Malignant Ovarian Tumor A.Alsaadoun (2/12/2008) Saturday, April 22, 2017 Malignant Ovarian Tumor Dr. Mashael Shebaili Assistant Prof. & Consultant Department OF Ob & Gyn. King Saud University

Objectives introduction History and examination Risk factor screening Epidemiology screening Investigation Treatment Prevention

Introduction Historically ovarian cancer has been called the silent killer because symptoms often become apparent too late in the processes that the chance of cure were poor

Ovarian cancer accounts for 3.3% of all new cases of cancer Epidemology The lifetime risk for developing ovarian cancer is 1.6% in the general population Ovarian cancer accounts for 3.3% of all new cases of cancer The fifth in cancer deaths among women and accounts for more deaths than any other cancer of the female reproduction system only 19% of ovarian cancers discovered at early stage. Most cases are diagnosed in the seventh decade of life.

symptoms Urinary urgency Abd/pelvic pain Abdominal distention Vaginal bleeding symptoms Bloating Change bowel habit Irregular menses

Types of ovarian cancer Germ cell tumor Epithelial tumor Stromal cell tumor

Physical finding Ascites Patient with advance disease Ovarian or Pelvic mass Pleural effusion Ascites Bowel obstruction

Obesity parity HRT OCP Risk factors Hereditary Family history

Multiple pregnancies offer an increasingly protective effect A.Alsaadoun (2/12/2008) Saturday, April 22, 2017 parity Obesity Women who have been pregnant have 50% decreasd risk for develoing ovarian cancer compared to nulliparous women Multiple pregnancies offer an increasingly protective effect HRT OCP Hereditary Family history 9

Its protective effect lasted to 2-3 decade after cessation of use OCP Obesity The use of OCP more than one year reduce the risk of ovarian cancer by 30%-50% Its protective effect lasted to 2-3 decade after cessation of use Parity HRT Hereditary Family history

No evidence of hereditary pattern Family history Obesity No evidence of hereditary pattern The risk in general popultion is 1.6% The risk increased to 4-5% when 1st degree family member is affected ,rising to 7% when two relatives are affected Parity HRT OCP Hereditary

Hereditary Obesity Represent 5% of all ovarian cancer 2 syndrome are clearly identified: Breast/ovarian cancer syndrome : Associated with early onset breast or ovarian cancer ,transmitted as AD and occur due to BRCA gene mutation Parity HRT OCP Family history

Hereditary Obesity Lynch ll syndrome or hereditary non polyposis colorectal cancer : These families characterized by high risk of developing colorectal ,endometrial, stomach, small bowel, breast ,pancreas and ovarian cancer and it is due to mutation in mismatch repair gene . Parity HRT OCP Family history

HRT Obesity A large study puplished in the journal of national cancer institute in October 2006 report that women who used hormonal therapy for 5 years or more face a significantly increase risk of ovarian cancer Parity OCP Hereditary Family history

Obesity Studies have suggested that women who are obese at age of 18 are at increased risk of developing ovarian cancer befor menopause parity HRT OCP Hereditary Family history

However, 95% of all ovarian cancers occur in women without risk factors.

Screening Effective screening tests are available for several common cancers, including: mammography for breast cancer, the Pap test for cervical cancer but no standardized screening test exists to reliably detect ovarian cancer. Researchers haven't yet found a screening tool that's sensitive enough to detect ovarian cancer in its early stages and specific enough to distinguish ovarian cancer from other, noncancerous conditions

Screening Most experts feel that a screening protocol for ovarian cancer should have a positive predictive value of at least 10 percent (that is, no more than nine healthy women with false-positive screens would undergo unnecessary procedures for each case of ovarian cancer detected

US LPA Screening Other tumor Ca 125 markers A.Alsaadoun (2/12/2008) Saturday, April 22, 2017 Screening US LPA Ca 125 Other tumor markers 19

Has a sensitivity of 70%-80% And a specificity of 98.6% - 99.45% Screening US LPA Ca 125 Other tumor marker Has a sensitivity of 70%-80% And a specificity of 98.6% - 99.45%

abscess, renal disease) and in physiological condition (pregnancy and Screening US LPA Ca 125 Other tumor marker False positive : Increase in other cancers (pancreas ,breast ,bladder ,liver ,lung) ,in benign disease (diverticulitis , endometriosis, benign ovarian cyst ,tuboovarian abscess, renal disease) and in physiological condition (pregnancy and Menstruation )

Elevated in only 80% of ovarian cancer cases Screening US LPA Ca 125 Other tumor marker False negative : Elevated in only 80% of ovarian cancer cases

Positive predictive value: Screening US LPA Ca 125 Other tumor marker Positive predictive value: Annual CA125 testing has low predictive value (3%) which does not meet the level required for screening post meopausal women at average risk

CA125 as a first line test followed by US as a second line test Screening US LPA Ca 125 Other tumor marker CA125 as a first line test followed by US as a second line test for positive CA125 result has a shown to be very specific and achieve positive predictive value of 20% or greater .

Screening of 100,000 women over age of 45,would detect 40 cases of US LPA CA125 Other tumor markers Highly false positive :In one of the study it has been estimated that US Screening of 100,000 women over age of 45,would detect 40 cases of Ovarian cancer with 5,398 false positive result and more than 160 Complications from laproscopy .

In other screening studies in women at high risk of ovarian cancer ,US LPA CA125 Other tumor markers In other screening studies in women at high risk of ovarian cancer ,US has performed poorly in detecting early stage epithelial ovarian cancer .

matrix in ovarian cancer . LPA concentration are elevated in 96% of A.Alsaadoun (2/12/2008) Saturday, April 22, 2017 Screening US LPA CA125 Other tumor markers The lipid lysophosphatidic acid is associated with invasion of the extracellular matrix in ovarian cancer . LPA concentration are elevated in 96% of women with ovarian cancer including 90% of those with stage 1 disease Studies to evaluate the use of this biomarker are ongoing . 27

Screening US LPA CA125 Other tumor marker Studies on CA72-4,macrophage –colony stimulating factor (MCSF)Osbepontin ,inhibin and Kallikrein are going to evalute combination of tumor marker complemantary to CA 125 that could offer greater sensitivity and specificity than CA125 alone .

Benefit VS Harm In one study of women at high risk of ovarian cancer, researchers discovered that use of screening tests led to 20 operations on Women only one of whom was found to have cancer — metastatic breast cancer, not ovarian cancer. The preliminary results from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, appears in the November 15, 2005 American Journal of Obstetrics and Gynecology , Women who had an abnormal test result in one or both screening tests underwent a variety of diagnostic procedures to determine whether cancer was present, including 570 women who underwent a surgical procedure as follow-up. Thus, 541 women underwent surgery but did not have cancer. CD4

Point to remember Screening for ovarian cancer is expensive because of low prevalence of disease, high rate of surgical intervention for noncancerous disease, and high costs of tests and follow-up. Many experts suggest that the possible benefits of lowered mortality or years of life saved do not justify the costs of screening. The low positive predictive value associated with currently available screening modalities suggests that more women without cancer will be subject to laparoscopy or laparotomy than will those with cancer. Modeling studies of annual screening with CA 125, with or without a single screening with transvaginal ultrasound, found an increase in life expectancy of less than one day per woman screened . No definitive large randomized controlled trials have been completed to show whether any screening strategy decreases mortality from ovarian cancer

Screening recommendation No organization currently recommends either ultrasound or cancer marker screening in asymptomatic women, and multiple organizations (including the American College of Physicians, the Canadian Task Force on the Periodic Health Examination, and the American College of Obstetricians and Gynecologists) recommend against it. Regarding women at higher risk (e.g., hereditary cancer syndromes), the NIH consensus conference recommends annual CA 125 measurements, pelvic exam, and transvaginal ultrasound until childbearing is completed; at age 35, women should be referred for bilateral oophorectomy.

Investigation Lab Studies If ovarian cancer due to a pelvic or ovarian mass is suggested, minimize preoperative testing needed and staging laparotomy indicated . Routine preoperative tests include CBC count, chemistry panel (including liver function tests), and a cancer antigen 125 assay (CA-125).

Investigation Imaging Studies Routine imaging is not required in all patients in whom ovarian cancer is highly suggested. If diagnostic uncertainty is present, a pelvic ultrasound or CT scan of the abdomen and pelvis is warranted.

Investigation Other Tests In patients with diffuse carcinomatosis and GI symptoms, a GI tract workup may be indicated, including: Upper and/or lower endoscopy Barium enema Upper GI series Procedures Biopsy A fine-needle aspiration (FNA) or percutaneous biopsy of an adnexal mass is not routinely recommended. In most cases, taking this approach instead of performing a surgical staging laparotomy may only serve to delay appropriate diagnosis and treatment of ovarian cancer. If a clinical suggestion of ovarian cancer is present, the patient should undergo a diagnostic and surgical procedure. An FNA or diagnostic paracentesis should be performed in patients with diffuse carcinomatosis or ascites without an obvious ovarian mass.

staging Ovarian cancer is staged using the International Federation of Gynecology and Obstetrics (FIGO) : Stage I - Growth limited to the ovaries Stage Ia - Growth limited to 1 ovary, no ascites, no tumor on external surface, capsule intact Stage Ib - Growth limited to both ovaries, no ascites, no tumor on external surface, capsule intact Stage Ic - Tumor either stage Ia or Ib but with tumor on surface of one or both ovaries, ruptured capsule, ascites with malignant cells or positive peritoneal washings Stage II - Growth involving one or both ovaries, with pelvic extension Stage IIa - Extension and/or metastases to the uterus or tubes Stage IIb - Extension to other pelvic tissues Stage IIc - Stage IIa or IIb but with tumor on surface of one or both ovaries, ruptured capsule, ascites with malignant cells or positive peritoneal washings Stage III - Tumor involving one or both ovaries, with peritoneal implants outside the pelvis and/or positive retroperitoneal or inguinal nodes; superficial liver metastases equal stage III Stage IIIa - Tumor grossly limited to pelvis, negative lymph nodes but histological proof of microscopic disease on abdominal peritoneal surfaces Stage IIIb - Confirmed implants outside of pelvis in the abdominal peritoneal surface; no implant exceeds 2 cm in diameter and lymph nodes are negative Stage IIIc - Abdominal implants larger than 2 cm in diameter and/or positive lymph nodes Stage IV - Distant metastases; pleural effusion must have a positive cytology to be classified as stage IV; parenchymal liver metastases equals stage IV

except those patients with stage 1 and low risk characteristics The standard treatment for ovarian cancer start with staging and cytoreductive surgery For post operative treatment , chemotherapy is indicated in all patients with ovarian cancer except those patients with stage 1 and low risk characteristics Treatment

The 5-year survival rates are as follows: Prognosis The 5-year survival rates are as follows: Stage I - 73% Stage II - 45% Stage III - 21% Stage IV - Less than 5%

Prevention 1 OCP 2 Screening 3 4 5 Tubal ligation and hystrectomy Women who use ocp for three years or more reduce their risk of ovarian cancer by 30%-50% 1 OCP 2 Screening 3 Bilateral salpingo Oophrectomy For each year that women take ocp ,her risk of ovarian cancer is reduced by about 5% on average 4 Pregnancy and Breast feeding 5 Tubal ligation and hystrectomy

Prevention 1 OCP 2 Screening 3 4 5 Tubal ligation and hystrectomy Average women who used ocp for more than one year ,the protective effect lasted 2-3 decades after cessation of use 1 OCP 2 Screening 3 Bilateral salpingo Oophrectomy One analysis estimated that after 5 years of ocp ,nulliparous womwn can reduce their risk to the level seen in parous women who never used ocp 4 Pregnancy and Breast feeding 5 Tubal ligation and hystrectomy

Prevention 1 OCP 2 Screening 3 4 5 Tubal ligation and hystrectomy Another study show that 10 years of ocp use by women with positive family history can reduce their risk to a level below that for women with no family history who never used ocp 1 OCP 2 Screening 3 Bilateral salpingo Oophrectomy 4 Pregnancy and Breast feeding 5 Tubal ligation and hystrectomy

1 OCP The periodic use of trasvaginal ultrasonography and CA125 tumor marker is recommended in high risk women 2 Screening 3 Bilateral salpino Oophrectomy 4 Pregnancy and breast feeding 5 Tubal ligation and hystrectomy

1 2 3 4 5 Pregnancy and breast feeding OCP Surgical prophylaxis decrease the risk by at Least 90% but dose not Completely eliminate the risk WHY? Because ovarian cancer can be develop in the thin lining of the abdominal cavity that cover the ovaries . women who have had their ovaries removed can still get a similar but less common form of cancer called primary Peritoneal cancer OCP 2 Screening 3 Bilateral salpigo Oophrectomy 4 Pregnancy and breast feeding 5 Tubal ligation and hystrectomy

1 2 3 4 5 Pregnancy and breast feeding OCP Who is prophylaxis Oophrectomy recommended For? Patients with inherited mutation in the BRCA gene ,older than 35 year who have completed their families are the best Candidates Patients with family history of breast or ovarian cancer but no known genetic mutation 2 Screening 3 Bilateral salpigo Oophrectomy 4 Pregnancy and breast feeding 5 Tubal ligation and hystrectomy

Having at least one child lower the 1 OCP Having at least one child lower the Risk of developing Ovarian cancer Breast feeding for a year or longer Also reduce the risk of ovarian cancer 2 Screening 3 Bilateral salpingo Oophrectomy 4 Pregnancy and Breast feeding 5 Tubal ligation And hystrectomy

The nurses health study which followed 1000 OCP The nurses health study which followed 1000 Women for 20 years found asubstatial reduction in ovarian cancer risk in women who had tubal ligation and hystrectomy but it was more with the tubal ligation 2 Screening 3 Bilateral salpingo Oophrectomy 4 Pregnancy and Breast feeding 5 Tubal ligation And hystrectomy

The suggested mechanism of protection: 1 OCP The suggested mechanism of protection: By prevention of possible upward migration of carcinogens through the vagina, the cervix and fallopian tube into the peritoneal cavity 2 Screening 3 Bilateral salpingo Oophrectomy 4 Pregnancy and Breast feeding 5 Tubal ligation And hystrectomy

Take a home message

Ovarian cancer is the most common lethal gynecological malignancy and it represent the fifth cancer death in women in general It has many risk factor ,the most important one is the hereditary predisposition . No organization currently recommend the screening in asymptomatic women

Thank you