Factors that influence survival in high-grade serous ovarian cancer: A complex relationship between molecular subtype, disease dissemination, and operability

Objective: To investigate the relationship between molecular subtype, intraperitoneal (IP) disease dissemination patterns, resectability, and overall survival (OS) in advanced high-grade serous ovarian cancer (HGSOC).

Methods: Patients undergoing primary surgery for stage III-IV HGSOC at Mayo Clinic from 1994 to 2011 were categorized into three IP disease dissemination patterns: upper abdominal or miliary; lower abdominal; and pelvic. Residual disease was defined as 0 (RD0), 0.1-0.5, 0.6-1.0, or >1 cm. Molecular subtypes were derived from Agilent 4x44k tumor mRNA expression profiles and categorized as mesenchymal (MES) or non-mesenchymal (non-MES).

Results: Operative and molecular data was available for 334 patients. Median OS was shorter in patients with MES compared to non-MES subtypes (34.2 vs 44.6 months; P = 0.009). Patients with MES subtype were more likely to have upper abdominal/miliary disease compared to non-MES subtype (90% vs. 72%, P < 0.001). For patients with upper abdominal/miliary disease, complete resection (RD0) was less common in MES compared to non-MES subtypes (11% vs. 27%, P = 0.004). On multivariable analysis, RD was the only factor associated with OS (P < 0.001). In patients with upper abdominal/miliary disease, though less commonly achieved, RD0 improved survival irrespective of molecular subtype (median OS of 69.2 and 57.9 months for MES and non-MES subtype).

Conclusions: Our results support a paradigm in which molecular subtype is an important driver of dissemination pattern; this in turn impacts resectability and ultimately survival. Consequently mesenchymal subtype is associated with much lower rates of complete resection, though RD0 remains the most important independent predictor of survival.