Endometrial and ovarian cancer

Uterine anatomy and tumor origins Uterine cancer: Endometrium: endometrial carcinoma (type I and II) Myometrium: uterine sarcoma Cervical cancer: Cervix: squamous cell carcinoma and rarely adenocarcinoma of the cervix

Epidemiology of uterine cancer

Epidemiology of endometrial cancer The most common uterine cancer Approximately 75% of patients are menopausal

2 main categories of endometrial cancer Endometrial cancer is divided into type I and type II, characterized by distinct biologic and clinical behavior, with different causes Type I carcinomas account for approximately 85% of all EC and are associated with a hyperestrogenic state and generally are low- grade; histology: endometrioid carcinoma. Patients are usually younger (65). Type II tumors are estrogen-independent and arise in the setting of uterine atrophy and generally consist of poorly differentiated tumors; histology: papillary serous carcinoma, clear cell carcinoma and malignant mixed müllerian tumor. They represent approximately 15% of all ECs. Type II patients are more often multiparous, older (70), and less likely to be obese. More frequent in blacks than whites. Molecular genetic studies over the past decade have shown that the two tumor types evolve via distinct pathogenetic pathways

Risk factors For endometrioid uterine cancer the most important risk factor is unbalanced or high estrogen levels Obesity is an important contributing factor, since fatty tissue produces estrone (E1). (These patients usually have metabolic syndrome.) Estrone is unbalanced by progesterone, since the ovaries don’t produce enough progesterone in menopausal or premenopausal women=> the endometrial mucosa is always in the proliferative stage=>hyperplasia->atypical hyperplasia -> cancer

Risk factors Late menopause (>52 yrs) Hormone replacement therapy with estrogen only Similarly, Tamoxifen, used in the treatment of breast cancer can cause endometrioid uterine cancer, since it is an agonist on the uterine mucosa (and antagonist on breast tissue)

Genetic risk factors hereditary nonpolyposis colorectal cancer syndrome (HNPCC) or Lynch syndrome II

Reminder: Metabolic Syndrome The metabolic syndrome is characterized by a group of metabolic risk factors in one person. They include: Abdominal obesity (excessive fat tissue in and around the abdomen) Atherogenic dyslipidemia (high triglycerides, low HDL cholesterol and high LDL cholesterol — that foster plaque buildups in artery walls) HBP Insulin resistance or glucose intolerance Prothrombotic state (e.g., high fibrinogen or plasminogen activator inhibitor–1 in the blood) Proinflammatory state (e.g., elevated C-reactive protein in the blood)

Routes of extension-Local spread myometrium, cervix, vagina, parametria, bladder, rectum, ovaries

Lymphatic spread Lymphatic spread (regional lymph nodes): -tumors in the uterine fundus->directly to paraaortic lymph nodes -tumors from the middle and lower part of the uterus->internal and external iliac lymph nodes->paraaortic lymph nodes or to inguinal lymph nodes

Routes of extension Peritoneal Distant Metastases: -lung, liver, bone

Symptoms of endometrial cancer Uterine bleeding or discharge Metrorrhagia in menopause is probably endometrial cancer, unless proven otherwise. (can be cervical cancer to) -this symptom is early=> the majority of cases (70%) will be diagnosed with stage I disease confined to the corpus, and these patients have excellent survival Other symptoms due to compression to adjacent organs or invasion (invasion of the parametria: ureteral obstruction)

Diagnosis of endometrial cancer Gynecologic examination: -bimanual examination: uterus has increased volume -rectal examination: extension to the parametria -speculum examination: the cervix is usually normal; it can detect cervical or vaginal invasion

Reminder-Pelvic exam Step One–External Genital Exam Purpose: Check for irritation, unusual discharge, cysts or genital warts and to make sure the glands around the opening of vagina or urethra are not swollen or inflamed. How it's Done: The area is both visually and manually examined. Step Two–Internal Bimanual Exam Purpose: Evaluate the size, shape and position of pelvic organs (uterus, ovaries and fallopian tubes) and help detect abnormalities such as adhesions, tears, enlargements, cysts, tumors or tenderness. How it's Done: One or two gloved, lubricated fingers are placed in the vagina while pressing on the lower abdomen with the other hand. Step Three–Internal Rectovaginal Exam Purpose: Evaluate the tissue in between the uterus and vagina and the ligaments that hold the uterus in place. Check for rectal bleeding. How it's Done: A gloved, lubricated finger is placed in the vagina and another in the rectum while pressing on the lower abdomen. Step Four–Internal Speculum Exam Purpose: Examine vaginal walls and cervix for damage, sores, growths, inflammation or unusual discharge. A Pap smear might be taken during this phase of the exam. How it's Done: A speculum is gently inserted and opened to hold the walls of the vagina apart.

Diagnosis of endometrial cancer Endometrial biopsy (outpatient); If biopsy not diagnostic => Dilation and curettage=D&C (inpatient)

The establishment of the extension and general work-up For all patients: chest radiography, CBC, platelets, renal function 1.Tumor limited to the uterus=> additional tests needed for surgery -then the patient is operated and the disease surgically staged 2. Suspected or proven extrauterine disease => CT/MRI of the pelvis + abdomen, +/- cystoscopy, +/- rectoscopy if suspicion of mucosal invasion

Treatment of endometrial cancer Tumor limited to the uterus and no cervical involvement a)Medically operable=> total hysterectomy and bilateral salpingo-oophorectomy (TH+BSHO) plus pelvic and para-aortic lymphadenectomy b)Medically inoperable=> radiotherapy

Treatment of endometrial cancer Extrauterine disease a)Preoperative radiotherapy followed by surgery b)Radiotherapy alone

Treatment of endometrial cancer In the presence of risk factors adjuvant radiotherapy might be used after surgery

Non-malignant tumors: fibroids

Questions What are the symptoms of endometrial cancer and at which age group is the most common? How is the diagnosis of endometrial cancer made?

Ovarian cancer The most lethal cancer from the tumors of the female genitalia, because diagnosis is usually late and spread occurs easily to the peritoneum

Risk factors I.Genetic: -BRCA1/2 -Lynch 2 syndrome etc. II. Reproductive -early menarche -late menopause -nulliparity Protective: oral contraceptives III. Environmental -obesity -”industrialized” living

Histology 1.Epithelial tumors (90%) -most frequent subtype: serous adenocarcinoma 2. Stromal tumors 3. Germinal tumors

Routes of spread Peritoneal Greater omentum

Routes of spread Invasion of adjacent structures (uterine corpus, salpinx) Lymphatic: iliac and para-aortic lymph nodes Hematogenous: liver

Symptoms Abdominal: abdominal pain, dyspepsia, bloating, increase in the perimeter of the abdomen Pelvic: metrorrhagia, pollakiuria Thoracic: dyspnea (due to ascites or pleurisy) General: fatigue, weight loss

Diagnosis Pelvic exam US or CT of the pelvis and abdomen CA-125 tumor marker Chest radiography additional tests needed for surgery

Treatment SURGERY +/- CHEMOTHERAPY In some stage I patient: unilateral salpingo- oophorectomy for fertility preservation All other patients: “optimal debulking”=“optimal cytoreduction” =resection of all tumor tissue, if possible, or leaving behind tumor tissue with a diameter of less than 1 cm

Surgery has to include: total hysterectomy and bilateral salpingo- oophorectomy (TH+BSHO) plus pelvic and para-aortic lymphadenectomy Omentectomy Resection of the peritoneal metastases, if present Resection of involved organs

Adjuvant chemotherapy Intraperitoneal + IV IV only

Questions? What is the special kind of surgery done in locally advanced ovarian cancer?