Endometrial Cancer care by the gynecologist

James BentleyProfessor

Department of Obstetrics and Gynecology Dalhousie University

Halifax NS

Disclosure of Potential for Conflict of Interest

Facilitator’s Name: Dr James Bentley

Grants/research support: Merck, GSK, Guided Therapeutics, Amgen

Speaker’s bureau/honoraria: Merck, GSK

Consulting fees: GSK

Mitigation of Potential for Conflict of Interest

• Although I have been involved with HPV vaccine companies and a new screening modality, I will not be discussing this in my presentation today.

Epidemiology

• Commonest malignancy of the female genital tract– About 5600 cases per year and 1000 deaths per year in Canada– 4th commonest malignancy in Canadian women after breast, lung, colorectal– 9th as cause of death in women– < 25% occur before menopause, peak at 58-60– 5 % in women less than 40– 2.6 % rise in incidence per year

Canadian Cancer Statistics 2014

Endometrial Cancer; Risk factors

Increased RiskObesity 21-50 lbs 3X

Obesity > 50lbs 10X

Nulliparous 2X

Menopausal > 52 yrs 2.4X

Diabetes 2.5X

PCOS

E2 secreting tumor

Unopposed E2 4-7X

Tamoxifen 4X

HNPCC 40-60X

Decreased RiskOvulation

Hormonal Contraception (E2) 0.46X

progestin

Menopause <49

Normal weight

multiparity

smoking

Pathology

• Endometroid ( good prognosis)– Classical risk factors– presents early– good survival

• Others:Uterine serous, clear cell, undifferentiated ( poor prognosis)– classic associations not present– present with advanced disease – poor survival

What is endometrial cancer?Endometriod

Grade 1

Grade 2

Grade 3

Uterine papillary serous

Clear Cell

FIGO Staging 2009Stage I Tumor confined to the corpus uteri

IA No or less than 50% myometrial invasion

IB Invasion equal to or greater than 50% of the myometrium

Stage II Tumor invades cervical stroma, but does not extend beyond uterus*

Stage III Local and/or regional spread of the tumor

IIIA Tumor invades the serosa of the corpus and/or adnexae

IIIB Vaginal and/or parametrial involvement

IIIC Metastases to pelvic and/or para-aortic lymph nodes

IIIC1 Positive pelvic nodes

IIIC2 Positive para-aortic nodes +/- positive pelvic nodes

Stage IV Tumor invades bladder and/or bowel mucosa and or distant mets

IVA Tumor invades bladder and/or bowel mucosa

IVB Distant mets, including intra abdominal and/or inguinal lymph nodes

* Endocervical glandular involvement only is considered as Stage I

Post menopausal bleeding: evaluation• Recommendations?• Pap test (if not done recently)• Endometrial Biopsy

• What if can’t do office Bx?• US +/- hysteroscopy D&C

Challenges: preoperative biopsy

• How accurate is the biopsy?– Can underestimate the stage in up to 20%– Challenges of AEH, up to 40% will have

endometrial cancer on final biopsy– Should be able to identify Grade 3 and pap

serous/ clear cell carcinomas

Management post diagnosis

• Consider pathology review• Grade 1:

– Pre-op assesment• CXR

– Hysterectomy BSO• Grade 2, 3, Uterine Papillary Serous Carcinoma, Clear

Cell• Unfit for Surgery• Obvious metastatic/ unresectable disease

– REFER TO Gynecologic Oncologist for management

Not a generalist case!

Why stage?

• Extent of disease• Determine adjuvant disease• Prognostication• Compare results• ? Therapeutic benefit

Grade 1: myometrial evaluation

• MRI can evaluate depth of invasion and hence identify women who may benefit from lymphadenectomy

• Grade 1 with deep myoinvasion, lymph node involvement ~10%

• Can be assessed at time of OR either by gross inspection or frozen section

Surgical approach

• Just because FIGO describes Hyst BSO and nodes does not mean that all cases need “full staging”

• Role of laparoscopy• Nodes for who• Overall nodal risk for Grade 1 disease is ~ 3%

for pelvic and 2 % for paraortic nodes• No evidence that lymphadenectomy in proves

outcome

Kwon et al.2009

• Ontario data• 316 women with lymphadenectomy 1996-2000• Mean age 62.2• 12% +ve nodes• 23% adjuvant Rx• Risk of death increased with:

– Invasion >50%– Cervical stromal invasion– Age >60 yrs– Grade 3

Kwon et al

Role of Adjuvant Rx

GOG 99TAH BSO most had nodesall stage 1B 1C 2A 2Brandomized to WPXRT vs observation reassessed LIR and HIRrisk factors: increasing age, grade 2-3, LVI, outer third MIreduced local recurrence 9% to 0.5%; distant 6.4% to 5.3%overall slight survival advantage to RT (86% to 92%) but not stat. significantLIR survival similar in both arms, but in HIR somewhat lower overall death rate

Portec 1TAH BSO (no nodes done) grade 1 stage 1C, grade 2 1B 1C, grade 3 stage 1Brandomized to WPXRT or observationlocoregional recurrence-4% vs 14%(73% vagina--70 % salvaged)distant mets 8% vs 7%overall survival no diffgrade 1+2 >50%, grade 3= 10% risk of locoregionalrecurrencegrade 3-- 14% risk of distant mets, and 16% risk of deathlocoregional relapse 3 fold higher if age was over 60CRITICISM low risk disease over-represented (30% 1B gr2)

What is High risk disease?

• Grade 3• Stage 1B (2009)• Stage 2

ASTEC/EN5

intermediate and high risk ECrandomized to EBRT vs observationabout half of the observation pts got brachyno survival advantage of EBRTlocoregional recurrence 7% vs 3.6%

lower than PORTEC likely b/c of brachy

PORTEC-2 march 2010

• 427 pts stage 1 or IIA endometriod ca• Routine Lymphadenectomy not done• Eligible if:

– >60 yrs old– Stage 1C grade 1 or 2, 1B grade 3, stage 2A any age

• Randomised to brachy vs. WPT• 3 rec’s vs 4• No benefit of WPT

Who needs radiation?

• No improved survival• Better pelvic control• Less vaginal recurrences• BUT….• Vaginal recurrences usually salvaged

• ? In combination with chemo Rx

• Stage 2 (beware grade 3!)

Role of chemotherapy

• GOG 122• Stage III and IV with minimal extrauterine

disease• WART vs AP• AP had improved survival• Recurrences in pelvis and abdomen

Which Chemo Regieme

• No great evidence yet for carbo taxol• BUT..• Hogberg

– European trial in abstract form:– 382 patients with stage I, II, IIIA or IIIC and adverse

features • Deep MI, clear cell, serous, anaplastic, nondiploid

– Chemo one of :AP, TAP, TP vs. XRT– Improved PFI at 5 yrs with chemo rx (7%)– No difference between chemo arms

Practical approach: SurgeryGrade 1, clinical stage 1 Hysterectomy BSO and 1 set

of washingsGrade 2, 3 clinical stage 1 Hysterectomy BSO PLND,

consider PA nodesStage 2 clinically Consider Radical

HysterectomyClinically advanced disease Individualise, but TAHBSO

and debulkClear cell, serous Hysterectomy BSO, PLND,

PAND and staging

Practical approach: Adjuvant Rx

Stage 1 No high risk features NFTStage 1 High risk features* Study, Brachy; chemo and

brachy for 1C gr 3Stage 2 WPRStage 3 c Study, combined therapyClear cell, serous Study, chemo XrtStage 4B chemotherapy

Adverse features: grade 3, deep MI, cervical stromal involvement, age > 60

Follow- Up

• No distinct benefit of follow-up in low risk disease• BUT provides psychological benefit• Commonest sites of recurrence vagina, pelvis and chest• No role for Pap smear, CT scans• Hx and Exam

– q 3 months for first year– q 4 months second year– q 6 months third year +/- CXR– Annually to 5 years

Conclusion

• Endometrial Cancer is common and will be increasing in your practice

• Carefully evaluate the patient• Work closely with the gynecologic oncologists

in your center re referral practices etc

SOGC/GOC Guidelines April 2013

Epidemiology and Investigation for Suspected Endometrial CancerThe Role of Adjuvant Therapy in Endometrial CancerThe Role of Surgery in Endometrial Cancer

http://sogc.org/clinical-practice-guidelines/