Identification of patient groups at highest risk from traditional approach to ovarian cancer treatment
Research Highlights
► Most patients with ovarian cancer benefit from aggressive surgery. ► We identified a subgroup of patients in whom an alternative approach may be the better strategy. ► Different subgroups of patients might benefit from different approaches.
Introduction
Standard recommendations for patients with advanced ovarian cancer (AOC) include surgical cytoreduction followed by platinum-based adjuvant chemotherapy [1]. The rationale for surgical cytoreduction finds its first evidence in 1975 with a publication by Griffith [2]. Subsequently, several publications confirmed the role for primary cytoreductive surgery in management of ovarian cancer [3], [4], [5], [6], [7], [8], [9]. Countering this thinking is the concept of the importance of intrinsic tumor behavior which cannot be completely overcome with surgical resection [10], [11], [12], [13]. While undoubtedly initial stage remains an important independent variable, cytoreduction appears to improve survival regardless independent of stage [13], [14]. It is widely recognized that patients with stage IIIC disease and carcinomatosis, or widely disseminated peritoneal disease, carry a worse prognosis than patients without it [6]. But we and others have also shown that surgical cytoreduction can improve survival to equal those with less initial disease volume [5], [6], [14]. However, some patients are poor candidates for aggressive surgical procedures and might be better served by an alternative approach.
An important challenge if we are to maximize overall outcomes for our patients is to better identify the subgroups of patients who are unlikely to benefit from an aggressive surgical approach, thus avoiding unnecessary morbidity and short term mortality which dramatically impact and shorten remaining life of these women and dramatically raise cost of care. This is particularly cogent as many oncologists are employing a neoadjuvant approach which has not been directly compared to aggressive primary surgery. Careful analysis of outcomes can help in the selection of most appropriate candidates for non-standard therapy. We previously demonstrated that age, low pre-operative levels of albumin, poor performance standard were all predictors of postoperative morbidity [15]. Others have recently shown the predictive value of complexity of the surgery and impaired performance status along with obesity and elevated SGOT to be predictors of perioperative morbidity [16]. Thus, the primary question we tried to answer was whether we could identify a subgroup of patients with particularly high risk, unlikely to tolerate complex surgery in a multi-center model to reduce institutional bias. Ultimately, we were able to identify three predictors (age, poor performance or nutritional status, and disseminated disease) that, combined together, constituted a small, but very “high risk group” of patients in which aggressive surgical efforts do not translate into improved survival and are associated with significant negative impact.
Section snippets
Patients and methods
Institutional Review Board approval was obtained at all participating institutions for this study.
Patients' characteristics
A total of 576 patients diagnosed with AOC were included in the study. One hundred and ninety-nine patients (35%) were enrolled from Mayo Clinic, 138 patients (24%) from Johns Hopkins Medical Center, 82 (14%) patients from the UCLA system, and 157 (27%) from Memorial Sloan Kettering Cancer Center. Most of the patients (N = 474, 82.4%) had serous histology. Considering tumor dissemination at the beginning of the surgical procedure, 95 patients (16.8%) had low tumor dissemination (LTD), 242 (42.9%)
Discussion
The primary goal of cytoreduction has progressively moved from the removal of all the disease larger than 2 cm, to the removal of all the visible disease. Several studies have in fact suggested that complete cytoreduction, as opposed to so-called optimal, has the greatest impact on survival in patients with advanced ovarian cancer [6], [7], [8], [9]. Unfortunately, no preoperative test is able to predict which patient can be completely debulked, though many have been tested [18], [19], [20], [21]
Conflict of interest statement
The authors declare that there are no conflicts of interest.
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