Primary cytoreductive surgery and adjuvant hormone therapy in women with advanced low-grade serous carcinoma: Reducing overtreatment without compromising survival?

Abstract

Objectives: Women with low-grade serous carcinoma (LGSC) of the ovary or peritoneum have low chemotherapy response rates and poor overall survival (OS) with advanced-stage disease. Most LGSC tumors overexpress hormone receptors, which represent a potential treatment target. Our study objective was to determine the safety and survival outcomes of patients with advanced-stage LGSC treated with cytoreductive surgery (CRS) and hormone therapy (HT) in the primary setting. Methods: A retrospective study at two academic cancer centers was performed. Patients with stage II–IV LGSC underwent either primary or interval CRS, followed by adjuvant HT, between 2004 and 2014. Expert gynecologic pathologists reviewed all cases. Data on patient, surgical, and treatment variables were collected. Median progression-free survival (PFS) and OS were calculated. Outcomes were compared with those of an age- and stage-matched LGSC control group treated with CRS and chemotherapy. Results: Twenty-six patients with LGSC were treated with CRS + HT. Primary CRS + HT was administered in 25 patients, and neoadjuvant chemotherapy followed by CRS + HT was administered in 1 patient. The median patient age was 46.5 years, and patients had stage II (n = 4), stage IIIA (n = 6), stage IIIC (n = 15), and stage IV (n = 1) disease. Optimal CRS to no apparent gross residual disease was achieved in 81.5%, optimal CRS less than 1 cm in 14.8%, and suboptimal CRS in 3.7%. The patient treated with neoadjuvant chemotherapy had extensive carcinomatosis and liver metastases (stage IV) that progressed with chemotherapy; after CRS, she has been progression-free for 15 months with shrinking liver implants on HT. Anastrozole was administered postoperatively in 55.6%, letrozole in 37.0%, and tamoxifen in 7.4%. The median time for HT was 18 months. After a median follow-up of 28 months (range, 10–126 months), 4 patients (14.8%) developed a recurrence. All initial abdominopelvic recurrences were salvaged with CRS with or without chemotherapy or HT. Three patients (11.5%) are alive with disease, and 23 (88.5%) have no evidence of disease. The median PFS was 22 months and median OS was not yet reached. Compared with a control group of 44 patients with LGSC treated with CRS + chemotherapy (median PFS: 21 months, median OS: 70 months), the survival of the HT-treated cohort was not significantly different. Conclusions: Our series describes the initial experience with CRS and HT for primary advanced-stage LGSC. Although surgery remains the mainstay of therapy, cytotoxic chemotherapy may not be necessary in the primary setting. These results merit further investigation in a prospective trial.