gynecologic oncology update - university of utah

Gynecologic Oncology update

Park City Utah Postgraduate Course in the Department of Obstetrics and

Gynecology University of Utah/Huntsman Cancer

Institute

Andrew P. Soisson, MDDivision of Gynecologic Oncology

Endometrial Cancer/Incidence:

ACS estimates an incidence of approximately 60,000 cases of endometrial cancer in 2016.

The increased incidence appears to be occurring primarily in postmenopausal women. Since 2002, increased incidence of 2.5% for women age 50‐74 compared to 1.1% for women age 20‐49.

Sheikh and associates estimate that by 2030 there will be a 55% increase in cases of endometrial cancer.

SEER data suggests that approximately 15‐20% of women with endometrial cancer will be less than age 50 at the time of diagnosis. 2% will be less than age 40.


Introduction:

Most investigations show that women less than 40 with EMC are obese and nulliparous.

Most investigations show that young women with EMC have a better prognosis.

Several authors note that young women with EMC have a greater tendency for synchronous ovarian tumors.

Does not appear to be an increased incidence of Lynch Syndrome in young women with EMC.

Some authors suggest that young women with EMC who are not obese have a poor prognosis.


Young women with EMC, are they unique:

Women less than age 40.Grade 1 or II malignancies/endometriod type.

No evidence of myometrialinvasion, ovarian metastases, retroperitoneal adenopathy.

Compliant and likely to undergo follow‐up.

Endometrial Cancer/Fertility sparing treatment:

Criteria for treatment with progesterone:

Oral continuous medoxyprogesteroneacetate (Provera) 60‐180mg.

Oral continuous megesterol (Megace) 40‐480mg.

Progesterone containing IUD. Letrozole.GnRH agonists.Metformin. Tamoxifen.


Conservative treatment types.

Author # PTS Response Recurrence Pregnancy

Chen EIN = 16EMC = 37

EIN = 75%EMC = 73%

EIN = 19%EMC = 22%

EIN = 40%EMC = 14%

Baek EIN = 18EMC = 13

EIN = 89%EMC = 54%

EIN = 10%EMC = 31%

Falcone EMC= 28 90% 8% EMC = 87%

Laurelli EMC = 21 86% 10% EMC = 83%

Pronin EIN = 38EMC = 32

EIN = 92%EMC = 72%

EIN = 2%EMC = 6%

Simpson EIN = 19EMC = 25

55%

Shan EIN/EMC = 26 81%

Gonthier EIN/EMC = 40 Obese=67%Non‐

obese=75%

Obese=20%Non‐obese=12%

Obese=13%Non‐

obese=48%

Gong EIN = 21EMC = 9

EIN = 86%EMC = 56%

EIN = 57%EMC = 50%

EIN = 48%EMC = 44%

Ohyagi EIN = 11EMC = 16

EIN + 82%EMC = 69%

EMC = 82%

N = 10 EIN = 75‐92%EMC = 54‐90%

EIN = 2‐57%EMC = 6‐82%

EIN = 48‐87%EMC = 14‐87%

Progestin therapy outcomes:

55 women less than age 40 with EIN or EMC at IHC and the University of Utah/HCH

Number (%)Megace 35 64%Provera 13 24%Mirena 6 11%Norethindrone 1 2%




Number (%)Cancer 17 31%Hyperplasia 38 69%G0 29 53%Hispanic 12 22%Asian 2 4%Pacific Islander 7 13%Middle Eastern 1 2%Caucasian 33 60%BMI 40Referral to REI 23 36%



Number (%)Response 31 56%Non‐response 24 44%Recurrence/persistence

20 36%

Pregnancy 11 20%REI +pregnancy

22%

No REI + pregnancy

19%


18 women with EMC who elect to undergo fertility sparing treatment.

72% are nulligravid. Response rate = 27% 83% develop recurrence or persistence of disease, 72% ultimately have hysterectomy.

No patients achieve pregnancy, 50% consult REI.No difference in BMI responders versus non‐responders.

Progestin therapy outcomes/University of Utah/IHC:


Letrozole shown to have anti‐proliferation effects on endometrial cancer cell lines.

16 women treated with preoperative anastrozole prior to hysterectomy: decreased cellular proliferation, decreased expression of ER and AR.

Case report of 2 women with EMC treated with provera and anastrozole.

We have treated 4 women with progesterone and anastrozole.


Conservative treatment types/anastrozole.

Type of progesterone has not been well studied, most studies utilize medoxyprogesterone acetate (Provera) or megesterol (Megace) with a wide range of doses.

Dose varies in multiple studies: GOG studied 200 mg versus 1,000 mg of Provera with no difference in response: in breast cancer recurrence 800mg of Megace better than 160mg.

Route of administration: Randomized trial in EIN showed 100% response with IUD compared to 96% for continuous oral progesterone and 69% for cyclic oral progesterone.

Side effects: Cholakian demonstrated less weight gain and systemic side effects with IUD versus oral progesterone.



Candidates for fertility sparing treatment should be less than 40 with a grade I or II endometriod cancer.

MRI with no MI, ovarian metastases, or retroperitoneal adenopathy.

Pretreatment hysteroscopy with resection of visible tumor and D&C.

Treatment with progestin IUD for 6‐12 months. Consider anastrozole if morbidly obese. Follow‐up hysteroscopy and D&C to asses response. Close follow‐up as recurrence rates are high.


Recommended treatment of EIN/EMC.

Estrogen sensitive tumor and preservation of the ovaries will compromise cure and increase the risk of recurrence of tumor.

Risk of synchronous ovarian cancer. Risk of metastases to the ovary. Increased risk of subsequent epithelial ovarian cancer.

3‐5% of women with endometrial cancer have the Lynch Syndrome.

Endometrial Cancer/Ovarian preservation:

Rationale for oophorectomy during hysterectomy:

Author # Patients Survival outcomeLau 17 NDLee 175 NDLi 20 NDSun 20 NDWright 402 NDWright 1121 NDMatsuo 4109 NDGu 1419 NDKoska 184 ND

N = 9 7467 ND

Endometrial Cancer/Ovarian preservation:

Ovarian preservation: survival

Author # PTS Incidence synchronous tumors

Incidence metastatic tumors

Walsh 102 23% 3%Lee 260 3% 5%Pan 976 .3% 2%

Navarria 1365 2%Kinjyo 48 5%

.3 ‐ 23% 2 – 5%

Endometrial Cancer/Ovarian preservation

Ovarian preservation: Incidence of synchronous and metastatic tumors.

Incidence in the general population 1‐500 to 1‐1000 Approximately 2‐3% of CRC associated with HNPCC syndrome, 3‐10% for women less than 50.

Approximately 3‐5% of EMC associated with HNPCC. 3 relatives with CRC or Lynch syndrome associated cancer.

Endometrial hyperplasia in women less than 50 years of age should not be an indication for HNPCC screening.

Physicians do a poor job screening patients for potential risk of HNPCC.

Endometrial Cancer/Lynch Syndrome screening.

Universal screening for Lynch:

Median age = 48 years of age. 40‐60% life time risk of EMC, 20% less than age 50. 5‐15% risk of OVCA/median age = 45, similar histology. 80% have endometriod histology, MMT and papillary serous tumors reported.

OVCA: presents at early age, early stage, and non‐serous histology.

Risk of EMC is 26% within 10 years of diagnosis of CRC.

Over half have no family history. Risk increased if less than 50 and obese.



Three or more relatives with histologically verified Lynch syndrome‐associated cancers (CRC, cancer of the endometrium or small bowel, transitional cell carcinoma of the ureter or renal pelvis), one of whom is a first‐degree relative of the other two and in whom familial adenomatous polyposis (FAP) has been excluded.

Lynch syndrome‐associated cancers involving at least two generations.

One or more cancers were diagnosed before the age of 50 years.



MMR genes associated with mismatch repair system

Gene name Frequency ChromosomeMLH1 40-45% 3p21.3MSH2 40-45% 2p22-p21MSH6 7-10% 2p16PMS1 unknown 2q31-q33PMS2 <5% 7p22MSH3 0% 5q11-q12MLH3 0% 14q24.3



Life time risk for femalesCA site MLH1 MSH2 MSH6 PMS2Any 50‐76% 38‐78% 65% 21‐53%CR 50‐53% 39‐68% 18‐30% 15%EMC 60% 21% 30% 15%OV 20% 24% 1%GU .4% 9% 1%


Universal screening for Lynch: Riskof malignancy

Analysis of 272 women with EMC/universal Lynch testing University of Utah/HCH

Parameter #Abnormal IHC staining 87 (32%)MLH1/PSM2 67Methylation + 63Methylation ‐ 4MSH6 + 5MSH2/MSH6 + 11PSM2 +MSH2 + 2Candidates for sequencing 2DNA sequencing 24DNA sequencing + 22

Total number with Lynch 9 (3%)



Parameter # tested CostIHC staining 272 $54,440

DNA methylation

67 $19,765

Counseling 24 $1,364Letters 287 $6,314

Phone calls 42 $462DNA sequencing 22 $65.660

Total $148,005Cost/patient $16,445

Cost associated with universal Screening for the Lynch Syndrome.

gynecologic oncology update - university of utah

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