Clinical session  Gynecological cancers  Cervical and endometrial cancers Prof. C. Sessa IOSI - Bellinzona 10° ESO-ESMO MA...
Cervical Cancer <ul><li>Third most common cause of female mortality </li></ul><ul><li>Incidence 13.2/100’000 women/yr Euro...
Cervical Cancer <ul><li>Bimanual P/V examination, colposcopy, biopsy and/or endocervical currettage </li></ul><ul><li>MRI ...
Cervical Cancer The FIGO staging Difficulties in clinical/radiological evaluation local extension (corpus, parametrium, pe...
Survival by FIGO stage Cervical Cancer
Survival by nodal status Cervical Cancer
Cervical Cancer Treatment *PLND: pelvic lymphadenectomy  **  ≥ 4 cm, ± pelvic node involvement ***  RT: EBRT +BRT ± LA EBR...
NIH Consensus Statement on Cervical Cancer  Bethesda 1996 “  patients with stage IB and IIA cervical cancer are appropriat...
2/22/99: NCI issues clinical announcement on cervical cancer <ul><li>The results of 5 large studies have shown that women ...
 
<ul><li>significant improvement (p<0.0001) of </li></ul><ul><ul><li>overall survival (> 6%) </li></ul></ul><ul><ul><li>ove...
<ul><li>“ strong consideration should be given to the incorporation of concurrent cisplatin based chemotherapy in women wh...
<ul><li>Fertility sparing surgery in early stages:  </li></ul><ul><li>radical trachelectomy + PLND (RT+PLND) in stages IA1...
CONCLUSIONS CT/RT is considered the world standard treatment for LACC Neoadjuvant CT followed by surgery may represent an ...
55994 EORTC Treatment scheme
Treatment <ul><li>Stage IVB </li></ul><ul><li>Recurrence  not suitable for local treatment (pelvic and extrapelvic) </li><...
Bevacizumab   in advanced cervical cancer <ul><li>Single agent in recurrent disease (GOG-227 C) </li></ul><ul><li>Four arm...
Phase II trial of Bevacizumab in persistent/recurrent squamous cell carcinoma  of the cervix - a GOG study <ul><li>46 pts,...
Bevacizumab in advanced cervical cancer <ul><li>Single agent in recurrent disease (GOG-227 C) </li></ul><ul><li>Four arm s...
<ul><li>In order to minimize morbidity, primary therapy should avoid the planned use of both radical surgery and radiation...
<ul><li>19 randomized studies of RCT (2 not published) </li></ul><ul><ul><li>12 platinum based (+/- BLM, VCR, 5FU) </li></...
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MCO 2011 - Slide 15 - C. Sessa - Cervical and endometrial cancers (part II)

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MCO 2011 - Slide 15 - C. Sessa - Cervical and endometrial cancers (part II)

  1. 1. Clinical session Gynecological cancers Cervical and endometrial cancers Prof. C. Sessa IOSI - Bellinzona 10° ESO-ESMO MASTERCLASS IN CLINICAL ONCOLOGY Ermatingen, 4.4.2011
  2. 2. Cervical Cancer <ul><li>Third most common cause of female mortality </li></ul><ul><li>Incidence 13.2/100’000 women/yr Europe </li></ul><ul><li>Mortality 5.9/100’000/yr </li></ul><ul><li>Incidence and mortality higher in developing countries </li></ul><ul><li>Aetiological factors High risk HPV persistent infection </li></ul><ul><li>Predisposing factors Early age first intercourse </li></ul><ul><li>Early pregnancies </li></ul><ul><li>Squamous 80% </li></ul><ul><li>Adenocarcinoma 10-20% </li></ul>Epidemiology
  3. 3. Cervical Cancer <ul><li>Bimanual P/V examination, colposcopy, biopsy and/or endocervical currettage </li></ul><ul><li>MRI pelvis/abdomen: local extension and nodal metastases </li></ul><ul><li>Thoracic CT </li></ul><ul><li>Prognostic factors: stage, tumor size, stromal invasion, nodal involvement, limphovascular space invasion (LVS), histotype </li></ul>Diagnosis and biology
  4. 4. Cervical Cancer The FIGO staging Difficulties in clinical/radiological evaluation local extension (corpus, parametrium, pelvic wall) nodal involvement
  5. 5. Survival by FIGO stage Cervical Cancer
  6. 6. Survival by nodal status Cervical Cancer
  7. 7. Cervical Cancer Treatment *PLND: pelvic lymphadenectomy ** ≥ 4 cm, ± pelvic node involvement *** RT: EBRT +BRT ± LA EBRT <ul><li>Combination CT/RT*** with cisplatin </li></ul><ul><ul><li>Level of evidence B1 </li></ul></ul>III/N IIA**/B <ul><li>Combination CT/RT with Cisplatin is the standard </li></ul><ul><li>Poor risk** </li></ul><ul><ul><ul><ul><ul><li>Level of evidence A </li></ul></ul></ul></ul></ul>IB2 TAHBSO+PLND IB1 Complementary concurrent CT/RT if risk factors (LVSI, gr3) Conization / H+PLND IA2 Conservative surgery Conization/H+PLND* if LVSI IA1 Issue Recomended Stage
  8. 8. NIH Consensus Statement on Cervical Cancer Bethesda 1996 “ patients with stage IB and IIA cervical cancer are appropriately treated with either radical hysterectomy with pelvic lymphadenectomy or radiation therapy with equivalent result. To minimize morbidity, primary therapy should avoid the routine use of both radical surgery and radiation therapy.The combined use of radical surgery and radical radiation therapy results in high morbidity and cost.” Cervical Cancer
  9. 9. 2/22/99: NCI issues clinical announcement on cervical cancer <ul><li>The results of 5 large studies have shown that women with invasive cervical cancer have better survival when they receive chemotherapy which includes the drug cisplatin along with radiation therapy. </li></ul>Locally advanced cervical cancer
  10. 11. <ul><li>significant improvement (p<0.0001) of </li></ul><ul><ul><li>overall survival (> 6%) </li></ul></ul><ul><ul><li>overall disease free survival (8%) </li></ul></ul><ul><ul><li>local regional disease free survival (9%) </li></ul></ul><ul><ul><li>metastasis free survival (7%) </li></ul></ul><ul><li>greater effect for stage IB2-IIA/IIB </li></ul><ul><li>better results for platinum based therapy </li></ul>Concurrent chemoradiotherapy for cervical cancer a Meta-Analysis of 18 randomized trials Meta-Analysis Group, JCO, 2008 Cervical Cancer
  11. 12. <ul><li>“ strong consideration should be given to the incorporation of concurrent cisplatin based chemotherapy in women who require radiation therapy for treatment of cervical cancer” </li></ul>NCI Clinical Announcement on concurrent chemoradiation for cervical cancer - 1999 Cervical Cancer
  12. 13. <ul><li>Fertility sparing surgery in early stages: </li></ul><ul><li>radical trachelectomy + PLND (RT+PLND) in stages IA1, IA2, IB1 (if <2 cm tumor, no LVSI, no nodal involvement) </li></ul><ul><li>Adjuvant CT after combined CT/RT </li></ul><ul><li>Optimal CT for combination with EBRT+BRT </li></ul><ul><li>Benefit of concomitant CT/RT for stages III-IV </li></ul><ul><li>Neoadjuvant CT: EORTC 55994 (IB2-IIA-IIB) </li></ul>Pending issues Cervical Cancer
  13. 14. CONCLUSIONS CT/RT is considered the world standard treatment for LACC Neoadjuvant CT followed by surgery may represent an alternative: in two randomized trials TIP demonstrated a superior activity compared to IP and TP but was associated with significantly higher toxicity The cost-effectiveness of neoadjuvant CT followed by surgery will be tested in a randomized trial against CT/RT (EORTC 55994) .
  14. 15. 55994 EORTC Treatment scheme
  15. 16. Treatment <ul><li>Stage IVB </li></ul><ul><li>Recurrence not suitable for local treatment (pelvic and extrapelvic) </li></ul><ul><li>Chemotherapy </li></ul><ul><li>CTplatinum based with </li></ul><ul><li>PFS OS gr3 PLT </li></ul><ul><li>(mos) (mos) (%) </li></ul><ul><ul><ul><ul><ul><li>Topotecan 4.6 10 35 </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Paclitaxel 5.8 13 7 </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Gemcitabine 4.7 10 28 </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Vinorelbine 4 10 7 </li></ul></ul></ul></ul></ul><ul><li>Targeted agents </li></ul><ul><ul><ul><li>Cetuximab </li></ul></ul></ul><ul><ul><ul><li>Bevacizumab </li></ul></ul></ul>Cervical Cancer Monk, JCO, 2009
  16. 17. Bevacizumab in advanced cervical cancer <ul><li>Single agent in recurrent disease (GOG-227 C) </li></ul><ul><li>Four arm study in recurrent disease (GOG-0240) </li></ul><ul><ul><ul><li>paclitaxel + CisPt ± BEV </li></ul></ul></ul><ul><ul><ul><li>paclitaxel + Topotecan ± BEV </li></ul></ul></ul>OS and toxicity Cervical Cancer
  17. 18. Phase II trial of Bevacizumab in persistent/recurrent squamous cell carcinoma of the cervix - a GOG study <ul><li>46 pts, all with prior CT, prior RT in 56 % </li></ul><ul><li>BEV 15 mg/kg q3wks </li></ul><ul><li>Hypertension 15 % </li></ul><ul><li>TE 11 % </li></ul><ul><li>PR 11 % </li></ul><ul><li>Median PFS 3.4 mo </li></ul><ul><li>OS 7.3 mo </li></ul>JCO, 2009 PFS of non randomized GOG studies in cervical cancer Cervical Cancer
  18. 19. Bevacizumab in advanced cervical cancer <ul><li>Single agent in recurrent disease (GOG-227 C) </li></ul><ul><li>Four arm study in recurrent disease (GOG-0240) </li></ul><ul><ul><ul><li>paclitaxel + CisPt ± BEV </li></ul></ul></ul><ul><ul><ul><li>paclitaxel + Topotecan ± BEV </li></ul></ul></ul>OS and toxicity Cervical Cancer
  19. 20. <ul><li>In order to minimize morbidity, primary therapy should avoid the planned use of both radical surgery and radiation therapy. </li></ul><ul><li>The combined use of radical surgery and radical radiation therapy results in high morbidity and cost. </li></ul>NIH Consensus statement 1996 what is the optimal treatment of stage IB-IIA? Vol.14,n.1, April 1-3, 1996
  20. 21. <ul><li>19 randomized studies of RCT (2 not published) </li></ul><ul><ul><li>12 platinum based (+/- BLM, VCR, 5FU) </li></ul></ul><ul><ul><li>7 other drugs (MMC, 5FU, BLM, EADM) </li></ul></ul><ul><li>4580 patients </li></ul><ul><li>2865-3611 evaluable </li></ul>concurrent RCT meta-analysis Green JA et al., Lancet 358:781, 2001 LEVEL OF EVIDENCE = I

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