Tis/0 T1abc T2abc T3abc M1=IVTNM staging N0 0 Iabc IIabc IIIabc N1=IIIC IIIC M1=IV IV¨ T1: Limited ¤ to one(a) or both(b) ovaries ¤ + ruptured capsule, tumor on ovarian surface, +ve cells in peritoneum (C)¨ T2: Pelvic extension ¤ Tubes or uterus (a), ¤ other pelvic organs (b) ¤ +ve cells in peritoneum (C)¨ T3: Extra-pelvic extension ¤ microscopic (a), ¤ macroscopic <2cm(b), ¤ macroscopic >2cm(c)¨ No T4:¨ N1: +ve LNs¨ M1 Distant mets¨ Grade: 1,2,3
Notes¨ Liver capsule metastasis is T3/Stage III; liver parenchymal metastasis, M1/Stage IV.¨ Pleural effusion must have positive cytology for M1/Stage IV.¨ Primary peritoneal adenocarcinoma and Fallopian tube carcinomas are staged using the ovarian staging system
Prognosis¨ Stage: ¤ T ¤ N ¤ M¨ Grade¨ Response to initial therapy ¤ No benefit from two consecutive regimens is very poor¨ Recurrence¨ Time to recurrence: ¤ Recurrence less than 6 m of end of chemo (P resistant) is very poor ¤ Give non-paltinum non-taxane drug¨ Others: old age, comorbidities, poor PS
Screening¨ No proven value¨ Whether one or more of the following is used: ¤ CA12-5 ¤ US: conventional or transvaginal ¤ CT ¤ human epididymis protein 4 (HE4)
Risk factors¨ Younger age at pregnancy and first birth (25 y)¨ Oral contraceptives ,¨ breast-feeding.¨ Family history ¤ BRCA1 and BRCA2 ¤ HNPCC
Workup¨ History including family history¨ Abdominal/pelvic exam¨ Imaging: ¤ Ultrasound and/or abdominal/pelvic CT ¤ Chest imaging¨ Lab: ¤ CA-125 or other tumor markers as clinically indicated ¤ CBC ¤ Chemistry profile with LFT’s ¤ Institutional pathology review¨ GI evaluation if clinically indicated
Treatment¨ Multidisciplinary team: ¤ Gynecological oncological Surgeon ¤ Medical Oncologist¨ Modalities ¤ Surgery: extensive vs limited ¤ Chemotherapy: IV vs IP ¤ RT: limited role if any n Whole abd RT consolidation in low-bulk stage III n Palliative RT: for local and distant symptomatic disease¨ Stages: ¤ I ¤ II-III-IV
Surgery¨ Staging laparotomy with Maximum cytoreduction:¨ By gynecologic oncologist¨ Indications: operable stages I through IV ¤ aspiration of ascites or peritoneal lavage ¤ All peritoneal surfaces should be visualized, ¤ any peritoneal surface or adhesion suspicious should be excised or biopsied ¤ TH/BSO n USO with uterine preservation but with full staging laparotomy n Preserve fertility in young women n Indications: n stage I tumors and/or n low-risk tumors (early-stage invasive tumors, or LMP) ¤ Omentectomy ¤ Lymphadenectomy: ↑ DFS but not OS n Aortic n pelvic
Surgery for fertility preservation (FP)¨ FP not an option or MMT (carcinosarcoma), or stage II-IV EOC or stromal tumor: classic surgery¨ FP is an option à frozen section àif (Indications) ¤ stage I tumors and/or ¤ low-risk tumors (early-stage invasive carcinoma or stromal tumor & LMP) ¤ Germ cell tumors à limited surgery
Role of neoadjuvant chemotherapy¨ How? Cisplatin based chemo CB ¤ CBx 3 àsurgeryàCBx3¨ Role: ¤ Standardin inoperable bulky stage II to IV ¤ Controversial in operable disease: n same DFS and OS n (Vergote et al , 2008)
Non-optimal initial surgery¨ Occurs in: 1.Uterus intact 2. Adnexa intact 3. Omentum not removed 4. Documentation of staging incomplete 5. Residual disease, potentially resectable¨ What to do:¨ Depends on stage, grade, planned further therapy and is there a resectable residual ¤ With resectable residual: complettion of surgical staging ¤ With irresectable residual: chemox3-6àcompetion surgeryàcomplete the 6-8 courses
Role of neoadjuvant chemotherapy¨ How? Cisplatin based (CB) chemo IV ¤ CBx 3 àsurgeryàCBx3¨ Role: ¤ Standardin inoperable bulky stage II to IV ¤ Controversial in operable disease: n same DFS and OS n (Vergote et al , 2008)
Chemotherapy in ovarain CA¨ Systemic (IV) q 3w: ¤ Docetaxel plus carboplatin (DC): n D: 60-75 mg/m2 & C: AUC of 5-6 ¤ Paclitaxel plus carboplatin (TC) n C: AUC of 5-7.5 & T: 75 mg/m2 3-hour IV infusion ¤ Paclitaxel plus Cisplatin (TP) n T 135 mg/m2 IV 24-h IV infusion & Cisplatin (P) 75 mg/m2¨ Combined (intraperitoneal IP+IV) q 3w: ¤ D1: T 135 mg/m2 IV 24-h IV infusion ¤ D2: P 100 mg/m2 IP ¤ D8: T 60 mg/m2 (max BSA 2.0 m2)
IV vs IPArmstrong et al, N Engl J Med 2006;354:34-43¨ Stage III & residual <= 1cm¨ 6 cycles¨ Longest MOS: 67 m vs 50 m
IV vs IPArmstrong et al, N Engl J Med 2006;354:34-43
IV vs IPArmstrong et al, N Engl J Med 2006;354:34-43
IV vs IP¨ IV is the standard¨ Till more data accumulate, IP is an option for stage III with residual <=1cm, if tolerable¨ Needs catheter and experience¨ Expected poor tolerance to IP: ¤ Poor PS ¤ Comorbidities ¤ Old age ¤ Stage IV disease¨ If you start IP and intolerant, continue with IV
High-dose chemo and autoBMTMöbus et al, J Clin Oncol 2007;25(27):4187-4193¨ RCT¨ Cyclo-pacli x 6¨ Cyclo-paclix2 à HD carbo-paclix3 with stem cell support
Maintenance therapyMarkman et al J Clin Oncol 2003;21:2460-2465¨ In complete clinical remission: ¤ Negative clinical exam ¤ Negative CA125 ¤ Negative CT with LN <1cm¨ After 6-8 cycles of taxane- carbo¨ Pacli 175 q4w ¤ X 3 vs x 12¨ PFS: 21 vs 28 m¨ Stopped early for superiority
Follow-up Recommendations¨ by: ¤ H&P ¤ CA125 ¤ Other lab and imaging when necessary¨ Fequency: ¤ Q2-4m x 2y ¤ 63-6m x 3y ¤ Q12m thereafter
Clinical questions¨ WAHAT TO DO WITH ¤ Non-optimal initial surgery ¤ No or Partial response to initial chemo ¤ Complete response then: n Recurrence within 6 m n Recurrence 6-12 m n Recurrence > 12 m ¤ Biochemical failure: rising CA125 with no clinical or radiological evidence or progression.
Biochemical failure: rising CA125 with no clinical or radiological(CT/MRI +/- PET) evidence or progression.¨ Clinically relapse within 2-6 m¨ Options: ¤ Priorchemo: treat as new ¤ No-prior chemo:
ACCEPTABLE RECURRENCE THERAPIES Preferred Agents Other Agents¨ Cytotoxic Therapy ¨ Cytotoxic Therapy ¤ Combination if platinum sensitive ¤ Altretamine n Carboplatin/paclitaxel (category 1) ¤ Capecitabine n Carboplatin/docetaxel ¤ Cyclophosphamide, Ifosfamide n Carboplatin/gemcitabine ¤ Irinotecan n Cisplatin/gemcitabine ¤ Melphalan n Carboplatin/weekly paclitaxel ¤ Oxaliplatin n Carboplatin/liposomal doxorubicin ¤ Paclitaxel ¤ Single-agent if platinum sensitive ¤ Vinorelbine Carboplatin, Cisplatin, oxaliplatin n ¨ Hormonal Therapy: ¤ Single-agent non-platinum based if ¤ Anastrozole , Letrozole platinum resistant ¤ Tamoxifen n Docetaxel, Paclitaxel, weekly n Etoposide, oral Gemcitabine ¤ Megestrol acetate n Liposomal doxorubicin ¤ Leuprolide n Pemetrexed Topotecan ¨ Palliative localized radiation therapy¨ Targeted Therapy: Bevacizumab
Notes¨ primarily progress on two consecutive regimens without evidence of clinical benefits have diminished likelihood of benefiting from additional therapy. Decisions to offer supportive care, additional therapy, or clinical trials should be made on a highly individual basis.¨ Platinum-based combination therapy should be considered for platinum-sensitive recurrences.¨ Combination therapy with bevacizumab may be considered.
Optimal chemotherapy of recurrent ovarian cancer:Metanalysis of 13 trialsFung-Kee-Fung et al Curr Oncol 2007;14(5):195-208.¨ In five of the thirteen trials in which 100% of patients were considered sensitive to platinum-containing chemotherapy, further platinum-based combination chemotherapy significantly improved response rates (two trials), progression-free survival (four trials), and overall survival (three trials) when compared with single-agent chemotherapy involving carboplatin or paclitaxel. Only two of these randomized trials compared the same chemotherapy regimens: carboplatin alone versus the combination of carboplatin and paclitaxel. Both trials were consistent in reporting improved survival outcomes with the combination of carboplatin and paclitaxel. In one trial, the combination of carboplatin and gemcitabine resulted in significantly higher response rates and improved progression-free survival when compared with carboplatin alone. Median survival with carboplatin alone ranged from 17 months to 24 months in four trials.
Optimal chemotherapy of recurrent ovarian cancer:Metanalysis of 13 trialsFung-Kee-Fung et al Curr Oncol 2007;14(5):195-208.¨ 5 trials in chemosensitive disease: significant ¤↑ RR in 2 trials ¤ ↑ PFS in 4 trials ¤ ↑ OS in 3 trials¨ If combination platinum-based chemotherapy is not indicated, then a single platinum agent should be considered.
Optimal chemotherapy of recurrent ovarian cancer:Metanalysis of 13 trialsFung-Kee-Fung et al Curr Oncol 2007;14(5):195-208.¨ Platinum-refractory or platinum-resistant disease: ¤ Monotherapy should be considered because no advantage appears to accrue to the use of non-platinum-containing combination chemotherapy. ¤ Single-agent paclitaxel, topotecan, or pegylated liposomal doxorubicin have demonstrated activity in this patient population and are reasonable treatment options. ¤ No evidence either supports or refutes the use of more than one line of chemotherapy. ¤ Many treatment options have shown modest response rates, but their benefits over best supportive care have not been studied in clinical trials
Borderline Epithelial Ovarian Cancer¨ primary epithelial ovarian lesion with cytological characteristics suggesting malignancy, but without frank invasion¨ clinically indolent course and good prognosis.¨ Five-year survivals exceed 80%.¨ peritoneal implants characterises OC
Borderline Epithelial Ovarian Cancer¨ Treatment: ¤ Surgery as OC ¤ With peitoneal implants: n Non-invasive: observation n Invasive: observation or chemotherapy
Less Common Ovarian Histopathologies¨ germ cell neoplasms,¨ carcinosarcoma (MMMT), and¨ ovarian stromal tumors.¨ Early stage¨ Fertility preservation¨ Tumor markers: CA125, inhibin, AFP, BHCG
Germ Cell Tumors¨ Young age <35 y¨ Surgery: extensive or conservative¨ Post surgery: ¤ Observation in stage I dysgerminoma or immature teratoma ¤ Chemo (3-4 PEB): n embryonal or endodermal sinus tumors; n stages II-IV dysgerminoma or immature teratoma
Ovarian Stromal Tumors (Sex cord-stromal tumors)¨ Surgery (conservative in stage I or else extensive)¨ Post surgery treatment:¨ Stage I low risk: observation¨ Stage I high risk: observation, RT, PB chemo (BEP-TC) n Tumor rupture, n stage 1C, n poorly differentiated tumor, n tumor size greater than 10-15 cm132¨ Stage II-IV: radio or PB chemo,
Carcinosarcoma (Malignant Mixed Müllerian Tumors)¨ Surgery¨ Post surgical therapy ¤ Stage I: n Ifosfamide-based regimens ¤ Stage II-IV or recurrence: ¤ As ovarian CA