Ovarian cancer surgery march 2012

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Ovarian cancer surgery march 2012

  1. 1. OPTIMAL SURGICAL MANAGEMENT OF OVARIAN CANCER March 2012 Prafull Ghatage Gynecologic Oncologist Tom Baker Cancer Centre Calgary, CANADA.
  2. 2. Learning objectives •  Pelvic Masses – assessment •  Epidemiology / Etiology •  Recent trends in surgical management •  Recurrent cancer management •  Palliative surgery
  3. 3. Approach to Pelvic Mass Pelvic Mass Non-gynecologic Gynecologic Bowel, bladder, kidney Soft tissues, other Pregnancy Non-Pregnancy Ovary Fallopian Tube Uterus Benign or Malignant Benign or Malignant Benign or Malignant
  4. 4. Pregnancy related masses •  Theca Luteal cyst •  Luteoma
  5. 5. Benign Ovarian Cysts/Tumors •  Functional •  Endometriotic cysts •  Polycystic ovarian syndrome •  Tubo-ovarian abscess •  Cystic or mature teratoma •  Fibroma / Thecoma
  6. 6. ACOG Guidelines •  Ova 1 assay – Ca125 / Apolipoprotein / B2 microglobulin / Transthyretin / Transferin •  Ca 125 •  Abdominal metastasis •  Fixed or nodular pelvic mass •  Family history
  7. 7. Serum H4 in Ovarian cancer •  Over-expressed in early ovarian cancer •  Combination of Ca 125 and H4 increases sensitivity
  8. 8. Risk of Malignancy Index Ultrasound features Risk of Malignancy Score Multilocular cyst Solid elements Bilaterality Ascites Intra-abdominal metastasis Premenopausal Postmenopausal Ca125 1= none or 1 abnormality 2= 4 or more abnormalities 1 4 U/ml Positive predictive Value-80% Specificity 90%
  9. 9. Histology- Malignant Ovarian Tumors •  65 % epithelial •  20 % germ cell •  10 % stromal •  5% metastatic (uterus,GI, breast)
  10. 10. Epithelial ovarian cancer - Epidemiology •  27,000 new cases a year in the US / 2,400 new cases in Canada –  4% of cancer in women •  15,000 deaths in the US / 1,500 deaths in Canada •  Rising incidence (now 1/57 ♀) with over 50% > 65 years of age •  75% Advanced at diagnosis •  Overall Five-year survival: 25–40% overall –  Advanced stage: 30 % Most will develop recurrent disease and are NOT curative
  11. 11. FEMALES 3491 Breast 783 Thyroid 328 Colo-rectal 281 NHL 224 Leukemia 194 Uterus 117 Ovary 108 Saudi Registry 2004
  12. 12. Age related risk of Ovarian Cancer 20-44 years 7/100,000 45-64 years 27/100,000 65-74 years 70/100,000 > 75 years 145/100,000
  13. 13. Ovarian cancer •  25 % early •  75 % advanced 5 Year Survival < 40 % Stage 5 yr survival IA-B 90% IC 80% II-IIIA 55-65% IIIB-C 30% IV < 20%
  14. 14. Etiology •  cause unknown •  protective factors: –  number of pregnancies –  breast-feeding –  BCP –  tubal ligation – increased protection with salpingectomy –  hysterectomy
  15. 15. Etiology •  risk factors: –  early menarche/late menopause –  ? obesity –  demographic –  age •  family history - 90% sporadic - 10% hereditary
  16. 16. Surveillance for hereditary ovarian cancer BRCA I and BRCA II •  PV yearly (start 5yrs earlier then youngest relative diagnosed with ovarian cancer) •  US yearly •  CA125 if > 50 – 9% chance of cancer if > 100 – 15% chance of cancer •  BCP 50% risk reduction in BRCA mutation carriers •  BSO 90% reduction in risk of ovarian cancer 50% reduction in risk of subsequent breast cancer •  TL 60% risk reduction in BRCA mutation carriers
  17. 17. Hereditary ovarian cancer HNPCC lifetime risk for developing endometrial and ovarian cancer is substantially increased: •  80% CRC •  50% endometrial •  13% stomach •  12% ovarian •  4% GU TCC •  4% brain •  small intestine, liver and biliary tract NB: if 1 cancer develops, 25% chance of 2nd cancer
  18. 18. Surveillance for hereditary ovarian cancer HNPCC •  screen annually for uterine ca from age 35 •  Cox2 inhibitors •  TAH/BSO
  19. 19. SCREENING Ineffective
  20. 20. UKCTOS / PLCO •  35 surgeries per invasive cancer / 31 surgeries per invasive cancer •  80% advanced stage •  Screening did NOT change expected stage distribution from an unscreened population Lancet Oncol, 2009 Obstet Gyecol, 2009
  21. 21. Role of Surgery •  Diagnosis •  Early disease – comprehensive staging •  Advanced disease – primary cytoreduction •  Secondary cytoreduction •  Palliative Surgery
  22. 22. Surgery for Early Ovarian Cancer •  includes pelvic nodes, para-aortic nodes, infracolic omentectomy, multiple biopsies •  Appendectomy in all mucinous tumors. Consider also in all epithelial tumors if suspicious of disease 30 % of patients upstaged – hence impact on survival
  23. 23. Staging procedure if fertility sparing required •  Preserve contralateral ovary and uterus •  Comprehensive staging – infracolic omentectomy, pelvic nodes, para-aortic nodes, peritoneal biopsies still required
  24. 24. Upstaging of a clinical Stage I cancer •  Positive cytology 20% •  Omentum 6% •  Diaphragm 15% •  Peritoneal biopsies 13% •  Para-aortic nodes 14% •  Pelvic nodes 6% JB Trimblos, Int J gyne cancer,2000
  25. 25. Serous Tumors
  26. 26. Mucinous Tumors
  27. 27. Papillary Serous Cystadenoma ? carcinoma
  28. 28. Papillary Serous Cystadenoma?carcinoma
  29. 29. Ovarian Cancer: Staging by Surgical Specialty Evaluation of completeness of surgical staging Nearly half of women with early ovarian cancer were inadequately staged by general Ob/ Gyns or General Surgeons Surgeon Complete Staging Gyn/Onc 97% Ob/Gyn 52% Surgeon 35% Source: McGowen et al. Ob/Gyn 1985.Junor et al,BJOG 1999
  30. 30. Case Presentation •  70 year old •  6 month history of –  increased abdominal girth –  weakness –  weight loss •  ascites •  complex pelvic mass
  31. 31. PERITONEAL     CARCINOMATOSIS  
  32. 32. OMENTAL  CAKE   ASCITES  
  33. 33. Survival influenced by: •  stage •  grade •  histologic type •  completeness of cytoreduction other favourable prognostic factors: •  younger age •  good performance status •  smaller disease volume prior to any surgical cytoreduction •  absence of ascites
  34. 34. Theoretical Benefits of Cytoreductive Surgery for Advanced Otaviran Carcinoma • Removal of large bulky tumors with poor blood supply • Improved sensitivity of residual masses to postoperative chemotherapy • Greater likelihood of tumor eradication before chemoresistance develops
  35. 35. cytoreductive surgery is critical Cytoreduction 5 yr OS micro residual 60 – 75 % macro residual < 2cm 40% > 2cm 15%
  36. 36. Cytoreductive Surgery meta-analysis •  each 10 % increase in maximal cytoreduction associated with 4.1% increase in median survival time •  gyn oncologists – OR – 25% reduction in death compared to generalists in advanced cancers ( P = 0.005 )
  37. 37. Bristol et al. J Clin Oncol 2002 Meta-Analysis (N=6,885)
  38. 38. Survival by Residual Disease
  39. 39. Ovarian Cancer: Survival by Residual Disease GOG Protocols (PR) 52 and 97
  40. 40. Surgical Procedures to Achieve Optimal Cytoreduction in Advanced Ovarian Carcinoma • TAH / BSO/ infracolic omentectomy + extensive lymph node dissection + extensive bowel resection + resection of liver capsule + supracolic omentectomy, + diaphragm stripping, + splenectomy + porta hepatis + gall bladder
  41. 41. Splenectomy
  42. 42. Is Less Than 1 cm Residual the Best Cutoff Point for Optimal Cytoreduction? As data accumulates, it is becoming increasingly clear that even among optimally resected patients, extended survival rates are associated with debulking of all visible disease Median progression-free survival: - No gross residual: 22 months - Gross 0.1-1.0 cm: 12 months - Gross > 1.0 cm: 6 months Bristow and Montz. Gynecol Oncol 2001
  43. 43. Median Survival by Residual Disease Chi DS et al. Gynecol Oncol 2006 Residual Disease No. Patients Median Survival No gross 57 81 months Gross <0.5 cm 51 56 months Gross 0.5 – 1.0 cm 92 47 months Gross 1 – 2 cm 53 31 months Gross > 2 cm 172 34 months
  44. 44. Role of neoadjuvant chemotherapy in advanced ovarian cancer
  45. 45. Randomised EORTC-GCG / NCIC-CTG trial on NACT + IDS versus PDS Study conduct • Between September 1998 and December 2006, 718 patients were randomised in 60 institutions (range: 1 – 125 patients). • 498 events were needed to perform the final analysis, and were reached in August 2008 • Median follow-up was 4.8 years.
  46. 46. Neo-adjuvant Chemotherapy in advanced ovarian cancer Ovarian tubal or peritonal cancer FIGO stage IIIC and IV (n = 720) Randomisation Upfront Debulking Surgery Neoadjuvant chemotherapy 3 x Platinum based CT 3 x Platinum based CT Interval debulking (not obligatory) Interval debulking If no PD > 3 x Platinum based CT > 3 x Platinum based CT Primary Endpoint : Survival Secondary endpoints: Progression Free Survival, Quality of Life, Complications
  47. 47. Randomised EORTC-GCG/NCIC-CTG trial on NACT + IDS versus PDS < 1 cm residual per country (PP1) Total PDS ( n = 329) NACT -> IDS (n = 339) * Belgium (n = 133) 83% 72% 94% Argentina (n = 48) 71% 68% 74% The Netherlands (n = 104) 59% 40% 77% Sweden (n = 23) 59% 40% 75% Norway (n = 82) 55% 35% 73% Italy ( n=38) 52% 40% 64% Spain (n = 62) 49% 44% 58% UK (n = 101) 47% 37% 63% Canada (n = 84) 44% 29% 59%
  48. 48. Randomised EORTC-GCG/NCIC-CTG trial on NACT + IDS versus PDS Surgical findings and results (PP1) PDS (n = 329) NACT -> IDS (n = 339)* Metastases before > 2cm 95% 68% Metastases before > 10cm 62% 27% No residual after surgery 21% 53% < 1cm after surgery 46% 82% * % calculated on the 306 patients who underwent IDS
  49. 49. Randomised EORTC-GCG/NCIC-CTG trial on NACT + IDS versus PDS Surgical characteristics (PP1) PDS (n = 329) NACT -> IDS (n = 339)* Postoperative mortality (< 28 days) 2.7% 0.6% Postoperative sepsis 8% 2% Fistula (bowel/GU) 1,2% / 0,3% 0,3% / 0,6% Operative time (minutes) 180 180 Red blood cell transfusion 51% 53% Hemorhage Grade 3/4 7% 1% Venous Gr ¾ 2.4% 0,3% * % calculated on the 306 patients who underwent IDS
  50. 50. NACT + IDS versus PDS: ITT
  51. 51. NACT + IDS versus PDS: ITT
  52. 52. Gynecologic Cancer Intergroup - 2010 •  Surgical staging should be mandatory and be performed by a gynecologic oncologist •  The term optimal cytoreduction should be reserved for those with no macroscopic residual disease •  Delayed primary surgery following neoadjuvant chemotherapy is an option for selected patients with stage IIIC and IV ovarian cancer
  53. 53. Advantages of neoadjuvant chemotherapy followed by IDS •  Decrease in morbidity and mortality •  Advantage in advanced cancer
  54. 54. Secondary Cytoreduction for Recurrent Ovarian Cancer
  55. 55. Secondary Cytoreductive Surgery in Patientss With Platinum-Sensitive Disease Chi DS, et al. Cancer. 2006;106:1933-1939.     DFI Single Site Multiple Sites: No Carcinomatosis Carcinomatosis 6-12 mos Offer SC Consider SC No SC 12-30 mos Offer SC Offer SC Consider SC > 30 mos Offer SC Offer SC Offer SC
  56. 56.                            Harter  P,  et  al.  Ann  Surg  Oncol.  2006;13:1702-­‐1710   Combina@on  of  PS,  early  FIGO  stage  ini@ally  or  no  residual  tumor  aHer  first  surgery,  and  absence  of   ascites  could  predict  complete  resec@on  in  79%  of  pts   DESKTOP-OVAR: Predictors of Successful Surgery (= Complete Resection) Multivariate Analysis Pre-Op Variable OR 95% CI P Value PS (ECOG 0vs > 0) 2.65 1.56-4.52 < .001 Residual disease 1st surgery (0 vs > 0) 2.46 1.45-4.20 < .001 Or initial FIGO stage (I/II vs III/IV) 1.87 1.04-3.37 .036 No ascites (cutoff 500 mL) 5.08 1.97-13.16 < .001
  57. 57. Surgery in Recurrent disease - Harter et al,IJGC,2009
  58. 58. A  randomized  trial  evalua@ng  cytoreduc@ve  surgery  in  pts  with     pla@num-­‐sensi@ve  recurrent  ovarian  cancer   Pla@num-­‐sensi@ve   recurrent  cancer  of  the   ovaries,  fallopian  tubes,  or   peritoneum   PFI  >  6  mos   No  previous  chemotherapy   for  this  1st  relapse   Complete  resec@on   seems  feasible  and  posi@ve     AGO  score:   §   ECOG  PS  0   §   No  ascites  >  500  mL   §   Previous  complete  debulking   or  ini@al  FIGO  I/II      (if  data  available)   R A N D O M I Z E Cytoreduc@ve   surgery   Pla@num-­‐based   chemotherapy*   recommended   *   No  surgery   AGO-OVAR DESKTOP III
  59. 59. GOG-213
  60. 60. Role of Secondary Cytoreduction Gynecologic Cancer Intergroup Consensus Conference 2010 • Surgery appropriate in select patients • No level I evidence of benefit • However, it may be of benefit if optimal cytoreduction
  61. 61. Palliative Surgery
  62. 62. Palliative Surgery •  Paracentesis including indwelling abdominal catheter – eg Tenkhoff catheter •  Thoracocentesis / Pleurodesis /Permanent indwelling catheter eg Pleurex •  Nephrostomy/ureteric stents •  Gastrostomy tube •  GI stents •  Surgery to relieve bowel obstruction
  63. 63. Tumor ileus
  64. 64. Surgery to relieve bowel obstruction Only useful if a mass is causing the obstruction. Usually the obstruction is due to a tumor ileus
  65. 65. Options for bowel obstruction due to a mass •  Bowel resection with anastamosis •  Bypass surgery •  Colostomy / mucous fistula •  Ileostomy / mucous fistula
  66. 66. Conclusions •  Early clinical stage- 30% upstaged •  Advanced stage- cytoreduction critical for better survival •  Role for neoadjuvant chemotherapy in advanced cancer •  Role for secondary cytoreduction in select patients •  Role for palliative surgery

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