Ovarian tumors STAGING MANAGEMENT TREATMENT OF OVARIAN CYSTS

Ovarian tumors STAGING & MANAGEMENT

TREATMENT OF OVARIAN CYSTS AND BENIGN TUMORS • Ovarian cysts < 6 cms usually regress by absorption or spontaneous rupture and the patient may be managed conservatively over 2 menstrual cycles with monthly rectovaginal examination. • If regression fails to occur, assessment is indicated • Diagnostic tests include laboratory blood studies and pelvic examination. Usually, ultrasound studies with and without blood flow measurements to the involved ovary are used for diagnosis and to help determine the best therapy. • Some tumors require surgery to diagnose accurately, ruling out malignancy, or to treat. If one ovary must be removed, normal conception and childbirth is possible as long as a normal ovary remains on the other side.

Medication • Female hormones or clomiphene may be prescribed. These help shrink or destroy some tumors. Oral contraceptives are often used as the first step in treatment.

LAPAROSCOPY • Ovarian cyst and benign tumors can also be resected by this technique

Staging The Federation Internationale de Gynecologie et d'Obstetrique (FIGO) and the American Joint Committee on Cancer (AJCC) have designated staging.

Stage I ovarian cancer • limited to the ovaries. – Stage IA: tumour limited to 1 ovary, the capsule is intact, no tumour on ovarian surface and no malignant cells in ascites or peritoneal washings. – Stage IB: tumour limited to both ovaries, capsules intact, no tumour on ovarian surface and no malignant cells in ascites or peritoneal washings. – Stage IC: tumour is limited to 1 or both ovaries with any of the following: capsule ruptured, tumour on ovarian surface, malignant cells in ascites or peritoneal washings.

Stage II ovarian cancer • tumors involving 1 or both ovaries with pelvic extension and/or implants. – Stage IIA: extension and/or implants on the uterus and/or fallopian tubes. No malignant cells in ascites or peritoneal washings. – Stage IIB: extension to and/or implants on other pelvic tissues. No malignant cells in ascites or peritoneal washings. – Stage IIC: Pelvic extension and/or implants (stage IIA or stage IIB) with malignant cells in ascites or peritoneal washings.

Stage III ovarian cancer • tumours involving 1 or both ovaries with microscopically • confirmed peritoneal implants outside the pelvis. Superficial liver metastasis equals stage III. – Stage IIIA: microscopic peritoneal metastasis beyond pelvis (no macroscopic tumour). – Stage IIIB: macroscopic peritoneal metastasis beyond pelvis less than 2 cm in greatest dimension. – Stage IIIC: peritoneal metastasis beyond pelvis greater than 2 cm in greatest dimension and/or regional lymph node metastasis.

Stage IV ovarian cancer tumours involving 1 or both ovaries with distant metastasis. Parenchymal liver metastasis equals stage IV.

Management

Treatment Options • The treatment of ovarian cancers based on the • • stage of the disease which is a reflection of the extent or spread of the cancer to other parts of the body. It also depends on histologic cell type, and the patient's age and overall condition. There are basically three forms of treatment of ovarian cancer: – – – surgery Chemotherapy radiation treatment,

GENERAL GUIDELINES: • Standard treatment is surgery (staging and optimal debulking) followed by adjuvant chemotherapy in most cases. Even if optimal surgery is not possible, removing as much tumor as possible will provide significant palliation of symptoms. • Borderline lesions may be treated with conservative surgery

GENERAL GUIDELINES: • Germ cell tumors are treated with surgery and multiagent chemotherapy in most cases • Advanced epithelial ovarian cancer is very sensitive to chemotherapy with responses in the range of 70 -80% to first-line chemotherapy. The majority, however, relapse and ultimately die of chemotherapy-resistant disease. Second-line chemotherapy to date is disappointing in all forms of epithelial ovarian cancer with virtually no chance of successful second-line treatment following failure of initial regime.

SURGERY

Treatment of Ovarian Epithelial Cancer

Stage I • Generally a total abdominal hysterectomy, removal of both ovaries and fallopian tubes, omentectomy, biopsy of lymph nodes and other tissues in the pelvis and abdomen, is done. Young women whose disease is confined to one ovary are often treated by a unilateral salpingo-oophorectomy without a hysterectomy and removal of the opposite ovary being performed • Depending on the pathologist's interpretation of the tissue removed, there may be no further treatment if the cancer is low grade, or if the tumor is high grade the patient may receive combination chemotherapy.

Stage II • Treatment is almost always hysterectomy and bilateral salpingo-oophorectomy as well as debulking of as much of the tumor as possible and sampling of lymph nodes and other tissues in the pelvis and abdomen that are suspected of harboring cancer. After the surgical procedure, treatment may be one of the following: 1) combination chemotherapy with or without radiation therapy or 2) combination chemotherapy.

Stage III • Treatment is the same as for Stage II ovarian cancer. Following the surgical procedure, the patient may either receive combination chemotherapy possibly followed by additional surgery to find and remove any remaining cancer.

Stage IV • CYTOREDUCTIVE SURGERY/DEBULKING: – surgery to remove as much of the tumor as possible. – Most researchers consider residual disease of <1 cm to be optimal debulking surgery. followed by combination chemotherapy

Trial of 146 patients with stage III and IV ovarian cancer treated with cisplatin at Rosewell park Cancer Institute: SIZE OF RESIDUAL DISEASE SURVIVAL 5 YEARS 8 YEARS <1 CM 56% 42% 1 -2 CMS 19% 10% >2 CMS 13% 8. 7%

CHEMOTHERAPY • Prolongs remission and survival • Also used for palliative treatment in advanced n recurrent disease • Administered in all cases beyond stage Ia • Earlier single agents were used, nowadays combination therapy is favoured

CHEMOTHERAPY • No chemotherapeutic agent kills all cancer cells in one treatment , Tf treatment needs to be repeated several times • All agents used should be active against that particular tumor • should have different modes of action to avoid drug resistance n should have differenr mechanisms of toxicity.

CHEMOTHERAPY • This allows each of them to be used as nearv to the full dose as possible. • Drugs are given at 3 weeks intervals • Intraperitoneal chemotherapy is also done

• The initial treatment of ovarian cancer is called first-line therapy. • If the cancer continues to grow with first-line therapy or returns after first-line therapy, additional treatment, called second-line therapy, may be administered. • If the tumor continues to grow after second-line therapy, the next therapy is called third-line therapy, and so on.

First-Line Chemotherapy • First-line chemotherapy for ovarian cancer typically consists of two drugs given together. The combination =paclitaxel + platinum drug—either carboplatin or cisplatin. • Select women may benefit from administration of chemotherapy directly into the abdomen—called intraperitoneal therapy—in addition to conventional intravenous administration.

Second-Line Chemotherapy • The choice of drugs for second-line therapy depends largely on which drugs were administered for first-line therapy and how long it has been since the first-line therapy was stopped. • chemotherapy drugs) for the treatment of ovarian cancer that has returned: GEMZAR (gemcitabine HCl for injection) plus another chemotherapy, carboplatin, is indicated , 6 months after their first-line therapy;

Second-Line Chemotherapy • Hycamtin (topotecan HCl for injection) is indicated as a single agent (one drug) for the treatment of ovarian cancer upon failure of first-line therapy; • and Doxil (doxorubicin HCl liposome injection) is approved for use to treat women whose cancer has returned following first-line therapy.

NICE guidelines for the use of chemotherapy – It is recommended that paclitaxel in combination with a platinum-based compound or platinum-based therapy alone (cisplatin or carboplatin) are offered as alternatives for first-line chemotherapy (usually following surgery) in the treatment of ovarian cancer. – When relapse occurs after an initial (or subsequent) course of first-line chemotherapy, additional courses of treatment should be considered, using different treatment options.

NICE guidelines for the use of chemotherapy (contd. . ) – The following definitions are used by NICE: • Platinum-sensitive ovarian cancer: disease that responds to first-line platinum-based therapy but relapses 12 months or more after completion of initial platinum-based chemotherapy. • Partially platinum-sensitive ovarian cancer: disease that responds to first-line platinum-based therapy but relapses between 6 and 12 months after completion of initial platinum-based chemotherapy. • Platinum-resistant ovarian cancer: disease that relapses within 6 months of completion of initial platinum-based chemotherapy. Platinum-refractory ovarian cancer: disease that does not respond to initial platinum-based chemotherapy.

NICE guidelines for the use of chemotherapy (contd…) – Paclitaxel in combination with a platinum-based compound (carboplatin or cisplatin) is recommended as an option for the second-line (or subsequent) treatment of women with platinumsensitive or partially platinum-sensitive advanced ovarian cancer, except in women who are allergic to platinum-based compounds. – Single-agent paclitaxel is recommended as an option for the second-line (or subsequent) treatment of women with platinumrefractory or platinum-resistant advanced ovarian cancer, and for women who are allergic to platinum-based compounds. – PLDH (pegylated liposomal doxorubicin hydrochloride) is recommended as an option for the second-line (or subsequent) treatment of women with partially platinum-sensitive, platinumresistant or platinum-refractory advanced ovarian cancer, and for women who are allergic to platinum-based compounds.

NICE guidelines for the use of chemotherapy (contd…. ) Topotecan is recommended as an option for second-line (or subsequent) treatment only for those women with platinum-refractory or platinum-resistant advanced ovarian cancer, or those who are allergic to platinum-based compounds, for whom PLDH and single-agent paclitaxel are considered inappropriate.

REGIMENS IN OVARIAN CANCER REGIMEN DOSE CP CISPLATIN PACLITAXEL 75 mg/sq. m 135 -175 mg/sq. m CT CARBOPLATIN PACITAXEL AUC=5 135 -175 mg/sq. m DC CISPLATIN CYCLOPHOSPHAMIDE 75 mg/sq. m 750 mg/sq. m CAP CYCLOPHOSPHAMIDE DOXORUBICIN CISPLATIN 600 mg/sq. m 50 mg/sq. m 75 mg/sq. m BEP BLEOMYCIN ETOPOSIDE CISPLATIN 10 mg/sq. m x 3 days 20 mg/sq. m x 5 days 100 mg/sq. m

REGIMEN FOR NON-EPITHELIAL TUMORS VAC VBC BEP Vincistrene

SIDE EFFECTS

While chemotherapy drugs kill cancer cells, they also damage some normal cells, causing side effects. These side effects will depend on the type of drugs given, the amount taken, and how long treatment lasts. Temporary side effects might include the following: • • • nausea and vomiting loss of appetite hair loss hand foot rashes kidney or nerve damage mouth sores

• an increased chance of infection (from a shortage of white blood cells) • bleeding or bruising after minor cuts (from a shortage of platelets) • tiredness (from low red blood cell counts)

RADIOTHERAPY: • Now, has a very small role since platinum based protocols and paclitaxel have improved the median survival. • -However it can be used as a palliative treatment for metastatic bone or brain lesions or of localized recurrence to alleviate the pain.

• Also used in recurrent germ cell tumors especially dysgerminomas which is very radiosensitive. • Radioactive isotopes of gold-Au 198 and phosphorus-P 32 have been used intraperitoneally along with external radiotherapy. • However there’s no improvement in survival rate. • High incidence of bowel complications have been noted.

Recurrent Ovarian Epithelial Cancer • Detection of Recurrent Disease • Second-Look Surgery

Second-Look Surgery • The use of second-look surgery can help diagnose and manage ovarian cancer. • evidence of enhanced survival after this procedure is lacking. • It is defined as re-exploration n patients with advanced stage III and stage IV ovarian cancer’ after a standard course of chemotherapy have no clinical, biochemical, ro radiologic evidence of disease

The findings of second-look surgery are: • microscopically positive (grossly negative, but microscopically positive) • macroscopically positive (grossly and pathologically positive)

Treatment of Recurrent Cancer • Patients who develop recurrent cancer despite surgery and primary chemotherapy, and will be given salvage chemotherapy, may be placed into one of three groups (A-C):

GROUP A • are patients resistant to primary therapy and have shown tumor growth during treatment. This persisting tumor is considered to be refractory i. e. have absolute platinumresistance. Secondary non-cross resistant chemotherapies or biological therapies should be considered.

GROUP B • are patients who respond well to initial chemotherapy, but develop recurrent cancer within months after the end of primary care. This group with relatively platinum resistant tumor has an intermediate prognosis.

GROUP C • are patients who showed a good response to primary chemotherapy, and did not develop recurrent cancer for more than 6 months after the end of primary treatment. This group with platinum-sensitive tumor shows the best responses to re-treatment with a platinum-containing regimen.

prognosis • Overall 5 -year survival in ovarian epithelial carcinoma is low because of the preponderance of late-stage disease at diagnosis. – Stage I and II: 80 -100% – Stage III: 15 -20% – Stage IV: 5% • Patients under 50 in all stages have considerably better 5 -year • • survival than older patients (40% compared to 15%) Dysgerminomas treated by surgery and radiation have an excellent cure rate in both early and late-stage disease Endodermal sinus tumour has poor prognosis.

prevention • Diet: a high-fat diet may play a role in the • • aetiology of ovarian cancer. Oral contraceptives appear to reduce the risk of ovarian cancer for up to 10 years following cessation of use. This protective effect appears to apply to patients with BRCA mutations as well. Patients who have used fertility drugs should be counselled as to their possible increase in risk of ovarian cancer.

TREATMENT OF BENIGN TUMORS • Diagnostic tests include laboratory blood studies and pelvic examination. Usually, ultrasound studies with and without blood flow measurements to the involved ovary are used for diagnosis and to help determine the best therapy. Laparoscopy is required in some cases, and rarely, a CT scan or MRI may be recommended. • Treatment may not be necessary, except to have regular pelvic examinations so the tumor's growth can be monitored. • Some tumors require surgery to diagnose accurately, ruling out malignancy, or to treat. If one ovary must be removed, normal conception and childbirth is possible as long as a normal ovary remains on the other side.

TREATMENT OF BENIGN TUMORS • Germ cell tumors are treated with surgery and multiagent chemotherapy in most cases • Advanced epithelial ovarian cancer is very sensitive to chemotherapy with responses in the range of 70 -80% to first-line chemotherapy. The majority, however, relapse and ultimately die of chemotherapy-resistant disease.

Treatment of Sensitive Cancer • Patients with recurrent chemotherapy-sensitive disease are usually treated again with primary chemotherapy usually carboplatin/paclitaxel, but toxicity must also be taken into consideration. • If carboplatin or cisplatin was used alone for primary therapy, taxol should be considered for salvage chemotherapy. • For low-volume disease, intraperitoneal chemo- or radiotherapy can be considered. These patients are also candidates for trials of high dose chemotherapy with autologous bone marrow support.