Ovarian Cancer in Obese Women: Risk and Optimal Medical and Surgical Treatment Options

Worldwide, over 230,000 women are diagnosed with ovarian cancer each year, and about 140,000 women die from this disease. In the USA, there will be an estimated 21,290 new cases, and 14,180 deaths from ovarian cancer in 2015 [1]. It is a fatal disease with about 40% 5-year survival [2]. This poor survival is because 75% of all cases of this disease in developed countries are diagnosed with metastasis outside the pelvis [3]. It is worth noting that obesity is a significant health concern in the USA, with an increasing incidence over the last decade. Over 30% of US adults 20 years of age and older are obese, and 65% of adults are considered overweight based on their BMI [4]. Stage of disease at diagnosis, age, tumor grade and the amount of residual disease following surgery predict the survival time [5]. Obesity has been shown to be associated with poorer survival in a number of cancers including breast [6], prostate [7] and colorectal cancer [8]. Women who are obese may have more aggressive tumors, as excessive deposition of adipose tissue leads to the upregulation of cellular proliferation pathways which may enhance tumor growth and metastasis [9]. Lexg65ptin is a 16-kDa protein encoded by the ob gene, and is produced by white adipose tissue. It acts as a growth factor in a number of cancer cell lines including breast, endometrial and prostate cancers [10]. Leptin has been shown in a colon cancer cell line to activate MAPK and NF-κB pathways. This activity led to apoptosis resistance after the addition of sodium butyrate [11]. Unbound (free) IGF1 is more highly expressed in obese individuals than their normal weight counterparts [12], and has itself been shown to correlate with increased breast cancer risk in women. IGFBP-2, a binding protein for IGF, also seems to promote invasion in ovarian cancer [13]. It was observed that obesity is differentially associated with ovarian cancer in premenopausal and postmenopausal women and with different histologic subtypes of cancer [14]. Several studies suggest that obesity is a poor prognostic factor for ovarian cancer survival. In a study of over 495,000 prospectively followed healthy women, there was a significantly increased ovarian cancer mortality among obese women when compared with ideal bodyweight study participants (relative risk: 1.26 for BMI >30) [15]. The correlation of increased patient BMI with decreased disease-free survival and overall survival is probably due to the biologic effect of obesity in tumor growth, apoptosis or chemotherapy resistance pathways. It was noted that obesity is associated with increased insulin levels, which results in increases in IGF-1 [16]. High levels of IGF-1 have been associated with ovarian cancer in women younger than 55 years of age [17]. In 2005, the US FDA approved the da Vinci Surgical System (Intuitive Surgical) for gynecologic surgery. Since then, robotic-assisted gynecologic surgery has increased. This approach can be a safe and effective method in select morbidly obese patients, allowing them the opportunity to undergo minimally invasive surgery without the adverse surgical outcome. The high-definition 3D vision system and retracting capability of the third robotic arm are of notable advantages over laparoscopic surgery. The use of an EndoPaddle (Covidien, Mansfield, MA, USA) to retract the omentum is recommended in obese patients undergoing robotic surgery for ovarian and endometrial cancer. It was shown that single port access, high definition and double consol robot-assisted laparoscopic supraradical cytoreductive and panniculectomy surgery in morbidly obese women with advanced ovarian cancer are well tolerated, feasible and associated with acceptable morbidity. It provided satisfactory surgical and oncologic outcome [18]. Observational studies have shown that chemotherapy dose intensity [19] and its cumulative dose may be lower in obese patients compared with normal weight. It was noted that obese patients with ovarian cancer who have their doses capped at 2.0 m² experience similar or lower rates of chemotherapy-induced toxicities compared with those who were dosed according to their bodyweight; this indicates that obese patients may be receiving suboptimal treatment, and therefore may be at an increased risk of disease progression and reduced survival [20]. In addition, obesity is commonly associated with other comorbidities such as diabetes and cardiovascular disease, which may also lead to patients being treated with reduced doses of chemotherapy [21]. To conclude, obesity is common in ovarian cancer patients, obese patients are more likely to receive underdosing and a reduced dose intensity, and commonly results in lower chemotherapy dosing than recommended. Robot-assisted laparoscopic surgery is an ideal surgical technique for obese women with ovarian cancer.