Ovarian Cancer Priya Gopalan 3/16/07
Epidemiology <ul><li>8th most common cancer type in women (estimated 22,430 new cases ) </li></ul><ul><li>5th most common ...
Risk factors <ul><li>Family history of ovarian/breast cancer  </li></ul><ul><li>Personal history of breast cancer (esp. at...
Genetics of ovarian cancer <ul><li>Genetic syndromes account for 10-15% of ovarian cancers </li></ul><ul><li>BRCA1 </li></...
Genetics <ul><li>Lynch syndrome II </li></ul><ul><ul><li>HNPCC (hereditary nonpolyposis colorectal cancer) </li></ul></ul>...
Symptoms <ul><li>Nonspecific </li></ul><ul><li>Lower abdominal discomfort, nausea, bloating, constipation, lower back pain...
Symptoms <ul><li>Paraneoplastic findings </li></ul><ul><ul><li>Hypercalcemia (particularly clear cell) </li></ul></ul><ul>...
Physical Exam <ul><li>Solid, fixed, irregular pelvic mass </li></ul><ul><li>Ascites </li></ul>
Work-up of Ovarian Mass <ul><li>Pelvic ultrasound  </li></ul><ul><li>CBC, LFTs </li></ul><ul><li>CT abdomen/pelvis </li></...
Tumor Markers <ul><li>CA-125  </li></ul><ul><ul><li>Elevated in 50% of stage I and 80-90% of stage II- IV tumors </li></ul...
Tumor Markers <ul><li> FP (alpha fetoprotein)- in germ cell tumors </li></ul><ul><li> -hCG (human chorionic gonadotropin...
Screening <ul><li>Routine CA-125 and endovaginal ultrasound not useful for screening of general population * </li></ul><ul...
Screening/prevention in high-risk patients <ul><li>BRCA-1 and BRCA-2 germline mutation </li></ul><ul><ul><li>prophylactic ...
Pathology From Up-to-date 3 main histological types Pap. (90%)
Psammoma Body From:  Indiana University Dept. of Pathology and Laboratory Medicine (erl.pathology.iupui.edu)
Staging for Epithelial Ovarian Cancer From:  Cannistra S. N Engl J Med 2004;351:2519-2529 I - Ovaries II - Pelvic viscera ...
Treatment <ul><li>Exploratory Laparotomy - Diagnosis, Staging and Treatment </li></ul><ul><ul><li>Goal:  Maximal debulking...
Surgery <ul><li>TAH/BSO </li></ul><ul><li>Visual examination of all peritoneal surfaces </li></ul><ul><li>Visual inspectio...
Surgical debulking of advanced disease <ul><li>Meta-analysis of 53 studies published 1989-1998 </li></ul><ul><li>Patients ...
Bristow, R. E. et al. J Clin Oncol 2002; 20:1248-1259.
Favorable Prognostic Factors <ul><li>Age (< 65) </li></ul><ul><li>Good performance status </li></ul><ul><li>Stage (I or II...
Adjuvant chemotherapy <ul><li>Standard chemo regimens </li></ul><ul><ul><li>Carboplatin(AUC 5-6)/paclitaxel (175mg/m2) q21...
Adjuvant Chemotherapy <ul><li>Cisplatin and carboplatin have equal efficacy in combination with paclitaxel * </li></ul><ul...
Alternative Adjuvant Chemo <ul><li>Platinum/cyclophosphamide </li></ul><ul><li>Doxorubin/cyclophosphamide  </li></ul><ul><...
Current controversies in chemo <ul><li>First-line intraperitoneal chemotherapy </li></ul><ul><li>Chemo in “high-risk” earl...
Intraperitoneal chemotherapy <ul><li>Rationale:  Since the peritoneal cavity is the principal site of disease, direct admi...
Phase III trials of intraperitoneal cisplatin/paclitaxel Alberts et al, NEJM 1996 Markman et al, JCO 2001 Armstrong et al,...
Intraperitoneal chemo <ul><li>Grade 3 and 4 toxicities more common in IP group </li></ul><ul><ul><ul><li>Pain, fatigue, my...
Chemo in “high-risk” early stage patients <ul><li>Stage IA or IB with grade 2 or 3, stage IC, stage IIA, stage I-IIA clear...
Copyright restrictions may apply. Trimbos, J. B. et al. J. Natl. Cancer Inst. 2003 95:113-125. Copyright restrictions may ...
Maintenance Chemotherapy <ul><li>Single-agent paclitaxel </li></ul><ul><ul><li>Enrolled women with complete response to pl...
Role of radiation <ul><li>No longer used as part of primary treatment in U.S. </li></ul><ul><ul><li>May be used in platinu...
Stage I <ul><li>Favorable prognostic factors (Stage IA and IB, grade 1 and ?2) </li></ul><ul><ul><li>Treat with surgery al...
Stage II <ul><li>Favorable prognostic factors </li></ul><ul><ul><li>Surgery then chemo (?3-4 cycles) </li></ul></ul><ul><l...
Stages III, IV <ul><li>Surgery then 6 cycles of chemo </li></ul><ul><ul><li>?Maintenance therapy - 12 cycles of paclitaxel...
Routine Monitoring <ul><li>>50% patients with surgery and chemo get complete CR (normal exam, CA125 and CT) </li></ul><ul>...
Recurrent/persistent disease <ul><li>Majority of patients with advanced disease relapse </li></ul><ul><li>Often see tumor ...
Treatment of asymptomatic recurrence <ul><li>Consider tamoxifen or aromatase inhibitor for patients with asymptomatic recu...
2nd Line Chemotherapy <ul><li>Usually single agent chemo </li></ul><ul><li>Clinical trial </li></ul><ul><li>Carbo/cis if p...
2nd line Chemotherapy (cont’d) <ul><li>Liposomal doxorubicin </li></ul><ul><li>Topotecan </li></ul><ul><li>Gemcitabine </l...
Biological agents <ul><li>Trials with VEGF and EGFR inhibitors in progress </li></ul><ul><ul><li>Newly-diagnosed disease <...
Summary <ul><li>Surgery is important for diagnosis, staging and treatment. </li></ul><ul><li>Surgery is initial treatment ...
Treatment of non-epithelial cancers <ul><li>Germ cell tumors - Surgery, then… </li></ul><ul><ul><li>Stage I dysgerminoma/S...
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  • PFS 16 mo for subopt. debulking/stage IV, 24 mo for opt. debulking
  • gopalan031607

    1. 1. Ovarian Cancer Priya Gopalan 3/16/07
    2. 2. Epidemiology <ul><li>8th most common cancer type in women (estimated 22,430 new cases ) </li></ul><ul><li>5th most common cause of cancer death in women (estimated 15,280 deaths ) </li></ul><ul><li>Average lifetime risk for women: 1 in 70 </li></ul><ul><li>Median age 60 </li></ul><ul><li>68% are metastatic at time of diagnosis </li></ul><ul><li>45% 5-yr survival rate for all stages (10-30% for metastatic disease) </li></ul><ul><li>From: Jemal et al., CA Cancer J Clin 2007; 57:43-66 </li></ul>
    3. 3. Risk factors <ul><li>Family history of ovarian/breast cancer </li></ul><ul><li>Personal history of breast cancer (esp. at young age) </li></ul><ul><li>Infertility/nulliparity/uninterrupted ovulation </li></ul><ul><ul><li>OCP use, pregnancy, lactation and tubal ligation reduce risk </li></ul></ul>
    4. 4. Genetics of ovarian cancer <ul><li>Genetic syndromes account for 10-15% of ovarian cancers </li></ul><ul><li>BRCA1 </li></ul><ul><ul><li>Germline mutation - in women, confers lifetime risk of: </li></ul></ul><ul><ul><ul><li>ovarian cancer: 16-44% </li></ul></ul></ul><ul><ul><ul><li>breast cancer: 56-87% </li></ul></ul></ul><ul><li>BRCA2 </li></ul><ul><ul><li>Germline mutation - in women, confers lifetime risk of: </li></ul></ul><ul><ul><ul><li>ovarian cancer: 10% </li></ul></ul></ul><ul><ul><ul><li>breast cancer: ~60-85% </li></ul></ul></ul>
    5. 5. Genetics <ul><li>Lynch syndrome II </li></ul><ul><ul><li>HNPCC (hereditary nonpolyposis colorectal cancer) </li></ul></ul><ul><ul><li>Also have endometrial, ovarian, GU, other GI cancers </li></ul></ul><ul><ul><li>Germline mutations in DNA mismatch repair genes, such as MSH2 or MLH1 </li></ul></ul>
    6. 6. Symptoms <ul><li>Nonspecific </li></ul><ul><li>Lower abdominal discomfort, nausea, bloating, constipation, lower back pain, fatigue </li></ul><ul><li>Abdominal fullness, increased abdominal girth, early satiety </li></ul><ul><li>Dyspnea </li></ul><ul><li>Pelvic pain </li></ul><ul><li>Sx of small bowel obstruction </li></ul><ul><li>Sx of urinary tract obstruction, hydronephrosis </li></ul>
    7. 7. Symptoms <ul><li>Paraneoplastic findings </li></ul><ul><ul><li>Hypercalcemia (particularly clear cell) </li></ul></ul><ul><ul><li>Subacute cerebellar degeneration </li></ul></ul><ul><ul><li>Trousseau’s syndrome </li></ul></ul><ul><ul><li>Sign of Leser-Trelat </li></ul></ul>
    8. 8. Physical Exam <ul><li>Solid, fixed, irregular pelvic mass </li></ul><ul><li>Ascites </li></ul>
    9. 9. Work-up of Ovarian Mass <ul><li>Pelvic ultrasound </li></ul><ul><li>CBC, LFTs </li></ul><ul><li>CT abdomen/pelvis </li></ul><ul><li>CXR </li></ul><ul><li>Tumor markers </li></ul><ul><li>NO NEEDLE BIOPSIES - risk of tumor spillage into peritoneal cavity </li></ul>
    10. 10. Tumor Markers <ul><li>CA-125 </li></ul><ul><ul><li>Elevated in 50% of stage I and 80-90% of stage II- IV tumors </li></ul></ul><ul><ul><li>Non-specific increase in benign ovarian tumors, fibroids, adenocarcinomas (e.g. breast) </li></ul></ul><ul><ul><li>Follow for efficacy of treatment, to detect recurrence </li></ul></ul><ul><li>CA 15-3 </li></ul>
    11. 11. Tumor Markers <ul><li> FP (alpha fetoprotein)- in germ cell tumors </li></ul><ul><li> -hCG (human chorionic gonadotropin)- in germ cell tumors </li></ul><ul><li>Inhibin - in stromal tumors </li></ul><ul><li>YKL-40 - secreted glycoprotein </li></ul><ul><ul><li>Elevated in 36/50 CA pts, while 23/50 had elevated CA125 (p<0.008)* </li></ul></ul>*Dupont JCO 2004
    12. 12. Screening <ul><li>Routine CA-125 and endovaginal ultrasound not useful for screening of general population * </li></ul><ul><ul><li>UK pilot study ** - 20,000 women- survival for those detected with ovarian CA: 73 mo (screened) vs. 43 mo (unscreened) </li></ul></ul><ul><ul><li>F/U study with 200,000 women - CA125 (then U/S) has PPV 21% </li></ul></ul><ul><ul><ul><li>OS? </li></ul></ul></ul>* NIH consensus conf. JAMA 1995 ** Jacobs et al., Lancet 1999
    13. 13. Screening/prevention in high-risk patients <ul><li>BRCA-1 and BRCA-2 germline mutation </li></ul><ul><ul><li>prophylactic BSO </li></ul></ul><ul><ul><ul><li>Also reduces risk of breast CA </li></ul></ul></ul><ul><ul><ul><li>Can still be at risk for primary peritoneal carcinoma </li></ul></ul></ul><ul><ul><li>oral contraceptives - controversial </li></ul></ul><ul><ul><li>close screening (not proven to be effective in high-risk patients) </li></ul></ul><ul><ul><ul><li>Frequent pelvic exams </li></ul></ul></ul><ul><ul><ul><li>CA125 q6-12 mo </li></ul></ul></ul><ul><ul><ul><li>Transvaginal Ultrasound q6-12 mo </li></ul></ul></ul><ul><li>HNPCC </li></ul><ul><ul><li>prophylactic TAH/BSO </li></ul></ul>
    14. 14. Pathology From Up-to-date 3 main histological types Pap. (90%)
    15. 15. Psammoma Body From: Indiana University Dept. of Pathology and Laboratory Medicine (erl.pathology.iupui.edu)
    16. 16. Staging for Epithelial Ovarian Cancer From: Cannistra S. N Engl J Med 2004;351:2519-2529 I - Ovaries II - Pelvic viscera III - Peritoneal implants, liver serosa, small bowel, omentum IV - Distant mets (liver parenchyma)
    17. 17. Treatment <ul><li>Exploratory Laparotomy - Diagnosis, Staging and Treatment </li></ul><ul><ul><li>Goal: Maximal debulking (try to remove all visible disease) </li></ul></ul><ul><ul><ul><li>Optimal debulking = No tumor mass > 1cm </li></ul></ul></ul><ul><ul><ul><li>Suboptimal debulking </li></ul></ul></ul><ul><ul><li>Follow GOG surgical protocol to definitively stage </li></ul></ul><ul><ul><li>Best done in an “expert center” </li></ul></ul>
    18. 18. Surgery <ul><li>TAH/BSO </li></ul><ul><li>Visual examination of all peritoneal surfaces </li></ul><ul><li>Visual inspection/palpation of liver </li></ul><ul><li>Omentectomy </li></ul><ul><li>Para-aortic lymph node biopsy </li></ul><ul><li>Peritoneal washings </li></ul><ul><li>Random biopsies of clinically uninvolved areas </li></ul>
    19. 19. Surgical debulking of advanced disease <ul><li>Meta-analysis of 53 studies published 1989-1998 </li></ul><ul><li>Patients were stages III/IV </li></ul><ul><li>Underwent initial cytoreduction (debulking), followed by platinum-based chemo </li></ul><ul><li>Maximal cytoreduction occurred if residual disease measured ≤ 3 cm in largest diameter </li></ul>Bristow RE et al. JCO 2002, 20:1248-59.
    20. 20. Bristow, R. E. et al. J Clin Oncol 2002; 20:1248-1259.
    21. 21. Favorable Prognostic Factors <ul><li>Age (< 65) </li></ul><ul><li>Good performance status </li></ul><ul><li>Stage (I or II) </li></ul><ul><li>No ascites </li></ul><ul><li>Optimal surgical debulking </li></ul><ul><li>Non-clear cell type </li></ul><ul><li>Well-differentiated (Grade I or II) </li></ul><ul><li>Diploid tumor (no aneuploidy) </li></ul><ul><li>Low post-op CA125 </li></ul>
    22. 22. Adjuvant chemotherapy <ul><li>Standard chemo regimens </li></ul><ul><ul><li>Carboplatin(AUC 5-6)/paclitaxel (175mg/m2) q21d x 6 cycles </li></ul></ul><ul><ul><li>Cisplatin (75mg/m2)/paclitaxel (135mg/m2) q21d x 6 cycles </li></ul></ul><ul><ul><li>Carboplatin (AUC 5-6)/docetaxel (60-75mg/m2) q21d x 6 cycles </li></ul></ul>*Ozols et al. JCO 2003, 21:3194-3200. **Vasey et al. JNCI 2004, 96:1682-91.
    23. 23. Adjuvant Chemotherapy <ul><li>Cisplatin and carboplatin have equal efficacy in combination with paclitaxel * </li></ul><ul><li>Paclitaxel and docetaxel have equal efficacy in combination with carboplatin ** </li></ul>*Ozols et al. JCO 2003, 21:3194-3200. **Vasey et al. JNCI 2004, 96:1682-91.
    24. 24. Alternative Adjuvant Chemo <ul><li>Platinum/cyclophosphamide </li></ul><ul><li>Doxorubin/cyclophosphamide </li></ul><ul><li>3-drug combinations </li></ul><ul><ul><li>Two phase III trials comparing 3 drugs to carbo/taxol showed no additional benefit (Bookman ASCO 2006, Scarfone ASCO 2006) </li></ul></ul>
    25. 25. Current controversies in chemo <ul><li>First-line intraperitoneal chemotherapy </li></ul><ul><li>Chemo in “high-risk” early stage disease </li></ul><ul><li>Maintenance chemotherapy </li></ul>
    26. 26. Intraperitoneal chemotherapy <ul><li>Rationale: Since the peritoneal cavity is the principal site of disease, direct administration of chemo into the peritoneum will permit exposure to high concentrations of chemo for a prolonged period of time, while reducing generalized toxicities from intravenous administration. </li></ul>
    27. 27. Phase III trials of intraperitoneal cisplatin/paclitaxel Alberts et al, NEJM 1996 Markman et al, JCO 2001 Armstrong et al, NEJM 2006 IV taxol + IP cis, IP taxol on d8 IV carbo x 2, IV taxol + IP cis IV cytoxan + IP cis Chemo-study 42% got 6 IP (41% ≤ 2 IP) IV:50 mo IP:66 mo (p=0.03) IV:18 mo IP:24 mo (p=0.05) IV taxol + IV cis Armstrong 18% ≤ 2 IP IV:52 mo IP:63 mo (p=0.05) IV:22 mo IP:28 mo (p=0.01) IV taxol + IV cis Markman 18% ≤ 2 IP IV:41 mo IP:49 mo (p=0.02) --- IV cytoxan + IV cis Alberts %receiving IP OS PFS Chemo-control Trial
    28. 28. Intraperitoneal chemo <ul><li>Grade 3 and 4 toxicities more common in IP group </li></ul><ul><ul><ul><li>Pain, fatigue, myelotoxicity, GI, neurologic </li></ul></ul></ul><ul><ul><ul><li>Quality of life worse in IP group during and immediately after treatment, but equivalent at one year </li></ul></ul></ul><ul><li>Rec: Consider in women with stage III tumor and small-volume residual disease after maximal debulking </li></ul><ul><ul><li>Taxol 135 mg/m2 IV + Cis 100mg/m2 IP + (day 8) Taxol 60mg/m2 IP </li></ul></ul>
    29. 29. Chemo in “high-risk” early stage patients <ul><li>Stage IA or IB with grade 2 or 3, stage IC, stage IIA, stage I-IIA clear-cell </li></ul><ul><li>ICON1 trial and EORTC-ACTION trial </li></ul><ul><ul><li>After surgery, randomized to platinum-based chemo or observation </li></ul></ul><ul><ul><li>ACTION trial had strict guidelines on patient eligibility, surgical staging and chemo </li></ul></ul><ul><ul><li>Improved PFS and OS with chemo </li></ul></ul><ul><ul><li>Most effective in suboptimally debulked patients </li></ul></ul>ICON1. JNCI, 2003, 95:125-32. Trimbos et al. JNCI, 2003, 95:113-124.
    30. 30. Copyright restrictions may apply. Trimbos, J. B. et al. J. Natl. Cancer Inst. 2003 95:113-125. Copyright restrictions may apply. OS, optim. debulked OS, suboptim. debulked RFS, optim. debulked RFS, suboptim. debulked * *
    31. 31. Maintenance Chemotherapy <ul><li>Single-agent paclitaxel </li></ul><ul><ul><li>Enrolled women with complete response to platinum/paclitaxel combination - 262 evaluable </li></ul></ul><ul><ul><li>Received 3 vs. 12 additional cycles of paclitaxel (175 mg/m2) q28d </li></ul></ul><ul><ul><li>Closed early because of significant diff. in PFS (21 for 3 cycles vs. 28 months for 12 cycles, p=0.0023) </li></ul></ul><ul><ul><ul><li>No difference in OS at time of study closure </li></ul></ul></ul><ul><li>Rec: Discuss results of this trial and give pt. option of receiving maintenance paclitaxel </li></ul>Markman et al. JCO 2003, 21:2460-65.
    32. 32. Role of radiation <ul><li>No longer used as part of primary treatment in U.S. </li></ul><ul><ul><li>May be used in platinum-resistant disease </li></ul></ul><ul><li>Occasionally used for large pelvic recurrences, brain and bone mets </li></ul><ul><li>NCCN guidelines: option for microscopic Stage III disease (category 3 recommendation) </li></ul>
    33. 33. Stage I <ul><li>Favorable prognostic factors (Stage IA and IB, grade 1 and ?2) </li></ul><ul><ul><li>Treat with surgery alone (5-yr. survival 90-95%) </li></ul></ul><ul><li>Unfavorable prognostic factors (grade ?2 and 3, stage IC) </li></ul><ul><ul><li>Surgery then 6 cycles of chemo </li></ul></ul>
    34. 34. Stage II <ul><li>Favorable prognostic factors </li></ul><ul><ul><li>Surgery then chemo (?3-4 cycles) </li></ul></ul><ul><li>Unfavorable prognostic factors </li></ul><ul><ul><li>Surgery then 6 cycles of chemo </li></ul></ul>
    35. 35. Stages III, IV <ul><li>Surgery then 6 cycles of chemo </li></ul><ul><ul><li>?Maintenance therapy - 12 cycles of paclitaxel </li></ul></ul>
    36. 36. Routine Monitoring <ul><li>>50% patients with surgery and chemo get complete CR (normal exam, CA125 and CT) </li></ul><ul><li>Monitor with exams and CA125 </li></ul><ul><li>Use of “second-look” laparotomy not supported (Ozols JCO 2003) </li></ul>
    37. 37. Recurrent/persistent disease <ul><li>Majority of patients with advanced disease relapse </li></ul><ul><li>Often see tumor marker increase ~ 3 months before clinical/radiological detection </li></ul><ul><li>“ Secondary cytoreduction” might be helpful in patients with >6-12 month first remission (Hoskins Gynecol Oncol 1989) </li></ul><ul><li>Usually responds to series of different chemo regiments </li></ul><ul><ul><li>Response rate to each drug 10-20% </li></ul></ul><ul><ul><li>Can see 5-10 yr. survivals after recurrence, with good quality of life </li></ul></ul>
    38. 38. Treatment of asymptomatic recurrence <ul><li>Consider tamoxifen or aromatase inhibitor for patients with asymptomatic recurrence (tumor marker-only recurrence) </li></ul><ul><ul><li>Markman M et al. Gynecol Oncol 1996; Bowman et al. Clin Cancer Res 2002) </li></ul></ul><ul><ul><li>Fewer than 20% have response to hormonal therapy, but occ. see marked decrease in CA125 and prolonged stable disease </li></ul></ul>
    39. 39. 2nd Line Chemotherapy <ul><li>Usually single agent chemo </li></ul><ul><li>Clinical trial </li></ul><ul><li>Carbo/cis if platinum-sensitive (≥ 6 months since last dose) </li></ul><ul><ul><li>Response rate ≥ 30% (Cannistra et al. JCO 2002) </li></ul></ul><ul><ul><li>>60% response rate if ≥ 2 years since prior treatment (Cannistra et al. JCO 2002, Markman et al. JCO 1991) </li></ul></ul><ul><ul><li>Add taxol, if taxane-sensitive </li></ul></ul>
    40. 40. 2nd line Chemotherapy (cont’d) <ul><li>Liposomal doxorubicin </li></ul><ul><li>Topotecan </li></ul><ul><li>Gemcitabine </li></ul><ul><li>Taxotere, paclitaxel </li></ul><ul><li>5-FU </li></ul><ul><li>Oral etoposide </li></ul><ul><li>Vinorelbine </li></ul><ul><li>Hexamethylmelamine (alkylating agent) </li></ul>
    41. 41. Biological agents <ul><li>Trials with VEGF and EGFR inhibitors in progress </li></ul><ul><ul><li>Newly-diagnosed disease </li></ul></ul><ul><ul><li>Tumor marker-only relapse </li></ul></ul><ul><ul><li>Several phase II trials with bevacizumab as 2+ line therapy in advanced disease </li></ul></ul>
    42. 42. Summary <ul><li>Surgery is important for diagnosis, staging and treatment. </li></ul><ul><li>Surgery is initial treatment for all stages (even metastatic). </li></ul><ul><li>Platinum/taxane combinations are standard regimen, usually for 6 weeks. </li></ul><ul><li>“ High risk” early stage disease benefits from chemo if suboptimally debulked. </li></ul><ul><li>Intraperitoneal chemotherapy is beneficial, and used routinely for stage III patients. </li></ul>
    43. 43. Treatment of non-epithelial cancers <ul><li>Germ cell tumors - Surgery, then… </li></ul><ul><ul><li>Stage I dysgerminoma/Stage I (Grade 1) immature teratoma - OBSERVE </li></ul></ul><ul><ul><li>Everything else - CHEMO (BEP = Bleo, Etoposide, Cis) </li></ul></ul><ul><li>Stromal tumors - Surgery, then… </li></ul><ul><ul><li>Stage I low risk - OBSERVE </li></ul></ul><ul><ul><li>Stage I high risk (Stage IC or grade 3) - Observe or cis-based chemo or RT </li></ul></ul><ul><ul><li>Stage II-IV - </li></ul></ul><ul><ul><ul><li>Limited disease - RT </li></ul></ul></ul><ul><ul><ul><li>Otherwise, platinum-based chemo (BEP or carbo/taxol or etoposide/carbo ± doxorubicin) </li></ul></ul></ul>

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