Carcinoma endometriale: la terapia adiuvante Quale e Quando

Presentazione sul tema: "Carcinoma endometriale: la terapia adiuvante Quale e Quando"— Transcript della presentazione:

1 Carcinoma endometriale: la terapia adiuvante Quale e Quando
Vincenzo Scotto di Palumbo Ospedale Santo Spirito in Sassia Roma

2 La stadiazione FIGO 1988

3 Grading e sopravvivenza

4 Invasione miometriale e sopravvivenza

5 Il problema linfonodale

6 Fattori di prognosi e sopravvivenza

7 Terapia adiuvante ormonoterapia radioterapia chemioterapia
combinazioni

8 Ormonoterapia Cochrane Gynecological Cancer Group:
“Progestagens for endometrial cancer” Metanalysis of 6 clinical trials (4351 patients) Only 3 trials with Stage I patients In 3 trials also patients with advanced disease Martin-Hirsch P L, Jarvis G, Kitchener H, Lilford R. Progestagens for endometrial cancer (Cochrane Review). The Cochrane Library, Issue 1, 2008

9 Cochrane review: adjuvant progestagens

10 Radioterapia adjuvante
Fasci esterni Brachiterapia Combinazione delle due modalità

11 Locoregional recurrence All stage I patients: External beam radiotherapy vs No external beam radiotherapy Distant recurrence All stage I patients: External beam radiotherapy vs No external beam radiotherapy Adjuvant radiotherapy for stage I endometrial cancer; systematic review and meta-analysis (Cochrane Review). In: Annals of Oncology 22, , 2007

12 Endometrial cancer related deaths
Subgroup analysis of patients at least 1 high risk factor, Ic or grade 3 Endometrial cancer related deaths Subgroup analysis of patients at least 2 high risk factor, Ic or grade 3 Adjuvant radiotherapy for stage I endometrial cancer; systematic review and meta-analysis (Cochrane Review). In: Annals of Oncology 22, , 2007

13 Adjuvant external beam radiotherapy (EBRT) in the treatment of endometrial cancer: results of the randomized MRC ASTEC and NCIC CTC EN.5 trials Inclusion criteria Stage 1A grade 3 Stage 1B grade 3 Stage 1C grade 1-3 Serous or clear-cell cancers EN.5 started July 1996; ASTEC July 1998 905 patients randomized J Orton. ASCO 2007

14 Results Overall Survival Recurrence-free Survival
Isolated Vaginal or Pelvic Initial Recurrence J Orton. ASCO 2007

15 Metanalisi su overall survival
0.2 % difference in 5-year OS (87.8% in EBRT and 88% in no EBRT) 95% CI of difference = -2.0% to 3.0% J Orton. ASCO 2007

16 Maggi R, BJC 95: , 2006

17 Caratteristiche dello studio
Inclusions criteria Stage IC grade 3 Stage IIA-IIB grade 3 with myometrial invasion > 50% Stage III Maggi R, BJC 95: , 2006

18 Sopravvivenza libera da malattia
Maggi R, BJC 95: , 2006

19 Sopravvivenza totale Maggi R, BJC 95: , 2006

20 Stage III or IV “low volume” - Any histology Residual tumour less than  2 cm after surgery 424 pts
Whole abdominal radiotherapy (WAI) 30 Gy in 20 daily fractions Boost to the pelvis or to an extended field encompassing pelvic and para-aortic lymph nodes Chemotherapy Doxorubicin 60 mg/m2 Cisplatin 50 mg/m2 Every 3 weeks, for 8 cycles (only Cisplatin was to be infused during the 8°cycle) Randall ME, J Clin Oncol 24: 36-44, 2006

21 Sopravvivenza libera da malattia
HR 0.71 (95%CI , p<0.01) Randall ME, J Clin Oncol 24: 36-44, 2006

22 Sopravvivenza totale 55% 42% HR 0.68 (95%0.52-0.89, p<0.01)
Randall ME, J Clin Oncol 24: 36-44, 2006

23 Conclusions Randall ME, J Clin Oncol 24: 36-44, 2006

24 NSGO EORTC A randomized phase III study on adjuvant treatment with radiation (RT) +/- chemotherapy (CT) in early stage high-risk endometrial cancer (NSGO-EC-9501/EORTC 55991) Inclusion criteria Stage IC, II or III cancer plus grade 3 histology Serous or clear-cell cancers Aneuploid tumors plus grade 3 histology Aneuploid tumors plus stage IC, II or III cancer Thomas Hogberg, ASCO. 2007

25 NSGO EORTC A randomized phase III study on adjuvant treatment with radiation (RT) +/- chemotherapy (CT) in early stage high-risk endometrial cancer (NSGO-EC-9501/EORTC 55991) RANDOMIZATION Thomas Hogberg, ASCO. 2007

26 Sopravivenza libera da malattia
HR 0.62 (CI ) p=0.03; estimated difference in 5-yr PFS 7% from 72% to 79%

27 Sopravivenza totale HR 0.65 (CI 0.40-1.06) p=0.08;
estimated difference in 5-yr OS 8% from 74% to 82%

28 Considerazioni degli autori
HR 0.35 (CI ) p=0.009; estimated difference in 5-yr PFS 14% from 73% to 87%

29 Conclusions Despite that 27% of patients randomized to CT+RT received no, or only party of the prescribed CT, CT+RT was better than RT alone as adjuvant therapy for patients with early endometrial cancer at high risk for micrometastases

30 GOG 184 Register R Endometrial carcinoma A N Surgical stage III D
Regimen I* Doxorubicin** 45mg/mq Cisplatin 50mg/mq G-CSF*** 5mcg/kg 2-11 R A N D O M I Z E Endometrial carcinoma Surgical stage III Hysterectomy and BSO <2 cm Residual disease Optimal Lymph Node Sampling Pelvic +/- Para-Aortic Irradiation Intravaginal Brachytherapy Regimen II* Doxorubicin** 45mg/mq day 1 Cisplatin 50mg/mq day 1 Paclitaxel 160mg/mq day 2 G-CSF*** 5mcg/kg 3-12 *q weeks 3 x 6 courses **Maximum total doxorubicin dose is 270 mg/mq for both regimen

31 Serie OSS 2005 - 2007 Laparotomia Laparoscopia Età media 75 64
BMI medio 23.7 19.3 Stadio: Ia 6 1 Ib 7 3 Ic IIa IIb 2 IIIa 4 IIIc IVb Istotipo: Adenocarcinomi 29 Sieropapilliferi Adenosquamosi N. medio di linfonodi 20.1 13.4 Tempo operatorio medio (min) 102 205 Perdita ematica media (cc) 105 82

32 OSS policy st I Ia G1, G2 osservazione Ia G3 RT pelvica se presenti RF
Ib G1, G2 osservazione Ib G3 RT pelvica se presenti RF Ic G1 osservazione Ic G2, G3 RT pelvica + CT istotipi speciali RF età>60a, LVI, dimensioni del T, coinvolgimento della parte bassa del corpo

33 OSS policy st II, III IIa G1 osservazione IIb G2, G3 RT pelvica
IIIa G1, G2 osservazione se solo cit + IIIa G3 RT pelvica + CT IIIb CT + RT IIIc CT + RT pelvi ev LA

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