CONSERVATIVE SURGERY OF OVARIAN CANCER

Guided by:Dr. Sp.OG

By:Dr.

PPDS 1 Obstetry and GynaecologyMedical Faculty of Sebelas Maret University / dr. Moewardi Hospital Surakarta2015

CHAPTER IINTRODUCTION

Ovarian cancer is diagnosed in nearly a quarter of a million women globally each year. It is the eighth most common cancer in women and the seventh leading cause of cancer death among women, responsible for approximately 140,000 deaths each year. It has the highest mortality rate of all gynaecological cancers. The prognosis for ovarian cancer patients is poor, particularly when the disease is diagnosed in its later stages. Symptoms are ambiguous and often misdiagnosed so the majority of patients are only identifed in the advanced stages of the disease. Ovarian cancer is therefore often referred to as The Silent Killer. The current standard of care for ovarian cancer - surgery and chemotherapy - has remained unchanged for many years and the 5-year US survival rate has improved by only 9% since 1975. Statistics show that just 45% of women with ovarian cancer are likely to survive for fve years compared to up to 89% of women with breast cancer. In most cases front-line treatment (with surgery and chemotherapy) does not stop the disease returning. Most women with advanced ovarian cancer will have a relapse following initial treatment, usually within 15 months of initial diagnosis. There is a real need for new, more effective treatment options for women with ovarian cancer. This guide provides an overview of ovarian cancer, including its incidence, risk factors, symptoms, diagnosis and treatment options.1Ovarian cancer is the seventh most common cancer diagnosis among womenworldwide, and the fthmost common cancer diagnosis among women in higher-resource regions. The world rate is estimated to be 6.3 per 100 000 women, and is highest in highresource countries (9.3 per 100 000 women). Primary peritoneal cancer and primary fallopian tube cancer are rare malignancies but share many similarities with ovarian cancer. Clinically, these 3 cancers are managed in a similar manner. The main purpose of staging systems is 2-fold: to provide standard terminology that allows comparison of patients between centers; and to assign patients and their tumors to prognostic groups requiring specic treatments. Cancer staging evolves continuously as scientic developments occur, diagnostic methods improve, and more accurate prognostic information becomes available. Over the past quarter of a century, several scientic developments have challenged traditional concepts in ovarian cancer. Initially, it was recognized that ovarian cancer is not a homogeneous disease, but rather a group of diseaseseach with different morphology and biological behavior. Approximately 90% of ovarian cancers are carcinomas (malignant epithelial tumors) and, based on histopathology, immunohistochemistry, and molecular genetic analysis, at least 5 main types are currently distinguished: high-grade serous carcinoma (HGSC [70%]); endometrioid carcinoma (EC [10%]); clear-cell carcinoma (CCC [10%]); mucinous carcinoma (MC [3%]); and low-grade serous carcinoma (LGSC [b5%]).These tumor types (which account for 98% of ovarian carcinomas) can be reproducibly diagnosed by light microscopy and are inherently different diseases, as indicated by differences in epidemiologic and genetic risk factors; precursor lesions; patterns of spread; and molecular events during oncogenesis, response to chemotherapy, and prognosis. Much less common are malignant germ cell tumors (dysgerminomas, yolk sac tumors, and immature teratomas [3% of ovarian cancers]) and potentially malignant sex cord-stromal tumors (1%2%, mainly granulosa cell tumors). The biomarker expression prole within a given histotype is consistent across stages. Ovarian cancers differ primarily based on histologic type.2Despite great efforts in developing novel screening, diagnosis and therapeutic strategies, the incidence and mortality of ovarian cancer have not significantly changed in the last 30 years. It remains the leading cause of death from gynecologic malignancy with a lifetime probability of developing the disease of 1 in 59. Worldwide, approximately 200.000 women are annually diagnosed with ovarian cancer, and almost 70% of them will be diagnosed at advanced stage disease. With current treatment modalities, the 5-year survival rate ranges from 8095% for those with organ-confined or early stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage I-II); to 30 40% for those women with advanced disease, FIGO stage III-IV. Thus, ovarian cancer is a challenging and complex malignancy.Surgical management of ovarian cancer remains as the cornerstone treatment of this disease. An adequate full surgical staging in women with early stage disease has demonstrated to improve oncologic outcome. On the other hand, complete surgical cytoreduction is the only modifiable prognosis factor for patients with advanced disease. This chapter will describe the rationale and surgical steps for an adequate surgical staging for women with early stage ovarian cancer, and for obtaining the maximal surgical cytoreduction in women affected by advanced stage and relapsed disease.3The standard treatment of ovarian cancer includes upfront surgery with intent to accurately diagnose and stage the disease and to perform maximal cytoreduction, followed by chemotherapy in most cases. Surgical staging of ovarian cancer traditionally has included exploratory laparotomy with peritonealwashings, hysterectomy, salpingo-oophorectomy, omentectomy, multiple peritoneal biopsies, and possible pelvic and para-aortic lymphadenectomy. In the early 1990s, pioneers in laparoscopic surgery used minimally invasive techniques to treat gynecologic cancers, including laparoscopic staging of early ovarian cancer and primary and secondary cytoreduction in advanced and recurrent disease in selected cases. Since then, the role of minimally invasive surgery in gynecologic oncology has been continually expanding, and today advanced laparoscopic and robotic-assisted laparoscopic techniques are used to evaluate and treat cervical and endometrial cancer. However, the important ques-tion about the place of the minimally invasive approach in surgical treatment of ovarian cancer remains to be evaluated and answered.4Conservative and functional surgery is increasingly used in surgical oncology, the aim being to preserve the function of organs and to reduce radical resection. The development of new surgical procedures in oncological gynaecological surgery is a perfect example of this evolution. Although radical surgery remains the `gold standard' in the treatment of ovarian and cervical cancer, a conservative approach can be considered in patients with early-stage disease, in order to preserve their fertility function. These procedures were proposed in selected patients, depending on histological sub-types and prognostic factors. Ovarian cancers are classified as epithelial and non-epithelial tumours. Conservative treatment of non-epithelial ovarian tumours, particularly germ cell tumours, has been considered for some time as a standard surgery in young patients (Creasman et al., 1979; Schwartz, 1984; Brewer et al., 1999). Published data relating to conservative surgery in borderline and invasive epithelial ovarian cancer are more recent however.5

CHAPTER IISURGICAL STAGING OF OVARIAN CANCER2,8,9,10

Approximately 25% of newly diagnosed ovarian cancer will be early stage disease. Prognosis is good with survival rates ranging from 80 % to 95 % when recommended treatment is followed. These patients are initially managed by comprehensive surgical staging, which is relevant not only for identifying women with truly early stage disease, but also to select patients who will be candidates for adjuvant chemotherapy.

Adequate surgical staging procedures include: exploration of abdomen/pelvis, peritoneal washings, bilateral salpingo-oophorectomy, hysterectomy, peritoneal biopsies of Cul-de-sac, pelvic walls, paracolic gutters, diaphragm, suspicious areas, omentectomy, appendectomy, as well as pelvic and para-aortic node dissection up to the renal veins. (TABLE 1). These procedures are needed to find hidden disease in nearly 18% of women, which has implications in the prognosis and subsequent patient treatment. Surgeon expertise is crucial given that it was correlated with under-staged ovarian cancer. Several studies demonstrated that over 30% of patients operated by general gynecologists or general surgeons were upstaged by gynecologist oncologists by finding disease on pelvic-aortic lymph nodes, diaphragm biopsies and omentum. Moreover, as it has been demonstrated, inadequate initial surgical staging leads to a higher risk of developing recurrent disease despite receiving adjuvant chemotherapy. Thus, if the operative risk is not too high, all patients should be routinely re-staged before starting chemotherapy.

Table . Surgical staging procedures for early stage ovarian cancer

Surgical staging proceduresMidline vertical incision is the recommended surgical approach for initial management of suspected early stage ovarian cancer. The incision is firstly made from the pubis to the umbilicus and then progressed to xifoid appendix, if surgical staging is indicated following the frozen section diagnosis. The abdominal-pelvic cavity is opened and visualized. If free fluid is present, a minimum sample of 100 cc should be obtained for cytological examination. Peritoneal washing from paracolic gutters, pelvis and abdominal cavity should be done in the absence of ascites. It is estimated that over 30% of patients with stage I disease have tumoral cells on cytological examination. Careful inspection and palpation is preformed to detect extra-ovarian implants in a systematic way: starting by right paracolic space, advancing the hand to the right kidney, suprahepatic space, the right diaphragm, right hepatic lobe, gallbladder, Morrisons pouch, left hemi-diaphragm, left hepatic lobe, spleen, stomach, transverse colon, left kidney and left paracolic space. The lesser sac is entered on the left side of the gastrocolic ligament. Both surfaces of the mesentery should be examined and retroperitoneal vascular areas should be palpated as well. The result of this comprehensive procedure should be properly described.The ovaries need to be examined for capsule rupture or external excrescences. The affected ovary must then be removed for frozen section. Although the influence on the prognosis of the intraoperative rupture of malignant ovarian tumors is controversial,[12] adnexal masses should be removed intact. If malignancy is confirmed in the frozen section, full surgical staging, as previously described, must be performed by the extension of the incision up to xifoid appendix. Contralateral oophorectomy and total hysterectomy is completed due to the possibility of synchronous cancer.Even though controversial, random peritoneal biopsies are indicated in early-stage disease. A retrospective study demonstrated that less than 4% of patients with ovarian cancer were upstaged due to positive peritoneal biopsies. No patient, however, had a change in treatment recommendations based on these biopsies.[13] Infracolic omentectomy should be performed from the hepatic to splenic flexure. During dissection, the lesser sac is developed dissecting the posterior and anterior layer of the transverse mesocolon, while preserving the middle colic artery. The omentum is removed and the pedicles are sequentially sutured ligated. Appendectomy is only reserved for mucinous histology.

Retropetitoneal lymph node dissectionThe incidence of lymph-node involvement in patients with disease confined to the ovary is 5% in only pelvic nodes, 9% in aortic nodes and 6% in both pelvic and aortic nodes. Systematic lymphadenectomy as part of surgical staging of apparent early stage ovarian cancer is associated with a statistically significant increase in median operative time, median blood loss, and the proportion of patients undergoing blood transfusions. Systematic lymphadenectomy, however, significantly improves progression-free survival (PFS) rates, without a statistically significant impact on overall survival (OS). Lymphatic drainage of the ovaries is known to follow the gonadal blood supply that reaches the renal vein, on the left side, and the inferior vena cava, on the right side. Pelvic lymphadenectomy should include removal of nodes from paravesical and pararectal spaces, including bilateral common iliac nodes. Aortic nodes should be removed from aortic bifurcation to the renal veins.

Minimally invasive surgery for surgical staging ovarian cancerOver the last years, laparoscopy has gained an important role for the management of suspected adnexal masses. High-volume centers have reported their experience in performing a comprehensive surgical staging by using minimally invasive surgery. Nezhat et al.reported a case series of 36 patients with early stage invasive ovarian carcinoma managed bylaparoscopy. They showed 100% OS rate with a mean duration of follow-up of 55.9 months.Chi et al. conducted a case control study by staging 20 patients with early ovarian cancer with laparoscopy compared with 30 patients staged with laparotomy. There were no differences in the omental specimen size or number of lymph nodes removed. Blood loss and hospital stay were lower for the laparoscopy group, with longer operating time. There were no conversions to laparotomy or other intraoperative complications in the laparoscopy group.Despite laparoscopic staging of early ovarian cancer seems to be a safe and feasible procedure performed by expert surgeons, the possibility of cyst rupture or port-site metastases remain controversial. The immediate effect of tumor rupture is that a patient with a potentially curable disease will require additional adjuvant chemotherapy. Preoperative evaluation is essential, as well as the surgical experience and the quality of laparoscopic instruments. Even though there are no specific recommendations, adnexal masses up to 5-6 cm could be reasonably managed by laparoscopy. The etiology of port-site metastases is uncertain. Several hypotheses include tumor cell entrapment, direct spread from the trocar in which instruments are exchanged, and the chimney effect, which suggests that tumor cells travel along the sheath of the trocars with the leaking gas. Port-site metastases have been reported in 1% to 2% of patients with ovarian cancer. However,