**Patient Selection for Ovarian Cancer Debulking Surgery** Patient Selection for Ovarian Cancer Debulking Surgery

DOI: 10.5772/intechopen.71585

#### Janos Balega Janos Balega

[43] Davies S. Department of H. Chief Medical Officer. Annual Report 2014: Women's Health. [Internet]. 2014 [cited 2018 Aug 7]. Available from: https://assets.publishing.service.gov.uk/ government/uploads/system/uploads/attachment\_data/file/595439/CMO\_annual\_report\_

[44] Vincent C, Taylor-Adams S, Stanhope N. Framework for analysing risk and safety in clinical

[45] Vincent C. Understanding and responding to adverse events. The New England Journal of

[46] Querleu D, Planchamp F, Chiva L, Fotopoulou C, Barton D, Cibula D, et al. European society of gynaecologic oncology quality indicators for advanced ovarian cancer surgery.

[47] Cowan RA, O'Cearbhaill RE, Gardner GJ, Levine DA, Roche KL, Sonoda Y, et al. Is it time to centralize ovarian cancer care in the United States? Annals of Surgical Oncology. 2016;

[48] Moore AM, Carter NH, Wagner JP, Filipi CJ, Chen DC. Web-based video assessments of operative performance for remote telementoring. Surgical Technology International. 2017;

[49] Moore MD, Abelson JS, O'Mahoney P, Bagautdinov I, Yeo H, Watkins AC. Using GoPro to give video-assisted operative feedback for surgery residents: A feasibility and utility

[50] Keek SA, Leijenaar RT, Jochems A, Woodruff HC. A review on radiomics and the future of theranostics for patient selection in precision medicine. The British Journal of Radiology.

[51] van Driel WJ, Koole SN, Sikorska K, Schagen van Leeuwen JH, Schreuder HWR, Hermans RHM, et al. Hyperthermic intraperitoneal chemotherapy in ovarian cancer. The New

International Journal of Gynecological Cancer. 2016;26(7):1354-1363

assessment. Journal of Surgical Education. 2018;75(2):497-502

England Journal of Medicine. 2018;378(3):230-240

2014.pdf

23(3):989-993

2018; 20170926

30:25-30

medicine. BMJ. 1998;316(7138):1154-1157

Medicine. 2003;348(11):1051-1056

248 Ovarian Cancer - From Pathogenesis to Treatment

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.71585 Additional information is available at the end of the chapter

#### Abstract

Complete surgical cytoreduction is the most important adverse prognostic factor for survival in ovarian cancer. To achieve this, surgeons often have to perform radical and ultraradical procedures with associated significant postoperative morbidity and mortality. Adverse events are most pronounced in patients with borderline or suboptimal capacity to withstand the stress related to surgery. In frail, elderly, malnourished patients, surgeons face limitations to exercise maximum surgical effort; therefore, alternative treatment strategies are required. Neoadjuvant chemotherapy offers a safe and effective way to enhance recovery after delayed debulking surgery in patients who are not optimal candidates for primary debulking surgery.

Keywords: debulking surgery, ovarian cancer, neoadjuvant chemotherapy, nutrition, age

## 1. Introduction

Primary debulking or cytoreductive surgery followed by adjuvant chemotherapy has long been the mainstay of treatment for patients with advanced ovarian cancer. The goal of surgery is complete cytoreduction with no visible residual cancer as it is associated with better survival compared with residuals 0–1 cm or >1 cm [1–6]. During the past two decades, new surgical techniques were incorporated into the armamentarium of gynecologic oncologists to address disease located in the upper abdomen. Such paradigm shift in surgical philosophy has resulted in higher rate of complete cytoreduction, and this has translated into survival benefit [7]. Upper abdominal resection (the so-called ultraradical debulking) should only be performed if complete cytoreduction is achievable as even the presence of minimal residual disease will adversely affect the survival of patients [8].

For long, upfront surgery had been the standard approach for patients with advanced ovarian cancer; however, a new treatment strategy using neoadjuvant chemotherapy followed by delayed primary surgery has emerged two decades ago and been supported by retrospective

© The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and eproduction in any medium, provided the original work is properly cited.

studies [9–11]. However, Bristow et al. in their meta-analysis demonstrated inferior outcomes for patients undergoing neoadjuvant chemotherapy, although this analysis was heavily biased by the retrospective nature of the studies included [12].

surgery, bearing in mind that the use of preoperative laparoscopy to select out unresectable cases was not permitted in the study protocol. Severe complications developed in 5% of the patients in the neoadjuvant chemotherapy arm vs. 15% of the patients in the upfront surgery arm. Survival data for both studies are awaited to confirm superiority of neoadjuvant chemo-

Patient Selection for Ovarian Cancer Debulking Surgery http://dx.doi.org/10.5772/intechopen.71585 251

Despite all criticism, clinical uptake of neoadjuvant chemotherapy has increased worldwide; in the USA, it has increased from 9% in 2003 to 23% in 2013 [19]. Recently, in their joint clinical practice guideline, the Society of Gynecologic Oncology and the American Society of Clinical Oncology have promoted a more selective approach for patients with advanced ovarian cancer, recommending upfront surgery or neoadjuvant chemotherapy for patients with differ-

In clinical practice, upfront surgery and neoadjuvant chemotherapy are not equivalent alternatives for all patients. The aim of this review is to aid the readers to find the most appropriate way to treat their patients by analyzing the factors affecting clinical outcome in ovarian cancer.

There are numerous clinicopathological factors influencing the outcome of ovarian cancer patients:

• Cancer-related factors: grade, stage, tumor extent and size, platinum resistance, molecu-

• Treatment-related factors: residual cancer after surgery, time from surgery to chemother-

• Institutional factors: surgical philosophy and skills, available resources, availability of

Age is an independent prognostic factor for survival for patients with advanced ovarian cancer, but age itself also has an impact on patients' ability to cope with stress related to major surgical interventions [22]. The reserves of the cardiovascular, renal, pulmonary, central nervous, and skeletomuscular systems progressively decline in the elderly, and their physiological response to stress is different. Due to altered physiology of the elderly, the pharmacokinetics

Mahdi et al. in their review of postoperative outcome of ovarian cancer patients found that patients older than 70 but particularly those over 80 years of age more frequently developed chronic kidney failure, cardiorespiratory diseases, and neurological deficit [23]. Compared with patients <60 years of age, the odds ratio for 30-day mortality after surgery was 3.7, 3.1, and 9.3, for patient aged 60–69, 70–79, and ≥80, respectively. While 1% of the patients younger

and pharmacodynamics of medications especially anesthetics are altered.

• Patient-related factors: age, performance status, comorbidities, nutritional status

therapy for the patient cohorts represented in the study.

2. Selecting the right patient for the right treatment

ent clinical characteristics [20, 21].

lar subtype

2.1. Age

apy, complications during treatment

multidisciplinary team

In 2010, Vergote et al. published a prospective, randomized, multi-institutional study on neoadjuvant chemotherapy followed by delayed primary surgery vs. upfront surgery followed by adjuvant chemotherapy. Although the study was heavily criticized by proponents of upfront surgery, it supported a new treatment paradigm by demonstrating equivalent survival with significantly reduced morbidity and mortality for patients undergoing neoadjuvant chemotherapy followed by delayed primary surgery [2]. Kehoe et al. in their prospective, randomized CHORUS trial corroborated these findings [4].

Since the publication of these trials, professional debate has been going on whether to offer primary surgery or neoadjuvant chemotherapy for patients with advanced ovarian cancer and what is the appropriate rate of upfront surgery in cancer centers [13–15]. There has been an apparent dichotomy between highly specialized, quaternary referral centers and smaller units with lower surgical volume and less generous resources. Unfortunately, most cancer centers fail to publish their denominator data, i.e., their referral pathways, the background ovarian cancer population of their catchment area, and the percentage of patients not taken to theater or not receiving any treatment, which brings a significant selection bias into these publications and scientific debates. This makes both the interpretation of the published data and their extrapolation to day-to-day practice difficult [16].

Both EORTC55971 and CHORUS trials have received extensive criticism. Indeed, significant recruitment bias was observed in both studies: patients with large tumor load, unresectable disease, and poor performance status were overrepresented in these studies, and, therefore, many clinicians have been reluctant to extrapolate the results into clinical practice. Furthermore, the rate of complete/optimal resection in these studies was low; in the EORTC55971 trial, <1 cm residual cancer was achieved in only 41.6% of the patients in the upfront surgery arm. Although it improved to 80.7% in the neoadjuvant chemotherapy arm, this surprisingly did not translate into survival benefit [2]. The CHORUS trial reported similar results at 41 and 73%, with no therapeutic advantage associated with such increase [4].

In view of this criticism, the survival results of two subsequent randomized trials, the SCOR-PION study from Italy and the JCOG0602 study from Japan, are highly awaited [17, 18]. Both studies confirmed significantly reduced morbidity and mortality associated with delayed primary surgery following neoadjuvant chemotherapy compared with upfront debulking surgery. In the Italian study, 91 and 90.4% of the patients with large-volume stage 3C and 4 ovarian cancer had <1 cm residual disease after surgery, in the upfront surgery and neoadjuvant chemotherapy arms, respectively. In the upfront surgery arm, 53% of the patients developed major postoperative complications compared with 6% of the neoadjuvant chemotherapy arm.

In the Japanese trial, 37% of the patients with primary debulking achieved residual disease <1 cm and 82% of those undergoing delayed surgery after neoadjuvant chemotherapy. Interestingly, one-third of the patients in the upfront surgery arm received an interval debulking surgery, bearing in mind that the use of preoperative laparoscopy to select out unresectable cases was not permitted in the study protocol. Severe complications developed in 5% of the patients in the neoadjuvant chemotherapy arm vs. 15% of the patients in the upfront surgery arm. Survival data for both studies are awaited to confirm superiority of neoadjuvant chemotherapy for the patient cohorts represented in the study.

Despite all criticism, clinical uptake of neoadjuvant chemotherapy has increased worldwide; in the USA, it has increased from 9% in 2003 to 23% in 2013 [19]. Recently, in their joint clinical practice guideline, the Society of Gynecologic Oncology and the American Society of Clinical Oncology have promoted a more selective approach for patients with advanced ovarian cancer, recommending upfront surgery or neoadjuvant chemotherapy for patients with different clinical characteristics [20, 21].

In clinical practice, upfront surgery and neoadjuvant chemotherapy are not equivalent alternatives for all patients. The aim of this review is to aid the readers to find the most appropriate way to treat their patients by analyzing the factors affecting clinical outcome in ovarian cancer.
