Malignant ovarian tumors

1. MALIGNANT Ovarian Tumor Dr Kanupriya Dr Rajeev

2. Epidemiology Risk factors Pathology and pathogenesis Diagnosis Screening Staging Prognosis Management

3. Ovarian malignancies represent the greatest challenge of all the malignancies because of its high mortality. Ovarian cancers -6% of all cancers among women Approximately 27% of gynecologic cancers are of ovarian origin About 53% of all the deaths of gynecological cancers are of ovarian origin (highest fatality to case ratio) American cancer society incidence

4. Incidence of ovarian cancers are highest in Sweden (19.6/100000) united states (15.4/100,000) and lowest in Japan (10.1/100,000) Incidence in India 0.9 to 8.4 per 100,000

5. The “silent killer”: asymptomatic in early stages 75% diagnosed with advanced stage disease; 5-year survival only 10-28% Woman’s lifetime risk of developing sporadic epithelial ovarian cancer is 1%-1.5% in developed nations and 0.75% in India. dying from ovarian cancer is 0.5%

6. Age Rare before 40yrs, increases steadily thereafter, peaks at 65-75yrs. Reproductive history early menarche, nulliparity or age >30 at first child-bearing, and late menopause Nulliparity is the most important non genetic factor. Fertility drugs prolonged use especially without achieving pregnancy Personal history of breast cancer Hormone replacement therapy > 10 years May be associated with 30% increased risk Talcum powder Some studies have shown slightly increased risk in women who use talc powder on genital area American Cancer Society 2001

7. Hereditary breast-ovarian cancer syndrome (HBOC) Hereditary site – specific ovarian cancer syndrome (HSSOC) Hereditary nonpolyposis colon cancer syndrome (HNPCC) * Inherited - 10% of ovarian cancers while 90% sporadic * Mode of inheritance is autosomal dominant *Occurs 10 years younger than sporadic

8. Lifetime risk of ovarian cancer is estimated - 39 % of BRCA 1 mutations 11% with BRCA2 mutations Life time probability of ovarian cancer 1.6 % without family history 5% if one relative is affected 7% if two relatives affected

9. ~7% of hereditary ovarian cancer cases Responsible genes: mutation in mismatch repair genes (MMR) including MLH1, MSH2, and MSH6 Predominance of early onset proximal colon cancer, ca ovary and endometrium . Estimated lifetime risk of ovarian cancer 10-12%.

10. Multiparity : First pregnancy before age 30 • Oral contraceptives: d ecreases approx 11% per year of use. Max of 46% after 5 years of use . • Tubal ligation • Hysterectomy ( Salpingectomy / Fimbriectomy ) • Bilateral oopherectomy -↓ risk by 80% to 95% • Lactation

11. Role of ovulation in the pathogenesis of the malignancy. Risk is related directly to the number of uninterrupted ovulatory cycles. As repair follows multiple ovulations, the surface epithelium of the ovary often extends into the ovarian stroma to form inclusion glands and cysts.

12. Incessant ovulation Retrograde menstruation hypothesis. Retrograde transportation of carcinogens from lower genital tract. Exposure of ovarian epithelium to persistently high levels of pituitary gonadotropins . Te Linde's

13. Very recently, Lee et al. have proposed many high-grade serous carcinomas actually arise in the mucosa of the fimbriated end of the fallopian tube.

14. THEORY TO IMPLICATE FT Ovary has no cells of Mullerian origin. FT has cells of mullerian origin i.e. tall mucuos secreting ciliated columnar cells. SOC are cells of mullerian origin i.e. columnar epithelium. HGSOC express mullerian marker PAX8.

15. The epithelium, via neoplastic transformation, may exhibit differentiation toward a variety of müllerian -type cells Serous   fallopian tubal lining Mucinous Intestinal  gastrointestinal mucosa Müllerian  endocervix Endometrioid  endometrial glands Brenner/transitional  bladder Clear cell  mesonephric (renal cell)

16. PRIMARY(80%) 1)Surface epithelial – 80-90 % 2)Non-epithelial Germ cell tumors – 15-20% Sex cord stromal – 5-8% SECONDARY(20%) 1) Typical 2) Atypical ( Krukenberg ) Dutta Gynae

17. Serous ( tubal) ----75-80% Mucinous ( endocx & intestinal )-----8-10% Endometrioid -----10% Transitional cell – Brenner-------<1% Clear cell-----<1% Novak's Gynecology

18. All types can be benign, borderline , or malignant, depending upon; Benign Gross : mostly cystic Microscopic ; fine papillae, single layer covering (no stratification), no nuclear atypia , no stromal invasion) Borderline Gross ; cystic / solid foci Microscopic ; papillary complexity, stratification, nuclear atypia , no stromal invasion Malignant Gross ; mostly solid & hemorrhage / necrosis Microscopic ; papillary complexity, stratification, nuclear atypia , stromal invasion

19. Formed by cells that resemble internal lining of fallopian tube. Most common. 75% of epithelial ovarian tumor. Most common in 4 th & 5 th decades of life Bilateral in 50% of cases.

20. Malignant (low grade serous and high grade serous carcinomas) Stromal invasion . Abundant delicate to coarse papillae Psammoma bodies in 80% per-se do not denote malignancy . Novak's PSAMMOMA BODIES

21. These are extracellular round laminar dark eosinophilic collections of calcium.

22. Low grade: papillary and glandular structures predominate High grade: solid sheets of cells , high mitotic activity , nuclear pleomophism

23. 8-10% of epithelial ovarian tumors. Largest ovarian tumors; may fill entire abdominal cavity. 5% are malignant. Bilateral in 8-10% cases. Cystic tumor; have loculi lined with mucin secreting epithelium. Cut surface shows honey-comb appearance. If it ruptures, may lead to formation of pseudomyxoma peritonei & adhesion formation

24. Resemble either those of the endocervical epithelium ( endocervical or mullerian type) or, more frequently, those of the intestinal epithelium ( intestinal type) Histologically , distinction may be impossible without clinical correlation. Irregular glandular spaces lined with a layer of tall columnar cells

25. 6-8% of epithelial tumors. Most are unilateral (40% are bilateral ) Almost all are malignant Associated with endometrial cancer (15-20%) Patient may have concurrent endometriosis (10-20%) May be cystic or solid Content tends to be hemorrhagic rather than serous or mucinous Resembling proliferative endometrial glands

26. Clear, peglike or hobnail-like cells. Most clear cell ovarian tumors are malignant. 50–70% have endometriosis One-fourth of all clear cell tumors arise in the lining of benign endometrioid cyst. These tumours are almost invariably high grade (grade 3) , hence not graded.

27. Resemble those of the internal lining of the urinary bladder . Borderline brenner tumors – surgical removal results in complete cure . Malignant Brenner – benign or borderline when coexisting with invasive transitional cell carcinoma Transitional cell carcinoma- when primary resembles transitional cell ca of Bladder without a recognisable brenner tumor -- sensitive to chemotherapy , more favourable prognosis .

28. Germ Cell Tumors Seminoma , Dysgerminoma ( primitive germ cells) Embryonic, ectoderm, mesoderm, endoderm Teratoma ( hcg - AFP-) Extra embryonic structures ( Vitelline ) Endodermal Sinus tumour (AFP+ HCG-) (Yolk Sac Tumour ) ( Trophoblastic ) Choriocarcinoma (AFP- HCG+) Totipotent cells Embryonal Carcinoma AFP (+) hCG (+) Embryonic differentation AFP (-) hCG (-) mature immature NOVAKS

29. Germ cell tumors -20-25% of all ovarian cancers Benign 97% ,malignant 3% M.C age – young women. In 1 st two decades of life, 70% are of Germ cell origin. Rapidly growing; Palpable abdominal mass and pelvic pain. FIGO staging same as epithelial ovarian tumor

30. Commonest malignant germ cell tumors (30 to 40% ) 75 % occur between 10 to 30 years of age. Rare after 50yrs. Consists of germ cells that have not differentiated to form embryonic or extraembryonic structures . Tumor marker - Elevated LDH , HCG or AFP As they present relatively at early stage - surgery followed by radiation has excellent cure rate . Loss of fertility is a problem. 85% of all patients with dysgerminoma are younger than 30 yrs , CONSERVATIVE THERAPY & PRESERVATION OF FERTILITY of major consideration .

31. 3 rd most frequent malignant GCT of ovary. Median age 16 – 18 yrs Unilateral in 100 % hence biopsy from opposite ovary is not needed Highly malignant with rapid growth Abdomen or pelvic pain (75 %) , Asymptomatic pelvic mass (10%) Gross appearance soft grayish brown with cystic areas Histology – SCHILLER DUVAL bodies Tumor maker- AFP correlates extent of disease & monitoring response to treatment Schillar Duval body with its central capillary and mantle of endoderm

32. MATURE CYSTIC TERATOMA Tissues usually derived from 2 or 3 germ cell layers. Accounting 95% of all ovarian teratomas Age < 20 years Clinical manifestation related to size ; TORSION most common complication – 16% Ovarian cystectomy appears to be adequate .

33. Has age specific incidence – Mc in first 2 decade According to Norris et al the quantity of immature neural tissue alone determines the grade . Grade I – mature teratoma containing only rare immature foci Grade III- large portion embryonal tissue with atypia and mitotic activity Rarely bilateral. So present method of therapy unilateral SALPINGOOPHERECTOMY with wide sampling of peritoneal implants .

34. Most malignant but rare (4%). Very young (4-28yrs) Median age is 14yrs. Manifests as abdominal mass pelvic mass. Associated with hormonal abnormalities (may secrete estrogen). Tumor makers - AFP, HCG

35. Extremely rare Composed of numerous embryoid bodies that resemble morphological normal embryo. Occur in very young, premenarcheal girls. Highly malignant .least sensitive to chemo & radiotherapy

36. Atleast 2 or more malignant germ cell elements, one of which is primitive. Components – dysgerminoma (commonest) yolk sac tumor, immature teratoma, embryonal ca , choriocarcinoma, and polyembryoma . Most significant component of the MIXED GC tumor determines therapy and follow-up .

37. Classification the sex cord- stromal tumors are divided into : Granulosa cell tumor Thecoma – fibroma group Sertoli-Ledyig cell tumors( Androblastoma ) Gynandroblastoma Sex cord tumor with annular tubules Unclassified Steroid cell tumors

38. 10% of all solid tumor, Bilateral in 2% Two SUBTYPES : Adult and Juvenile Adult GC – (95%) MC in postmenopausal . Avg age is 50years.Associated with ESTROGEN production. Endometrial HYPERPLASIA ( 25-50%) and Ca endometrium (5-10%) . Juvenile GC – In children and young adults ; 90% before puberty. Mean age at diagnosis is 13 years. Menstrual irregularities , amenorrhea, precocious puberty. True GC tumors are low grade; confined to one ovary with EXCELLENT PROGNOSIS : long term survival 75-90 %

39. M/E- classic adult granulosa cell is round/ovoid with scant cytoplasm. “ COFFEE BEAN ” grooved nuclei are characteristic CALL- EXNER BODIES- adult granulosa cells show a tendency to arrange themselves in small clusters or rosettes around a central cavity, resembling primordial follicles.

40. THECOMA-FIBROMA GROUP THECOMA FIBROMA Rarely malignant. In postmenopausal women; typically in 60’s. Most hormonally active. Usually produce excess estrogen. Abnormal bleeding , pelvic mass. Cells resemble theca cells B/L involvment rare. Surgical resection is curative. Generally benign. Perimenopusal and menopausal women. Hormonally inactive. 1% women present with MEIG’S SYNDROME( TRIAD of solid ovarian mass, ascites and pleural effusion). Arise from spindled stromal cells that form collagen. Malignant transformation in 1% cases. WILLIAMS GYNAE

41. Sertoli-Leydig cell tumour ( Arrhenoblastoma ) Extremely rare(0.2% of ovarian cancers) Occur most frequently in 3 rd or 4 th decade 75% seen in women <40 yrs Produce androgens  clinical virilisation in 70-85% Signs of virilisation  oligomenorhoea f/b amenorrhoea , breast atrophy, acne, hirsuitism , clitoromegaly , deepening of voice, receding hair line Rarely estrogenisation ( iso -sexual precocity, irregular or postmenopausal bleeding) seen. NOVAK'S GYNAE

42. Metastatic tumours About 5-6% of ovarian tumours are metastatic most frequently from the female genital tract,breast & GIT (pylorus, colon, rarely small bowel, pancreas, gall bladder) Two forms of secondary ovarian carcinoma Growth corresponds in its histology with its primary growth Dissemination by implantation from metastasis within peritoneal cavity Retrograde lymphatic spread Ovarian tumours are much larger than other secondary deposits Solid, irregular surface, nearly always bilateral, ascitis is common, peritoneal metastasis ( omentum )

43. Krukenberg tumour Usually bilateral Most often arise from primary carcinoma of stomach(70%), large bowel (15%), breast (6%) Smooth surface, slightly bossed, freely movable in pelvis No infiltration through the capsule, no tendency to form adhesions Tumour retains the shape of normal ovary, solid waxy consistency Histologically , cellular or myxomatous stroma , scattered signet ring cells (ovoid cell with granular cytoplasm, nucleus compressed against one pole of the cell)

44. ̴̴75% to 85% of patients with epithelial ovarian cancer are diagnosed at the time when their disease has spread throughout the peritoneal cavity. Our main aim is to identify women at high risk ,offer management option .. Suspect and establish diagnosis and treat cancer aggressively

45. Symptoms are Non specific amd vague. -Bloating ,abdominal distension -Pelvic or abdominal pain -Difficulty eating or feeling full quickly -Urinary symptoms ( frequency and urgency) Symptoms present for less than one year and occur on more than 12 days per month .

46. Signs Anaemia Left Supraclavicular (Virchow’s) & inguinal lymphadenopathy Unilateral non-pitting oedema of legs Tumours are often bilateral & fixed Ascitis , abdominal lump, enlarged liver Vaginal examination: fixed nodules in POD, adnexal massess felt separate from uterus Pleural effusion

47. TRANSVAGINAL SONOGRAM SERIAL CA125 Testing

48. Initial imaging modality of choice for benign vs malignant Results of screening trials have consistently demonstrated that US detects more stage I ovarian carcinomas than CA125 levels and physical examination TVS showed very high sensitivity (>95%) for detection of early stage carcinoma. Each ovary is measured in three dimensions. Ovarian volume is calculated using the prolate ellipsoid formula (L x H x W x 0.523). Premenopausal women vol >20cm 3 postmenopausal women vol >10cm3 Any solid or papillary projection from tumor wall ABNORMAL

49. Most valuable clinical tool by combining serum CA125 values with ultrasound findings and menopausal status to calculate a Risk of Malignancy Index (RMI). RMI = U x M x CA125 U is ultrasound score. 1 point each for : multilocular cysts, solid areas, metastasis, ascites and bilateral lesions. M is menopausal status ; scored as 1 = pre-menopausal and 3 = post-menopausal Serum CA125 in IU/ml and can vary between 0 and hundreds or even thousands of units.

50. It yielded a sensitivity of 85% and a specificity of 97%. LOW RISK: RMI <25 MODERATE RISK: RMI 25-250 HIGH RISK: RMI >250 Risk of cancer is 75% when RMI value is >250 DUTTA GYNAE

51. Serum CA125 has been widely used as marker for possible epithelial ovarian ca in assessment of pelvic mass. Poor sensitivity (elevated in only 25-50% of women with Stage I disease) Poor specificity (elevated in many gynecologic and non-gynecologic malignancies and benign conditions). False positive results common. Postmenopausal women = > 35 U/ml Premenopausal women = > 200 U/ml CA125 is important tumor marker for diagnosis , treatment and follow up care of patients with epithelial ovarian ca , can be used to determine response to t/t , relapse and survival.

52. Benign conditions Endometriosis Uterine fibroids PID Pregnancy Menstruation Diverticulitis Pancreatitis,liver disease Renal failure Appendicitis, IBD Malignant conditions Cervical CA Fallopian tube CA Endometrial CA Pancreatic CA Colon CA Breast CA Lymphoma Mesothelioma

53. Several other markers studied Human epididymis protein 4 Mesothelin B7-H4 Decoy receptor 3 Spondin 2 OVA1 is an FDA-cleared blood test that uses results of 5 biomarkers ( transthyretin , apolipoprotien A1, transferrin , beta-2 microglobin and CA-125), with an algorithm to indicate the probability of malignancy of an ovarian mass. Sensitivity : 93%, specificity: 43% OvaSure screening test- 6 biomarkers Leptin , prolactin , osteopontin , IGFII, MIF and CA-125. Not recommended. WILLIAMS GYNAE

54. Several publications have demonstrated HE4 ‘s superiority over CA125 . Specifically , HE4 ‘s ability to distinguish benign diseases with malignancies( ie its sensitivity ) As a single marker, HE4 had the highest sensitivity at 72.9% (specificity 95%) Combined, CA125™ and HE4 yielded the highest sensitivity at 76.4% (specificity 95%) The combination of CA125 and HE4 added 33.1% to the sensitivity of CA125 alone and 4.5% to the sensitivity of HE4 alone.

55. Recently, a more sensitive risk of ovarian cancer a lgorithm (ROCA) has been developed. This algorithm is based on the slope of serial CA125 measurements drawn at regular intervals. It has been proposed to increase the performance of single-threshold measurements of CA-125 concentrations. ROCA method is being evaluated in conjunction with TVS as a two-stage screening process, and results from trials are pending.

56. Patterns Of Spread 1. Transcoelomic Most common & earliest mode by exfoliation of cells which implant along surfaces of peritoneal cavity Follows circulatory path of peritoneal fluid Metastasis typically seen on POD, paracolic gutters, right hemidiaphragm , liver capsule, peritoneal surface of intestine & mesenteries, omentum It seldom invades intestinal lumen, but progressively agglutinates loops of bowel  functional intestinal obstruction  carcinomatous ileus

57. 2.Lymphatic First involves pelvic lymph nodes through broad ligament Advanced stage disease  retrograde dissemination via lymphatics to round ligament to inguinal lymph nodes follows ovarian vein to precaval & paraaortic lymph nodes 3.Hematogenous Hematogenous dissemination at the time of diagnosis is uncommon Spread to vital organs parenchyma (lungs & liver) occur only in 2-3% patients

58. FIGO staging of Ca Ovary

59. MANAGEMENT OF OVARIAN TUMORS

60. Prognostic factors affecting the Outcomes Pathological factors: Histologic type: Clear cell & Mucinous histologies – poorer survival low malignant potential – better survival b) Grade of tumor: poorly differentiated – poorer survival c)Stage of disease: According to FIGO BIOLOGICAL FACTORS: Aneuploidy poorer prognosis compared to diploidy CLINICAL FACTORS: Extent of residual disease post primary surgery , Volume of disease: small volume disease have better prognosis despite the stage Age: Older age poorer prognosis

61. Management: Preoperative evaluation Surgical management Chemotherapy NACT Follow up Management of commonly encountered tumors 67

62. PREOPERATIVE EVALUATION CBC, Coagulogram , LFT, RFT ECG/ CXR Urine R/E & C/S F/PP Sugars IMAGING: TAS/ TVS CECT abdomen & pelvis / MRI/ PET Scan Paracentesis Rule out other primary sites : Mammography GI Endoscopies Tumor markers 68

63. ROLE OF FNAC Diagnostic cytology has poor sensitivity to detect malignancy Aspiration of a malignant mass may induce spillage and seeding of cancer cells into the peritoneal cavity, thereby changing the stage and prognosis. INDICATION : Advanced ovarian cancer patients who are medically unfit to undergo surgery permitting initiation of neoadjuvant chemotherapy(NACT) 69

64. MANAGEMENT SPECTRUM PRIMARY SURGERY 1. EARLY STAGE OVARIAN CA( stage 1 and stage 2) COMPREHENSIVE SURGICAL STAGING FERTILITY SPARING SURGERY 2. ADVANCED STAGE OVARIAN CA PRIMARY CYTOREDUCTIVE SURGERY NEOADJUVANT CHEMOTHERAPY AND INTERVAL CYTOREDUCTIVE SURGERY LAPAROSCOPY SURGERY SECONDARY SURGERY SECOND LOOK LAPAROTOMY

65. COMPREHENSIVE SURGICAL STAGING Vertical midline abdominal incision Peritoneal cytology. Minimum of 25cc should be sent. In the absence of ascites , separate saline washings should be obtained from (a ) pelvic cul-de-sac, (b) right paracolic space, (c) left paracolic space, and (d) undersurface of each hemidiaphragm . The ovarian tumor should be inspected for presence of papillary excrescences or rupture of the capsule. Abdominal inspection and palpation in a systematic fashion. 71 TE LIINDE’S

66. What is the sequence of systemic exploration of abdominal organs???

67. Beginning with– peritoneum of cul-de-sac and small bowel mesentry . Ascending colon Liver Omentum Undersurface of right and left hemidiaphragm Stomach And Finally---- Tranverse colon, spleen, descending colon and bladder peritoneum.

68. TAH + BSO Infracolic omentectomy in patients with epithelial ovarian cancer and an omental wedge biopsy taken in patients with germ-cell or stromal tumors . Suspicious areas to be biopsied Retroperitoneal lymph node sampling Appendectomy should be performed in all patients with mucinous epithelial cancers involving the ovary. Operative findings present at staging laparotomy must be carefully documented. 74 TE LINDE’S

69. SURGICAL THERAPY BORDERLINE TUMOUR Primary resection- Unilateral oophorectomy no subsequent chemo or RT required. Stage I epithelial ovarian cancer : TAH + BSO with omentectomy and lymph node sampling ovarian cancer 75

70. STAGE II TAH + BSO with careful surgical staging Followed by chemotherapy usually platinum based . 76 ovarian cancer

71. Indications for fertility sparing surgery ?

72. Fertility sparing surgery: Desirous of preserving fertility Pt & family agrees for close follow up No e/o dysgenetic gonads Unilateral GCT, Sex cord stromal tumor, borderline tumor. Early stage ovarian carcinoma (IA) Follow up : Routine periodic pelvic examinations and determinations of serum CA125 levels. Endometrial biopsy / curettage as 5% to 15% of patients with granulosa cell tumor develop endometrial cancer or hyperplasia. Generally, the other ovary and the uterus are removed at the completion of childbearing.

73. ADJUVANT THERAPY ??----- RISK ASSESSMENT Benefit of post-op or adjuvant therapy depends on risk of relapse. EARLY STAGE OVARIAN CANCER classified into LOW RISK HIGH RISK Stage IA or IB, grade 1 and 2 Stage IA or IB, grade 3 Stage IC Standard treatment is SURGERY ALL Stage 2 ALONE. 5year survival is atleast 95%. [ No role of adjuvant therapy] Platinum based chemotherapy. Optimal regimen & duration of therapy ELUSIVE

74. ADVANCED OVARIAN CA Stage III/ STAGE IV MAXIMUM CYTOREDUCTIVE SURGERY F/B COMBINATION CHEMOTHERAPY

75. Stage III/ IV: PRIMARY CYTOREDUCTIVE SURGERY : Goal is to reduce the amount of tumor as much as possible in a patient with metastatic ovarian cancer. It is considered in context of responsiveness of residual tumor to post-operative therapies. Lesser the residual tumor volume, better is the survival. OPTIMAL DEBULKING- Minimal residual disease ≤ 1-2 cm in greatest dia. SUBOPTIMAL DEBULKING- Bulky residual disease > 1-2 cm in dia. Complications: Infection, hemorrhage prolonged ileus cardiopulmonary problems 81 TE LINDE'S

76. PRINCIPLES: Close observation & treatment of any complications during chemotherapy Assessment for response & monitoring for any long term complications. Chemosensitivity / resistance assay.

77. Number of cycles of treatment??

78. NUMBER OF CYCLES OF TREATMENT 6-8 cycles: advanced-stage disease 3 to 6 cycles: earlier-stage disease

79. CHEMOTHERAPY Platinum-based combination chemotherapy is generally recommended. They can be used singly or in combination with Paclitaxel . Currently, Paclitaxel and Carboplatin combination found to have better survival rate. 85

80. Regime followed----- Before starting chemotherapy, Hydrate the patient. Inj. Palonosetron , Inj avil , inj dexameethasone , inj rantac given ½ hr before starting chemotherapy. Inj PACLITAXEL 175mg/m 2 IV infusion in D5% glass bottle through CODON SET. Inj. CARBOPLATIN 450mg(5-6 AUC) IV infusion Every 3 weekly with Monitoring of CHG, RFT,LFT & Serum electrolytes. DAY 1

81. INTRAPERITONEAL CHEMOTHERAPY Patients with low volume residual disease after surgical cytoreduction are potential candidates for intraperitoneal (IP) therapy. Not been accepted universally as a result of issues with catheter placement and therapy associated toxicities 87

82. FOLLOW UP Complete clinical remission is defined as no objective evidence of disease Recommendations : After the completion of primary surgery and chemotherapy ; Visits : every 2-4 mo for 2 y, then twice yearly for 3 y, then annually after 5 y CA-125/ other tumor markers every visit if initially elevated CBC / LFT/RFT as indicated Complete physical & Pelvic examination Chest/ abdominal/ pelvic USG/ CT/ MRI PET-CT, or PET as clinically indicated 88

83. ROLE OF NACT INDICATIONS: Poor surgical candidates Possibility of suboptimal resection Stage IIIC/IV Giving 3-6 cycles of CT upfront will reduce tumor burden, makes subsequent surgery more feasible ( Allow maximal cytoreduction of residual tumor) surgery post NACT c/as : INTERVAL DEBULKING SURGERY Prior to giving NACT, the pathologic diagnosis should be confirmed by either fine needle aspiration, CT-guided biopsy or paracentesis . 89

84. SECOND LOOK SURGERY performed on a patient with no clinical evidence of persistent tumor for the purpose of determining disease status after a planned interval of treatment with chemotherapy Primary purpose not debulking 0r treating complication Classification of findings Negative - 30% to 50%( seen with Early-stage disease ) Microscopically positive -20% Macroscopically positive- 30% to 50% NOT RECOMMENDED due to increased surgical morbidity 90

85. ROLE OF LAPAROSCOPY Primary surgery for early-stage ovarian cancer Restaging of unstaged ovarian cancer Assessment of resectability Intraperitoneal catheter placement Second-look surgery Secondary cytoreductive surgery. Port site metastasis 1% to 2% 91 ovarian cancer

86. DYSGERMINOMA TREATMENT: SURGERY: TAH &BSO, if fertility not required. Unilateral oophorectomy - minimum surgery CHEMOTHERAPY Advantage : fertility preservation RADIOTHERAPY Very Radiosensitive problem :Loss of fertility

87. GRANULOSA CELL TUMOR Unilateral salpingo-oophorectomy Ovarian biopsy if enlarged Endometrial biopsy if uterus left Palliative RT for pelvic recurrences (otherwise not useful). EMBRYONAL CARCINOMA Rx-: Unilateral oophorectomy followed by CT with BEP