CA ENDOMETRIUM.pptx

CA ENDOMETRIUM.pptx

1. Management of Carcinoma Endometrium Dr Kiran

2. EPIDEMIOLOGY AND RISK FACTORS Endometrial cancer is the most common gynecologic cancer and the fourth most frequently diagnosed cancer in women in the developed countries. Probability of 1 in every 35 women (2.8%) developing it during her lifetime

3. Carcinoma of the Endometrium 3

4. Classification of Uterine Corpus Cancer

5. Endometrial Cancer: Type I AND II Type I Estrogen Related Younger and heavier patients Low grade Background of Hyperplasia Perimenopausal Exogenous estrogen Type II Aggressive High grade Unfavorable Histology Unrelated to estrogen stimulation Occurs in older & thinner women

6. CLINICAL PRESENTATION The most common presentation for endometrial cancer is postmenopausal vaginal bleeding ( 80% to 90%) Incidence of endometrial cancer in women presenting with postmenopausal bleeding range from 1% up to 25%, depending on patient age and the presence of other risk factors . Other patterns of presentations include vaginal discharge, abnormal Papanicolaou smear, or thickened endometrium on routine transvaginal ultrasound with advanced disease, they may present with urinary or rectal bleeding, constipation, pain, lower extremity lymphedema, abdominal distension due to ascites, and cough and/or hemoptysis.

7. DIAGNOSTIC WORKUP Endometrial tissue sampling remains the gold standard -achieved via biopsy or dilation and curettage (D&C) Endometrial biopsy- sensitivity in detecting endometrial cancer in postmenopausa l women is 99.6% compared to 91% in premenopausal women specificity is >98% for both groups D&C- , if symptoms persist, the office sampling is inadequate, or the patient is being considered for conservative fertility-sparing approaches Transvaginal ultrasonography (TVU)- Normal endometrium looks thin and homogeneously hyperechoic, but it is thickened and heterogeneous, with hyperplasia, polyps, and cancer

8. Thickness of 5 mm or greater as being abnormal. in premenopausal women, for whom the accuracy of TVU is limited because the endometrial thickness fluctuates, depending on the level of female hormones other methods are considered . Magnetic resonance imaging (MRI) - most accurate imaging study to assess tumor extension in endometrial cancer, especially myometrial invasion, tumor extension into the cervix . The reported sensitivity of MRI in detecting lymph node metastasis is on average 43.5% and the specificity is 95.9% . CEA-125

9. Staging –AJCC 7 th edition

10. Perez and Brady's Textbook of Radiation Oncology 7 th edition

11. SURGICAL MANAGEMENT Surgery is the primary treatment of both localized and advanced disease, the adequate surgical staging and pathological review. Total abdominal hysterectomy/BSO (TAH/BSO) is the most prevalent and time-tested form of simple hysterectomy in endometrial cancer. Minimally invasive surgery-laparoscopically or robotically.

12. Surgical Assessment of Lymph Nodes Lymphadenectomy - limit nodal assessment to inspection and removal of any enlarged/suspicious pelvic or paraaortic nodes. Lack of documented survival advantages to lymphadenectomy. full-pelvic and para-aortic lymph node sampling-surgical staging is the most accurate method to assess the extent of disease. Sentinel lymph node biopsy Medical Research Council [MRC]/A Study in the Treatment of Endometrial Cancer [ASTEC]

13. Risk Stratification ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma-2020

14. Low risk For patients with low-risk endometrial carcinoma, no adjuvant treatment is recommended (I, A). When molecular classification is known: For patients with endometrial carcinoma stage I–II, low-risk based on pathogenic POLE -mutation, omission of adjuvant treatment should be considered (III, A).

15. Role of RT in Stages I and II Observation Versus Pelvic RT Portec 1 -715 patients after TAH and BSO to observation VS pelvic RT Inclusion – IB-grade Ii and iii , ic -grade I and ii No lymph node sampling , pelvic rt dose was 46gy in 2gy 5yr vaginal / pelvic recurrence was 14% and 4% (p value <0.001) and os was 81%(rt) vs 85%(surgery) p value not significant Patient who relapsed locally after surgery were salvaged with subsequent rt

16. Pelvic RT Versus Intravaginal RT PORTEC-2 trial- 427 patients were randomized to pelvic RT (n = 214) or intravaginal RT (n = 213). Patients enrolled were those with stage IB grade 3 and >60 years old, IC grades 1 and 2 and >60 years old, and IIA grades 1 and 2 of all ages but with < 50% myometrial invasion. The dose of pelvic RT was 46 Gy given in 23 fractions. Intravaginal RT was delivered using a cylinder to treat the upper half of the vagina. With a median follow-up of 36 months, the 3-year vaginal recurrence rates were 0.9% in the intravaginal RT arm and 1.9% in the pelvic RT arm (P = .97).

17. PORTEC 2 VBT is very effective in ensuring local control keeping to a minimum risk of vaginal recurrence. Grades 1 and 2 acute GI toxicity was 53% versus 12% in favor of intravaginal RT (P < .001). This trial showed that intravaginal RT alone is sufficient to control vaginal recurrence even in patients with intermediate-risk features.

18. Intermediate Risk Adjuvant brachytherapy can be recommended to decrease vaginal recurrence (I, A). Omission of adjuvant brachytherapy can be considered (III, C), especially for patients aged <60 years (II, A). When molecular classification is known, POLE mut and p53abn with myometrial invasion have specific recommendations (see respective recommendations for low- and high-risk). For p53abn carcinomas restricted to a polyp or without myometrial invasion, adjuvant therapy is generally not recommended (III, C).

19. High Intermediate Risk Adjuvant brachytherapy can be recommended to decrease vaginal recurrence. EBRT can be considered for substantial LVSI and for stage II (I, B). Adjuvant chemotherapy can be considered, especially for high-grade and/or substantial LVSI (II, C). Omission of any adjuvant treatment is an option (IV, C). When molecular classification is known, POLE mut and p53abn have specific recommendations.

20. GOG-249

21. ASTRO 2017: GOG-249 Confirms Adjuvant Pelvic Radiation as Standard of Care for High-Risk, Early-Stage Endometrial Cancer.

22. High Risk EBRT with concurrent and adjuvant chemotherapy (I, A) or alternatively sequential chemotherapy and radiotherapy is recommended (I, B). Chemotherapy alone is an alternative option (I, B). Carcinosarcomas should be treated as high-risk carcinomas (not as sarcomas) (IV, B). When the molecular classification is known, p53abn carcinomas without myometrial invasion and POLE mu t have specific recommendations (see respective recommendations for lowand intermediate-risk)(III, C)

23. Phase III, international, open- label,multicentre , randomised trial at 103 centers 686 patients of high risk endometrial cancer enrolled Nov 2006 to Dec 2013 Randomised to CHEMORADIOTHERPY vs RADIOTHERPAY alone (1:1) Medain follow-up 60.2 months

24. Given in both treatment group Total dose 48.6 Gy 1.8 Gy fractions , 5 days a week In case of cervical involvement (glandular, stromal, or both), a brachytherapy boost was given to the vaginal vault. Brachytherapy dose was equivalent to 14 Gy in 2 Gy fractions (with recommended scheme of 10 Gy high-dose rate [HDR] in fractions of 5 Gy), specified at 5 mm from the vaginal vault surface. Two cycles of intravenous cisplatin 50 mg/m2 in the first and fourth we ek of external beam pelvic radiotherapy, followed by four cycles of intravenous carboplatin AUC5 and paclitaxel 175 mg/m2 at 21-day intervals TREATMENT

25. Results- PORTEC 3 Overall survival Failure Free Survival

26. Conclusion PORTEC 3 Treatment with chemoradiotherapy significantly improved 5-year failure-free survival for patients with high-risk endometrial cancer compared with radiotherapy alone but there was no significant difference in overall survival. women with stage III endometrial cancer, a significant improvement in failure free survival was found.

27. Advanced Disease In stage III and IV endometrial carcinoma (including carcinosarcoma), surgical tumor debulking including enlarged lymph nodes should be considered when complete macroscopic resection is feasible with an acceptable morbidity and quality of life profile, following full pre-operative staging and discussion by a multi-disciplinary team (IV, B). Primary systemic therapy should be used if upfront surgery is not feasible or acceptable (IV, A). In cases of a good response to systemic therapy, delayed surgery can be considered (IV, C). Only enlarged lymph nodes should be resected. Systematic lymphadenectomy is not recommended (IV, B)

28. Unresectable disease For unresectable tumours, multi-disciplinary team discussion should consider definitive radiotherapy with EBRT and intrauterine brachytherapy, or neoadjuvant chemotherapy prior to surgical resection or definitive radiotherapy, depending on response (IV, C). Image-guided brachytherapy is recommended to boost intrauterine, parametrial, or vaginal disease (IV, A). Chemotherapy should be considered after definitive radiotherapy (IV, B).

29. Recurrence Patients with recurrent disease (including peritoneal and lymph node relapse) should be considered for surgery only if it is anticipated that complete removal of macroscopic disease can be achieved with acceptable morbidity. Systemic and/or radiation therapy should be considered post-operatively Depending on the extent and pattern of relapse and the amount of residual disease (IV, C). In selected cases, palliative surgery can be performed to alleviate symptoms ( eg , bleeding, fistula, bowel obstruction) (IV, B). For locoregional recurrence, the preferred primary therapy should be EBRT.

30. Intracavitary brachytherapy Vault brachytherapy can be delivered using either a vaginal cylindrical applicator or vaginal ovoids Both are available in varying diameters/sizes Ovoids will treat the upper third of the vagina in most patients whereas cylindrical applicators can be loaded to treat any length of vagina required. According to the ABS, for endometrioid carcinoma of the endometrium, the proximal 3–5 cm of the vagina (approximately one-half) should be treated stage IIIB, the target is the entire vaginal canal. Prescribe to 0.5 cm beyond the vaginal mucosa

31. Doses Adj intracavitary RT alone- LDR is 50–60 Gy over 72 hrs (0.7–0.8 Gy/ hr ). The HDR is 21 Gy (7 Gy × 3) at 0.5 cm depth adj intracavitary RT given with WP RT- LDR doses of 30–40 Gy and HDR doses of 10–15 Gy (5 Gy × 2 or 3) at 0.5 cm depth are commonly used adjuvant rt-External beam irradiation- 45–50.4 Gy in 25–28 daily fractions of 1.8 Gy given in 5–51 ⁄2 weeks Unoperated stage I and II disease-EBRT 45 Gy in 25 daily fractions of 1.8 Gy given in 5 weeks followed by intracavitary irradiation Inoperable stage III disease-EBRT 50.4 Gy in 28 daily fractions of 1.8 Gy given in 51 ⁄2 weeks followed by intracavitary irradiation

32. OAR Constraints

33. Toxicities/complications Radiation: Acute toxicities- diarrhea , proctitis, abdominal cramps, fatigue, bladder irritation, drop in blood counts Late toxicities-vaginal dryness and atrophy, pubic hair loss, vaginal stenosis and fibrosis (recommend vaginal dilators), urethral stricture, fistula formation, SBO, chronic urinary and bowel frequency Surgical complications : leg edema (5% to 10%), lymphocysts (symptomatic in 5% to 7%), increased rates of deep vein thrombosis (2%) and small bowel obstruction (up to 5%), and increased blood loss and higher transfusion rates (5% to 10%)

34. Survival The 5-year survival rate is 80% to 90% for patients with stage I endometrial carcinoma. 60% to 80% for stage II. 30% to 80% for stage III disease because of the diverse extent of and prognosis for tumors classified as stage III.

35. Summary TAH+BSO is the standard surgery.

36. Thank u