Relative influences of tumor volume before surgery and the cytoreductive outcome on survival for patients with advanced ovarian cancer: a prospective study

Abstract

Objective

The purpose of this study was to determine the relative influences of the extent of disease present before surgery and completeness of cytoreduction on survival for patients with advanced ovarian cancer.

Methods

Patients (408) with stage IIIC epithelial ovarian cancer had cytoreductive surgery before systemic platinum-based combination chemotherapy. A ranking system (0–3) was devised to prospectively quantify the extent of disease involving: (1) right upper quadrant (diaphragm/hepatic, and adjacent peritoneal surfaces), (2) left upper quadrant (omentum/gastro-colic ligament, spleen, stomach, transverse colon, splenic flexure of colon), (3) pelvis (reproductive organs, recto-sigmoid, pelvic peritoneum), (4) retroperitoneum (pelvic/aortic nodes), and (5) central abdomen (small bowel, ascending/descending colon, mesentery, anterior abdominal wall, pericolic gutters). Survival was analyzed (log rank and Cox regression) on the basis of the rankings at these anatomic regions, the sum of intraabdominal rankings, and the cytoreductive outcome.

Results

Overall median and estimated 5-year survivals were 58.2 months and 49%. On univariate analysis, the central abdominal (P = 0.008) and left upper quadrant (P = 0.03) rankings, the sum of rankings (P = 0.01), and the cytoreductive outcome (P ≤ 0.0001) influenced survival (log rank). Survival was independently (stepwise Cox model) influenced by the sum of rankings (0–5, RR 1.00; 6–10, RR 1.24; 11–15, RR 1.44; P = 0.05), and completeness of cytoreduction (visibly disease-free, RR 1.00; ≤1 cm residual, RR 2.32; >1 cm residual, RR 2.98; P = 0.001).

Conclusions

Cytoreduction to a visibly disease-free outcome has a more significant influence on survival than the extent of metastatic disease present before surgery. Operative efforts should not be abbreviated on the hypothesis that extensive disease at specific anatomic regions precludes long-term survival.

Introduction

Multiple series report the completeness of primary cytoreductive operations to independently influence survival for patients with advanced epithelial ovarian cancer [1], [2], [3], [4], [5], [6], [7], [8]. Median and 5-year survivals after removal of all visible disease before treatment with chemotherapy are reported to exceed survival resulting from “optimal” procedures with unresected small volume (≤1 cm) residual disease [1], [2], [3], [4], [6], [7]. However, both “optimal” and complete cytoreduction are more easily achieved for small intraabdominal tumor burdens than large ones [4], [7], [9]. In addition to being a greater surgical challenge, ovarian cancers diagnosed with massive, widespread intraabdominal disease are suggested to have natural histories that may be unalterable due to innate tumor biology, even if “optimal” or complete cytoreduction is achieved [10], [11], [12], [13]. Hence, it has been proposed that tumor biology may play a more significant role in determining survival than the operative outcome for patients with extensive intraabdominal disease [10], [11], [12], [13]. In this study a numerical ranking system quantifies the extent of disease at five intraabdominal anatomic regions before cytoreduction. It is applied to investigate relative influences of the extent of disease present before surgery and completeness of primary cytoreduction on survival for patients with advanced ovarian cancer.