A multicenter prospective trial evaluating the ability of preoperative computed tomography scan and serum CA-125 to predict suboptimal cytoreduction at primary debulking surgery for advanced ovarian, fallopian tube, and peritoneal cancer

Highlights

• Three clinical and six radiologic criteria associated with suboptimal cytoreduction were identified.

• A predictive model in which the suboptimal rate was directly proportional to a predictive value score was developed.

Abstract

Objective

To assess the ability of preoperative computed tomography (CT) scan of the abdomen/pelvis and serum CA-125 to predict suboptimal (> 1 cm residual disease) primary cytoreduction in advanced ovarian, fallopian tube, and peritoneal cancer.

Methods

This was a prospective, non-randomized, multicenter trial of patients who underwent primary cytoreduction for stage III–IV ovarian, fallopian tube, and peritoneal cancer. A CT scan of the abdomen/pelvis and serum CA-125 were obtained within 35 and 14 days before surgery, respectively. Four clinical and 20 radiologic criteria were assessed.

Results

From 7/2001 to 12/2012, 669 patients were enrolled; 350 met eligibility criteria. The optimal debulking rate was 75%. On multivariate analysis, three clinical and six radiologic criteria were significantly associated with suboptimal debulking: age ≥ 60 years (p = 0.01); CA-125 ≥ 500 U/mL (p < 0.001); ASA 3–4 (p < 0.001); suprarenal retroperitoneal lymph nodes > 1 cm (p < 0.001); diffuse small bowel adhesions/thickening (p < 0.001); and lesions > 1 cm in the small bowel mesentery (p = 0.03), root of the superior mesenteric artery (p = 0.003), perisplenic area (p < 0.001), and lesser sac (p < 0.001). A ‘predictive value score’ was assigned for each criterion, and the suboptimal debulking rates of patients who had a total score of 0, 1–2, 3–4, 5–6, 7–8, and ≥ 9 were 5%, 10%, 17%, 34%, 52%, and 74%, respectively. A prognostic model combining these nine factors had a predictive accuracy of 0.758.

Conclusions

We identified nine criteria associated with suboptimal cytoreduction, and developed a predictive model in which the suboptimal rate was directly proportional to a predictive value score. These results may be helpful in pretreatment patient assessment.

Introduction

Of the estimated 21,980 women diagnosed each year with primary ovarian, fallopian tube, or peritoneal carcinoma in the United States, the majority present with advanced-stage disease [1]. Standard initial therapy for these patients consists of primary cytoreductive surgery, or ‘debulking,’ followed by platinum and taxane-based chemotherapy [2].

Numerous studies have demonstrated a survival advantage for patients who undergo ‘optimal’ vs ‘suboptimal’ debulking [3], [4], [5], [6]. Although various cutoff points have been used to define optimal debulking (residual disease ranging from 0 to 3 cm), the Gynecologic Oncology Group (GOG) currently uses 1 cm as a cutoff [2]. While previously only of prognostic value, this stratification led to significant treatment implications with the publication of GOG–172, a randomized trial in women with optimally debulked (≤ 1 cm residual) ovarian cancer that showed a significant survival advantage for patients who received intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel compared to those who received intravenous paclitaxel and cisplatin chemotherapy [7]. Intraperitoneal chemotherapy is currently not a treatment option for suboptimally debulked women. It is also important to note that for patients who are suboptimally cytoreduced (> 1 cm residual), survival is equivalent regardless of residual tumor size [8], [9]. Reported rates of optimal cytoreduction vary widely in the literature, from 15% to 85% [10]. Therefore it appears that a significant proportion of women with advanced ovarian cancer will undergo a debulking procedure with associated morbidity but without a commensurate improvement in survival.

In order to determine which patients would be less likely to benefit from primary surgery, several attempts have been made to predict cytoreductive outcome, using imaging modalities, tumor markers, and laparoscopic scores [11]. Investigators have evaluated the utility of preoperative computed tomography (CT) scan in an effort to identify radiologic predictors, with inconsistent results [12], [13], [14], [15], [16]. The use of preoperative CA-125 has also been evaluated in this setting, with a cutoff value of 500 U/mL used by most researchers. Some studies have found CA-125 to be significantly associated with cytoreductive outcome, while others have not [17], [18], [19], [20], [21], [22], [23]. Studies attempting to identify preoperative predictors have been limited by their retrospective design, sample size, broad inclusion criteria, and heterogeneous rates of optimal cytoreduction. The objective of this trial was to prospectively assess the ability of preoperative CT scan of the abdomen/pelvis and serum CA-125 to predict suboptimal primary cytoreduction in patients with advanced epithelial ovarian, fallopian tube, and peritoneal cancer.