Optimal Surgery for Ovarian and Endometrial Cancers Jason Dodge, MD, FRCSC, MEd May 11 th, 2012

Objectives At the end of this session, participants will be able to… list the rationales for the surgical management of endometrial and ovarian cancers recognize the optimal components of surgical staging for both endometrial and ovarian cancers understand the importance of surgical staging for endometrial and ovarian cancer in determining prognosis and the role(s) for adjuvant therapy identify the importance of surgical debulking for ovarian cancer

OVARIAN CANCER

Prototype Case 52 y.o. G 3 P 3 post-menopausal woman Healthy, asymptomatic 7-8 cm pelvic mass on routine exam U/S – 7.5 cm multiloculated, solid/cystic mass arising within right ovary CA-125 – 25 Booked for surgery by community gynaecologist

Prototype Case TAH-BSO through lower transverse incision Solid/cystic ovarian mass resected intact No other abnormalities identified in OR note Final pathology: –Grade 2 serous carcinoma of ovary –Negative uterus and contralateral adnexa

What stage is this woman’s ovarian cancer? a)1A b)1B c)1C d)2B e)3C

What is the risk this woman has (undetected) metastatic disease? a)<1% b)10% c)30% d)50% e)80% Young et al., JAMA, 1983

What is the best approach to her management at this point? a)Observation b)Refer back to local gynaecologist for repeat surgery for optimal surgical staging c)Refer to Gynaecologic oncologist for repeat surgery for optimal surgical staging d)Adjuvant chemotherapy (Carbo/Taxol IV) e)Other

Outline Optimal surgery for ovarian cancer –Diagnosis –Surgical Staging –Debulking –Facilitating optimal treatment

Roles of Primary Surgery in Ovarian Cancer Diagnosis (final) Staging (SURGICAL, NOT CT!) Therapy –Palliation of symptoms –Removal of cancer (debulking) Facilitating optimal adjuvant therapy –Prognosis of individual patient –Risks/benefits of adjuvant therapy

Surgery in Ovarian Cancer: Staging Patterns of spread: Intraperitoneal Local Lymphatic Hematogenous Optimal surgical staging procedure must rule out metastases by all of these routes

Surgery in Ovarian Cancer: Staging Components of optimal surgical staging: Peritoneal washings Inspection and palpation of abdominal and pelvic organs and peritoneal surfaces –biopsy of all suspicious lesions BSO (+/- TAH) Omentectomy Pelvic & para-aortic lymphadenectomies Multiple peritoneal biopsies

13 FIGO staging (ovary) I – confined to ovary/ies –A (single ovary) –B (bilateral ovaries) –C (positive washings, surface disease, ruptured) II – confined to pelvis –A (fallopian tube or uterine extension) –B (other pelvic metastases) –C (pelvic involvement with +washings or tumour rupture) III – abdominal/pelvic cavity extension or nodes +ve –A (microscopic only) –B (<2 cm nodule(s)) –C (>2cm nodule(s) or retroperitoneal lymph nodes involved) IV – positive pleural effusion, parenchymal liver or other distant metastases

What stage is this woman’s ovarian cancer? a)1A b)1B c)1C d)2B e)3C ?

KEY MESSAGE! What is the risk this woman has (undetected) metastatic disease? a)<1% b)10% c)30% d)50% e)80% Young et al., JAMA, 1983

Surgery in Ovarian Cancer: Staging “Stage 1” patients who are not optimally staged at surgery have a poorer survival! ACTION trial Trimbos et al., JNCI, 2003

Surgery in Ovarian Cancer: Staging No benefit to adjuvant chemoRx in patients who are optimally surgically staged! ACTION trial Trimbos et al., JNCI, 2003

Surgery in Ovarian Cancer: Debulking Optimal debulking of metastatic disease associated with improved survival –Best predictor of survival in patients with advanced stage disease –Delay in definitive surgical debulking may be associated with decreased survival Bristow et al., J Clin Oncol, 2002 Bristow & Chi, Gynecol Oncol, 2006

Therapeutic Debulking Bristow et al., JCO, 2002

Surgery in Ovarian Cancer: Facilitating Optimal Adjuvant Therapy “Stage I” –If optimally staged, evidence suggests that chemotherapy may not be useful in improving survival –If not optimally staged, chemotherapy indicated to improve survival rates (because significant number have undiagnosed advanced staged disease) ICON1/ACTION trials Trimbos et al., JNCI, 2003

Surgery in Ovarian Cancer: Facilitating Optimal Adjuvant Therapy Advanced Stage –Chemotherapy demonstrated to improve overall survival –Recent acceptance of intraperitoneal chemotherapy as ideal mode of therapy for women with optimally debulked disease after primary surgery Optimal debulking <1 cm residual Insertion of IP catheter at primary surgery Armstrong et al., NEJM, 2006 Covens et al., CCO Guidelines, 2005

Surgery in Ovarian Cancer: Intraperitoneal Chemotherapy Delivery of chemotherapy directly into peritoneal cavity via implanted catheter Most pronounced survival benefit ever documented in ovarian cancer (17 m) Only patients optimally debulked at primary surgery are eligible Armstrong et al., NEJM, 2006

Current practice in Ontario… Many ovarian cancer surgery cases in Ontario are not performed optimally Many women with high pre-operative likelihood of ovarian cancer in Ontario would not be referred to a gynaecologic oncologist prior to surgery Dodge, JOGC, 2007 Elit et al., JOGC, 2006

Role of Gyn Oncology Referral Women with ovarian cancer who have primary surgery performed by a gynaecologic oncologist [at a tertiary centre] have a better outcome (survival) –More likely to be optimally staged –More likely to be optimally debulked –More likely to receive optimal adjuvant therapy Elit et al., JOGC, 2006 Giede et al., Gynecol Oncol., 2005 Le et al., JOGC, 2009

Early Stage Ovarian Cancer N PopulationQuestionMeasurementResults Puls Texas Stage 1Gyne onc vs community gyne 6 yr survival 90% vs 68% ( p=0.04) Mayer Conneticut Stage 1 & 2Gyne onc vs non onc 5 yr survival 83% vs 76% (p<0.05) Grossi Gyne onc vs non onc Staging lap adequate 47% vs 15% (p< 0.001) Le Saskatchewan 2002 Early stageMinimal staging vs comprehensive staging Recurrence OR 2.62 favouring comprehensive

Advanced Ovarian Cancer NPopulationQuestionOutcomeResults Eisenkop Stage 3C & 4 Gyne onc vs non onc survival35vs 17% (p<0.0001) Carney All UtahGyne onc vs non onc 5 yr survival26 vs 15 mos (p<.01) Junor All ScotlandGyne onc vs non onc Survival25 % death reduction Tingulstad All stagesGyne onc vs non onc Survival21 vs 12 mos (p=0.01) Engelen All stagesGyne onc vs non onc Survival Stages 1-2 Stages % vs 70% 21% vs 13% (p=0.03) Elit 2006OntarioHigh volume vs low volume SurvivalHigher volume better outcome

“Women with a high likelihood of having ovarian cancer should ideally be referred to a gynaecologic oncologist preoperatively to facilitate optimal surgery for ovarian cancer.” CCO Quality Indicators - Gagliardi et al., Gynecol Oncol, 2006 SOGC Guidelines – Le et al., JOGC, 2009 SGO Referral Guidelines, Gynecol Oncol, 2000 ACOG Committee Opinion #280, December, 2002

ENDOMETRIAL CANCER

Prototype Case 61 y.o. G 0 P 0 post-menopausal woman Healthy, bleeding x few weeks No abnormality detected on routine exam Endometrial biopsy reveals grade 3 endometrioid adenocarcinoma of uterus Booked for surgery by community gynaecologist

Prototype Case TAH-BSO through lower transverse incision No other abnormalities identified in OR note Final pathology: –Serous carcinoma of uterus –No myometrial invasion, no LVSI/CLS –Negative cervix and adnexa

What is the risk this woman has (undetected) metastatic disease? a)<1% b)10% c)25% d)50% e)80%

What is the next best step in her management? a)Observation b)Refer to Gynaecologic oncologist for repeat surgery for optimal surgical staging c)Adjuvant chemotherapy (Carbo/Taxol IV) d)Adjuvant radiotherapy e)Other

Roles of Primary Surgery in Endometrial Cancer Diagnosis (final) Staging (SURGICAL, NOT CT!) Therapy –Palliation of symptoms –Removal of cancer (debulking) Facilitating optimal adjuvant therapy –Prognosis of individual patient –Risks/benefits of adjuvant therapy

Surgery in Endometrial Cancer: Staging Patterns of spread: Local Lymphatic Intraperitoneal Hematogenous Optimal surgical staging procedure must rule out metastases by all of these routes

Surgery in Endometrial Cancer: Staging Components of optimal surgical staging: Peritoneal washings Inspection and palpation of abdominal and pelvic organs and peritoneal surfaces –biopsy of all suspicious lesions BSO (+/- TH) “extended” surgical staging –Omentectomy and peritoneal biopsies –Pelvic & para-aortic lymphadenectomies

Staging for Endometrial Carcinoma FIGO 1971 Clinical Staging FIGO 1988 Surgical Staging GOG 33, 1987

Surgical staging: Findings GOG 33 (n=621) – “clinical stage I” exploratory laparotomy, TAH-BSO, pelvic & para-aortic nodes, peritoneal washings –positive peritoneal washings 12% –positive adnexa 5% –positive pelvic nodes 9% –positive aortic nodes 6% –intraperitoneal disease 6% 22% ADVANCED STAGE DISEASE22% ADVANCED STAGE DISEASE

Pelvic lymph node metastases GOG 33, 1987

Para-aortic lymph node metastases GOG 33, 1987

FIGO staging (endometrium)

Benefits of Pelvic Lymphadenectomy Documentation of true nodal status (prognostic) –usually only microscopic involvement (~90%) –worse prognosis when +ve (50-70% 5-yr OS with Rx) Randall, 2006 Muggia, 2007 Randall, 2006 Muggia, 2007

Benefits of Pelvic Lymphadenectomy Therapeutic value –Benefit from chemotherapy +/- RRx if nodes involved –Avoidance of whole pelvic RRx if staging negative –? Independent survival benefit MRC, Italian trial vs. Kilgore, Fanning, Orr, MRC, Italian trial vs. Kilgore, Fanning, Orr, Randall, 2006 Muggia, 2007 Randall, 2006 Muggia, 2007 PORTEC, EN-5, MRC, GOG 99, NRH

Para-aortic lymphadenectomy Higher potential for morbidity Prolonged operative time Most cases (98%) can be predicted based on: –+ve pelvic nodes, OR –+ve adnexa, OR –+ve cervix Potential benefit small Faught, 1994 GOG 33, 1987

What are the risks? Improved with training (Gyn Onc) These risks not solely due to nodes Much of this risk related to para-aortic node dissection Much improved with laparoscopy (Lap-2) Blood loss > 1 litre 1% GI injury2% GU injury0.5% Vascular injury4% Ileus10% Thrombosis2% Fistula1% Death0.5% GOG LAP-2,2006

Perspective from Other Pelvic Cancers Adjuvant chemotherapy proven survival benefit in node-positive colorectal cancer  mesorectal excision (node dissection) Adjuvant chemotherapy proven survival benefit in node-positive cervical cancer Risk of pelvic node metastases in cervical cancer managed surgically at PMH: 5%

Current Use of Lymphadenectomy for Endometrial Cancer in Toronto NOT ROUTINE SELECTIVE SAMPLINGSELECTIVE SAMPLING (suspicious nodes) STAGING (not completely uniform)STAGING (not completely uniform) –Grade 2,3 endometrioid –Stage IC (with >50% myometrial invasion) –High risk histologic subtype without obvious extra-uterine disease

KEY MESSAGE! What is the risk this woman has (undetected) metastatic disease? a)<1% b)10% c)30% d)50% e)80%

“Every woman with (endometrial) cancer deserves individualized management that maximizes her prognosis and minimizes her morbidity.” “Documentation of disease extent via surgical staging allows optimal tailoring of adjuvant therapy to an individual patient’s risks.”