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ADJUANT TREATMENT IN CA ENDOMETRIUM

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ADJUANT TREATMENT IN CA ENDOMETRIUM

  1. 1. ADJUANT TREATMENT IN ENOMETRIAL CANCER Dr Paul George
  2. 2. • Based on retrospective histopathological analyses and prospective adjuvant studies three risk groups were characterized: low, intermediate, and high risk
  3. 3. Overall the 5-year survival rates for all grades and histologic subtypes are approximately • 78%-90% for stage I, • 74% for stage II, • 36%-57% for stage III, and • 20% stage IV
  4. 4. LOW RISK • Stage IA, Grade 1-2 Stage IB, Grade 1 • Well or MD • Meta analysis of 8 studies • 2nd malignancy (hazard ratio [HR], 2.02 • higher risk of mortality (HR, 1.36)and • had experienced lower quality of life from significant radiation toxicity
  5. 5. • Therefore, patients in the low risk category do not generally receive adjuvant treatment, but are followed-up carefully during the surveillance period
  6. 6. INTERMEDIATE RISK
  7. 7. RESULTS Adj RT Stage I, II PORTEC GOG-99 RISK FACTORS AGE >60 G - 3 MYO INV >50% <50/ <60/<70 2-3 >66% LVI + HIGH intermediate RISK 2 OUT OF 3 ANY AGE + 3 FACTORS >50 + 2 FACTORS >70 + 1 FACTOR RESULTS 10 Yr LRR RT- 5 % NO Rx- 23% 4 yr result RT- LRR- 5%, 13% ANY SITE NO Rx- LRR- 13%, 27 % ANY
  8. 8. INTERMEDIATE RISK • Based on GOG 99 & PORTEC • LOW IR Stage IA, grade 3 Stage IB, grade 2 Stage IIA, grade 1-2, <50% MI • HIR Stage IB, grade 3 Stage IC, grade 1-2 Stage IIA, grade 3, <50% MI Stage IIA, grade 1-2, >50% MI +/-+LVSI G2-3,LVI, >66%MI 1/3 above w/ age >70 2/3 above w/ age <50 3/3 above w/age <50
  9. 9. Adjuant Pelvic RT in Early EC ALDERS ET AL 1980 PORTEC1 GOG99 ASTEC/EN5
  10. 10. • Adjuant pelvic RT improves local control but failed to show a survival advantage • In all studies, adjuvant PRT was associated with significant radiation-related toxicities including diarrhea, fecal leakage, urinary frequency and urgency, which negatively affected quality of life.2nd malignancies
  11. 11. To circumvent adverse effects related to radiotherapy, while not compromising outcomes, a subsequent trial, PORTEC-2 compared vaginal brachytherapy (VBT) to PRT
  12. 12. • the VBT group suffered significantly lesser toxicities compared to the PRT group. • The rate of acute grade 1-2 gastrointestinal (GI) toxicity was significantly lower in the VBT vs. PRT group (12.6% vs. 53.8%). • These results support using VBT for patients with patients with HIR early stage EC.
  13. 13. Role of chemo • JGOG 2033 PRT vs Cisplatin based chemo • EORTC 55991 • Maggi et al • All studies showed that the use of chemotherapy lowered the risk of distant metastasis, but did not improve OS in the overall study population • Protocols JGOG 2033 and EORTC 55991 demonstrated an improvement in OS with the use of chemotherapy in the higher risk subgroup defined as either stage II-IIIA or stage IC, grade 3 and/or age >70 (73.6% vs. 89.7%, p=0.006 in JGOG 2033; 75% vs. 82%, p=0.046 in EORTC 55991
  14. 14. • To definitively address whether chemotherapy improves survival in early stage uterine cancer, protocols PORTEC-3 and GOG 249 were designed
  15. 15. The highly anticipated results of these studies will definitively answer whether or not systemic chemotherapy has a place in the management of high risk early stage EC
  16. 16. HIGH RISK • Stage IC, grade 3 • Stage IIA, grade 3, >50% MI • Stage IIB, any grade • UPSC • CCC • Stage III-IV
  17. 17. TREATMENT FOR ADVANCED STAGE ENDOMETRIAL CANCER • WAI/CHEMO • 1983 Greer and Hamberger shows fiirst series of adjuant WAI improves OS • Other retrospective studies have shown that most of the disease relapses systemically • The results of these studies reiterated the concept that stage III &above EC should be considered a systemic disease, for which effective systemic therapy is required
  18. 18. Role of Multiagent chemo • GOG 107 & 163 showed improved response rate for AP regimen in metastatic & recurrent EC
  19. 19. GOG122 This trial set a new standard for patients with locally advanced EC, bringing systemic chemotherapy to the forefront of EC management However 18% of patients treated on the AP arm developed pelvic recurrence as the first site of relapse despite improved systemic control compared to WAI, local control remains insufficient
  20. 20. Triplet GOG 177 TAP vs AP Better RR , PFS & OS in metastatic setting
  21. 21. • GOG184 These results suggested that TAP although highly active in the metastatic setting, is not superior to the doublet regimen omitting paclitaxel and is too toxic to be administered routinely after tumor volume directed radiotherapy in the adjuvant setting.
  22. 22. • LESS TOXIC CT (Pacli +carbo) GOG209 Naakumura et al Several other studies confirm that CT is not inferior to TAP and as active as AP Better toxicity profile favours CT as the std chemotherapy regimen for Advanced EC
  23. 23. • AP, TAP , CT all are active in EC
  24. 24. Combined modality treament in locally advanced EC 30% of patients included in GOG-122 treated with systemic chemotherapy recurred in the pelvis and in the abdomen. This observation suggested that patients treated with systemic chemotherapy experience a finite rate of local failure, which could compromise in overall survival. This concern supported including tumor volume directed radiotherapy in the upfront approach of stage III/IVA EC, with the intent of preventing local recurrences. Whether this improved local control translates into an improvement in OS remains unproven
  25. 25. CHEMORADIATION Several small studies Onda et al Bruzzone et al Hogberg et al Combination chemoradiation is superior in terms of PFS & OS RTOG phase II ITALIAN study concurrent chemoRT
  26. 26. GOG 184 combined approach yielded a three-year DFS of 62%-64% in this setting
  27. 27. • The ongoing international protocol GOG 258 compares tumor volume-directed radiotherapy administered concurrently with cisplatin and followed by 4 cycles of CT against CT chemotherapy alone
  28. 28. • It is anticipated that GOG 258 will answer critical questions regarding the • impact of chemo-radiation on OS, • the tolerability of the approach, and • the short- and long-term impact on the quality of life. • If positive, the combined chemo-radiotherapy approach would become a new standard of care in locally advanced EC
  29. 29. Summarising
  30. 30. GENERAL PRINCIPLE OF MANAGEMENNT RISK STRATIFICATION Low risk Int. low risk Int. high risk High risk Stage IA, Grade 1-2 Stage IA, grade 3 Stage IB, Grade 1 Stage IB, grade 2 Stage IIA, grade 1-2, <50% MI Stage IB, grade 3 Stage IC, grade 1-2 Stage IIA, grade 3, <50% MI Stage IIA, grade 1-2, >50% MI +/-+LVSI G2-3,LVI, >66%MI 1/3 above w/ age >70 2/3 above w/ age <50 3/3 above w/age <50 Stage IC, grade 3 Stage IIA, grade 3, >50% MI Stage IIB, any grade UPSC CCC Stage III-IV
  31. 31. MANAGEMENT LOW RISK LOW INTERMEDIATE HIGH INTERMEDIATE HIGH OBSERVATION VBT if Age>60 LVI Lower uterine segment involvement OBSERVATION/VBT VBT ALONE PELVIC EBRT IF ESS NOT DONE STAGING LAPAROTOMY+ PELVIC EBRT+ VBT+ CHEMO
  32. 32. Hormone Replacement Theraapy controversial Reasonable option for Stage I
  33. 33. FOLLOW UP • Physical examination 3-6months for 2-3years • Annnually thereafter • CA 125 optional • Imaging as indicated • Genetic counselling • Patient education lifestyle, nutrition obesity, potential recurrence • Sexual health , vaginal dillators/lubricants
  34. 34. 66yr old lady who is evaluated for postmenopausal bleeding and diagnosed to have ca endometriumUnderwent staging lap with TAH+ BSO with lymph node sampling After complete HPE MD Endometroid adenoca stage IC G2 with no LVI
  35. 35. • RISK?????
  36. 36. GENERAL PRINCIPLE OF MANAGEMENNT RISK STRATIFICATION Low risk Int. low risk Int. high risk High risk Stage IA, Grade 1-2 Stage IA, grade 3 Stage IB, Grade 1 Stage IB, grade 2 Stage IIA, grade 1-2, <50% MI Stage IB, grade 3 Stage IC, grade 1-2 Stage IIA, grade 3, <50% MI Stage IIA, grade 1-2, >50% MI +/-+LVSI G2-3,LVI, >66%MI 1/3 above w/ age >70 2/3 above w/ age <50 3/3 above w/age <50 Stage IC, grade 3 Stage IIA, grade 3, >50% MI Stage IIB, any grade UPSC CCC Stage III-IV
  37. 37. Adjuant treatment???
  38. 38. To circumvent adverse effects related to radiotherapy, while not compromising outcomes, a subsequent trial, PORTEC-2 compared vaginal brachytherapy (VBT) to PRT
  39. 39. • chemo????
  40. 40. • To definitively address whether chemotherapy improves survival in early stage uterine cancer, PORTEC-3 and GOG 249 were designed
  41. 41. • Thank you…………….. dr paul george
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