian cancer with stage IC disease, to date no recommendations have been published specifically for cases of IC1.¹

Additionally, although previous studies have linked capsule rupture to decreased survival, disagreement persists over its true impact on prognosis. A benchmark nationwide study in Obstetrics and Gynecology examined the incidence and prognostic significance of capsule rupture on the 4 major histology types of IA-IC1 epithelial ovarian cancer (serous, mucinous, endometrioid, and clear cell), its impact on oncologic outcome, and the efficacy of postoperative chemotherapy.¹

Clear cell histology shows disproportionate rupture risk

Drawing from the Gynecologic Tumor Registry database of the Japan Society of Obstetrics and Gynecology, this retrospective study captured over 15,000 cases of stage IA-IC1 ovarian cancer, particularly T1a-1c1, N0-x, M0-x, between 2002 and 2015. A total of 7227 (47.7%, 95% confidence interval [CI] 46.9–48.5) incidences of intraoperative capsule rupture were examined.¹

Investigators observed that independent predictors for intraoperative capsule rupture included age at diagnosis, lymphadenectomy performance, and histology type. The histology most likely to rupture was clear cell (57.3%), followed by endometrioid (48.8%), serous (41.8%), and mucinous (32.0%) (absolute difference, 25.3% P<.001). The risk of rupture in clear cell tumors was disproportionately high, occurring at a rate nearly 3 times greater than that of mucinous (P<.001) and approximately 40% greater than that of endometrioid (P<.001).¹

Critically, young women—57 and younger—with clear cell tumors showed the highest risk of capsule disruption (60.9%). The authors noted that this observed increased risk may be related to endometriosis, as clear cell tumors are associated with the disease both epidemiologically and biologically, and surgical removal of endometriomas carries a high risk of rupture.¹

Prognostic significance of rupture varies among subtypes

Survival analyses of 7484 women with a median follow-up time of 5.1 years revealed 403 ovarian cancer-related deaths. However, the prognostic significance of rupture varied across histology types. Clear cell showed the strongest association with decreased survival (hazard ratio [HR] 1.99, 95% CI 1.45–2.75), followed by serous (HR, 1.61, 95% CI 0.84–3.11), mucinous (HR 1.28, 95% CI 0.79–2.09), and endometrioid (HR, 1.14, 95% CI 0.64–2.01) after adjustment.¹

Postoperative chemo not associated with change in survival

Among patients who experienced intraoperative capsule rupture (n=7227), 5646 (78.1%, 95% CI 77.2–79.1) subsequently underwent chemotherapy. However, postoperative chemotherapy did not increase cause-specific survival for patients with any subtype (all, P>.05). In fact, those who received chemotherapy showed similar survival to patients who did not receive this therapy, including those with clear cell (adjusted HR 0.86, 95% CI 0.56–1.31), serous (adjusted HR 1.08, 95% CI 0.42–2.74), mucinous (adjusted HR 1.11, 95% CI 0.55–2.27), and endometrioid (adjusted HR 2.81, 95% CI 0.85–9.30) tumors.¹

Interestingly, between 2002 and 2015, far fewer ovarian cancer patients received postoperative chemotherapy, particularly those with mucinous (16.3% relative decrease), endometrioid (13.1% relative decrease), and clear cell (9.3% relative decrease) types. However, despite this trend, the 5-year cause-specific survival rates did not change. The study’s authors attribute the significant decrease in postoperative chemotherapy to a growing awareness of its potentially negligible impact, though future prospective studies are warranted to further assess its necessity.¹

Impact on clinical decision-making

Because capsule rupture and its associated upstaging decrease survival, the findings of this study have important implications in surgical decision-making. Peritoneal washings should be used in staging of suspicious ovarian masses. Furthermore, if surgeons face challenges during the laparoscopic approach, and the tumor is confined to the ovary, early conversion to a laparotomy may be appropriate.¹

Future directions for research

As the data from the present study were drawn from a Japanese database, the generalizability of these results in other populations remains to be proven in future research. Additionally, these data show an association between capsule rupture and registry location, a relationship that suggests a connection between disease etiology and geographic disparity, and calls for further exploration.¹

MedPage Today spoke with the study’s principal investigator, Koji Matsuo, MD, PhD, Department of Obstetrics and Gynecology, University of Southern California, who offered another direction for future research. “There is an increasing trend of minimally invasive surgery in gynecological disease in recent years,” he said. “It will be paramount to examine if minimally invasive surgery for ovarian cancer, apparently confined to the ovary, is associated with increased risk of intraoperative capsule rupture.”

Published: July 17, 2020