Intraperitoneal disease dissemination patterns are associated with residual disease, extent of surgery, and molecular subtypes in advanced ovarian cancer

Abstract

Objective To investigate the association between intraperitoneal (IP) disease dissemination patterns, residual disease (RD), surgical complexity, and molecular subtypes in advanced high-grade serous ovarian cancer (HGSOC). Methods 741 patients with operable stage III–IV HGSOC undergoing primary debulking surgery at Mayo Clinic from 1994–2011 were categorized into four mutually exclusive IP disease dissemination patterns: upper abdominal (60%), miliary (16%), lower abdominal (15%), and pelvic (9%). Surgical complexity was classified as high, intermediate, or low; RD status was defined as 0, 0.1–0.5, 0.6–1.0, or >1 cm; molecular subtype assignments were derived from expression profiling of tumors from 334 patients. Results Patients with either miliary or upper abdominal dissemination patterns were less likely to achieve RD0 compared to patients with pelvic and lower abdominal dissemination patterns (25% vs. 9% and 62%, each P<0.001) despite higher surgical complexity (39% vs. 6% and 20%, each P<0.001). Among the subset with molecular subtype data, patients with mesenchymal subtype of tumors were more likely to have upper abdominal or miliary dissemination patterns compared to patients with differentiated, proliferative, or immunoreactive subtypes (90% vs. 77%, 70%, 69%, respectively, P<0.05). Conclusions IP disease dissemination patterns are associated with RD, surgical complexity, and tumor molecular subtypes. Patients with upper abdominal or miliary dissemination patterns are more likely to have mesenchymal HGSOC and in turn achieve lower rates of complete resection. This provides a plausible model for how the biologic behavior of molecular subtypes is manifest in disease and oncologic outcomes.

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

“…Molecular classification of high-grade serous ovarian cancer (HGSOC) using tumor mRNA profiling was first described by Tothill et al [1] and has been independently confirmed by multiple studies, including our own [2,3]. We subsequently demonstrated that molecular subtypes are associated with intraperitoneal (IP) disease dissemination patterns and surgical outcomes in advanced HGSOC [2][3][4]. The relationship between molecular subtype, dissemination patterns, and residual disease (RD) is complex.…”

“…Patients with borderline tumors, those who were treated with neoadjuvant chemotherapy, and those without research consent or molecular profiling were excluded. IP disease dissemination patterns among eligible patients with stage III and stage IV HGSOC were defined into four categories using our previously published criteria [4]: pelvic disease, lower abdominal disease, upper abdominal disease, and miliary disease (Supplementary Table S1). Four RD groups were defined, RD0, RD 0.1-0.5 cm, RD 0.6-1.0 cm, RD N1 cm, based on the largest residual tumor diameter.…”

“…Surgical complexity was assigned using previously published methods and classified as low, intermediate, or high complexity surgery [10]. Since patients with upper abdominal or miliary disease have similar surgical outcomes [4], we combined the two into one IP disease dissemination pattern for all statistical comparisons.…”

“…1). Even among patients with upper abdominal/miliary disease, the rate of complete resection (RD0) is lower in patients with MES compared to non-MES tumors [4]. This appears to reflect, in part, both the driving effect of molecular characteristics on disease spread, and the complex interaction between tumor biology and resectability of disease in advanced HGSOC.…”

“…The relationship between molecular subtype, dissemination patterns, and residual disease (RD) is complex. Patients with mesenchymal (MES) subtype are more likely to present with disease in the upper abdomen [4] and, in turn, disease in the upper abdomen is more difficult to resect [4][5][6][7]. Irrespective of dissemination pattern, MES tumors are more difficult to completely resect (RD0) than non-MES tumors (Fig.…”