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Carcinoma della Cervice Uterina CronoprogrammaDiagnostico-Terapeutico.

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Presentation on theme: "Carcinoma della Cervice Uterina CronoprogrammaDiagnostico-Terapeutico."— Presentation transcript:

1 Carcinoma della Cervice Uterina CronoprogrammaDiagnostico-Terapeutico

2 Pap-test Anormale Bethesda System, 2001 L-SIL H-SIL

3 Pap-test Anormale

4 ASC-US61% L-SIL 31% H-SIL 8% ICC 0% ICC 0% Pap-test Anormale Davey, 2004

5 Solomon (ALTS Group), 2001 Stoler, 2001 Sherman, 2001 Kristen (ALTS Group), 2006 INCIDENCE: % CYTOLOGIC REVISION Downgraded to neg 40% Upgraded to L-SIL 20% Upgraded to H-SIL 2% Low reproducibility level Low PPV ASC-US NEGATIVE 75-85% RISK OF CIN2+ 12% RISK OF CIN3+ 5%

6 CIN 2-3Cancer Microinv. Inv. Microinv. Inv. ASC-US5-17 ASC-US 5-17 ASC-H24-94 ASC-H CIN CIN % Upgrading 0.2

7 ASC-US – HPV-test Triage SICPCV, 2006 HPV-test HR + HR - Colposcopia Pap-test a 12 mesi + - Colposcopia Screening

8 Statement on HPV DNA test utilization, 2009 HPV-test Triage – Raccomandazioni

9 p16 Triage (sperimentale) HPV-test (screening) HR - HR + p16-test + - Colposcopia HPV-test a un anno Carozzi, 2008

10 ASC-US - ASC-H - L-SIL SICPCV, 2006

11 H-SIL – Carcinoma squamocellulare SICPCV, 2006

12 AGC SICPCV, 2006

13 Citologia e colposcopia ogni 6 mesi per 2 anni Controllo annuale per altri 5 anni Ritorno a screening Follow-up SICPCV, 2006 Colposcopia, citologia e HPV-test Colposcopia e/o citologia + - Percorso sec. lesione Pap-test e HPV-test a 12 mesi + - Colposcopia Screening Colposcopia e/o citologia - HPV + Controllo a 6 mesi A 6 mesi da trattamento

14 Carcinoma squamoso in situ Carcinoma squamoso in situ Carcinoma squamoso inf. Carcinoma squamoso inf. cheratinizzante, non-cheratinizzante, verrucoso cheratinizzante, non-cheratinizzante, verrucoso Adenocarcinoma in situ / tipo endocerv. Adenocarcinoma in situ / tipo endocerv. Adenocarcinoma endometrioide Adenocarcinoma endometrioide Adenocarcinoma a cellule chiare Adenocarcinoma a cellule chiare Ca. adenosquamoso Ca. adenosquamoso Ca. adenoide cistico Ca. adenoide cistico Ca. a piccole cellule Ca. a piccole cellule Ca. indifferenziato Ca. indifferenziato Ca. neuroendocrino Ca. neuroendocrino Istotipi FIGO, 2006 ~10% ~80%

15 I The carcinoma is strictly confined to the cervix (extension to the corpus would be disregarded) IA Invasive carcinoma which can be diagnosed only by microscopy, with deepest invasion 5mm and largest extension 7mm IA1 Measured stromal invasion 3mm in depth and horizontal extension 7mm IA2 Measured stromal invasion >3mm and not >5mm with an extension of not >7mm IB Clinically visible lesions limited to the cervix or pre-clinical cancers > Stage IA IB1 Clinically visible lesion 4cm in greatest dimension IB2 Clinically visible lesion >4cm in greatest dimension II Cervical carcinoma invades beyond the uterus, but not to the pelvic wall or to the lower third of the vagina IIA Without parametrial invasion IIA1 Clinically visible lesion 4cm in greatest dimension IIA2 Clinically visible lesion >4cm in greatest dimension IIB With obvious parametrial invasion III The tumor extends to the pelvic wall and/or involves lower third of the vagina and/or causes hydronephrosis or non-functioning kidney IIIATumor involves lower third of the vagina (No extension to the pelvic wall) IIIB Extension to the pelvic wall and/or hydronephrosis or non-functioning kidney IV The carcinoma has extended beyond the true pelvis or has involved (biopsy proven) the mucosa of the bladder or rectum. A bullous edema, as such, does not permit a case to be allotted to Stage IV IVA Spread of the growth to adjacent organs IVB Spread to distant organs Cervical Cancer - FIGO Staging (2009)

16 Microinvasive CC IA Early CC IB1 IIA1 Locally Advanced CC (LACC) IB2 IIA2 IIB III IVA Metastatic CC IVB


18 FIGO IA1: stromal invasion 3 mm in depth, horizontal extension 7 mm IA2: stromal invasion 3-5 mm in depth, horizontal extension 7 mm SGO Stromal invasion 3 mm in depth, no LVSI Microcarcinoma – Staging Criteria

19 Microcarcinoma – Treatment Total abdominal or vaginal hysterectomy (if VAIN, appropriate cuff of vagina should be removed) Observation after cone biopsy (particularly if fertility is desired) FIGO, 2006 IA1 Modified RH (Type 2) and pelvic LND Consider extrafascial H and pelvic LND (if no LVSI) If fertility is desired: large cone biopsy + extra-perit. or lpsc pelvic LND rad. trachelectomy and extra-perit.or lpsc pelvic LND IA2 Mainly with Pap smears annually after two normal smears at 4 and 10 mos Follow-up

20 Cone: Positive margin

21 In patient with positive margins: Vaginal Strict Follow-Up Endocervical Repeat Conization or or Stromal Hysterectomy Microcarcinoma – Cone Positive Margin

22 Fertility-sparing surgery Cervical Cancer Radical Trachelectomy Eligibility criteria Dargent, % of cervical cancer in women <45y (10-15% during childbearing years) Vaginal Abdominal Laparoscopic Robotic Age < years & Strong fertility desire Diagnosis of invasive cancer (ideally, disease located primarily on the ectocervix) Exclusion of unfavorable histology Stage IA1 with LVSI, IA2, IB1<2 cm No evidence of pelvic N met and/or distant met Gynecologic oncologist experienced in laparoscopic and radical vaginal surgery

23 Fertility-sparing surgery RVT & Cancer prognosis Overall recurrence and death rates comparable to early-stage cervical cancer treated by RH or RT Plant, 2004; Seli, 2005 ReviewnRecurrence Rates Death Rates Darsun, Sonoda, Plante,

24 Fertility-sparing surgery RVT & Pregnancy outcome Pregnancy rate 70% 1 st -2 nd trimester loss 30% Review (16 studies: 355 RVT / 161 pregnancies) Boss, 2005 Pregnancy rate 62% TAB/EUP 5% 1 st -2 nd trimester loss 27% Deliveries <32 ws 12% Deliveries >37 ws 65% Currently pregnant 6% Review (8 studies : 603 RVT / 256 pregnancies) Plante, 2008

25 CK Conization Follow-up Margins + Repeat cone LVSI + Margins - Pelvic LND N + RH N - Follow-up No Res T Invasive Res T RH + pelvic LND Cerv Microca – Conservative Treatment Algorythm IA2 LVSI -

26 CERVICAL CARCINOMA Clinical Assessment Histotype & Grade Bladder/Rectum involvement Parametrial infiltration FIGO Stage Vaginal infiltration Lymphnode mets T size

27 Esame vaginale bimanuale e vagino-rettale (in narcosi) Colposcopia, biopsia / conizzazione Currettage endocervicale Cistoscopia Retto-sigmoidoscopia Rx torace (2 proiezioni) TAC/RMN (PET) FIGO, 2006 Stadiazione Clinica CC localmente avanzato CC apparentemente iniziale RX torace RMN addome/pelvi Visita ginecologica in narcosi RX torace RMN addome/pelvi Uretrocistoscopia Retto-sigmoidoscopia

28 Cervical Cancer Comparison of Diagnostic Procedure Utilization ACRIN 6651/GOG 183 (n=208 ;Stage IB) Cystoscopy 64%80% 52% 8.1% Sigmoidoscopy 44% 58% 49% 8.6% Barium enema 58% 60% 32% 0 Intravenous urogram 86% 91% 42% 1.0% Lymphangiography 18% 11% 14% 0 CT/MRI 16% 54% 70% 100% Montana, 1995 Amendola, 2005

29 Narayan K, 2003 MRI staging for cervical cancer is now widely accepted as an optimal method for evaluation of tumor volume, uterine corpus involvement, parametrial invasion, … Cervical Cancer MRI … but prediction of parametrial, bladder and rectal involvement is correct in 75% of cases at best Bipatt, 2003 Narayan, 2005 Follen, 2003

30 Cervical Cancer Detection of Advanced Stage (>IIB) Cancer by Retrospective Readers of CT & MRI ACRIN 6651/GOG 183 (n=208 – Stage IB) CTMRIP Value CTMRIP Value Mean sensitivity (%) Mean specificity (%) Mean PPV (%) Mean NPV (%) Hricak, 2007

31 Cervical Cancer Performance of CT & MRI in Detecting Lymph Node Involvement ACRIN 6651/GOG 183 (n=208 – Stage IB) CT MRI CT MRI Sensitivity (%) Specificity (%) Hricak, 2005

32 FIGO, 2006 Treatment – Stage IB1, IIA1 Modified RH (Type 2) or RH (Type 3) and pelvic LND Adjuvant pelvic RT plus BRT Adjuvant concurrent CTRT (Cisplatin±5FU) survival in such patients In younger patients, if post-operative radiation is likely to be given: ovaries may be preserved and suspended outside the pelvis

33 RH tipo III + LA pelvica + sampling N aortici RT pelvi + BRT Se desiderio di prole (solo per IB1): trachelectomia radicale + LA pelvica ± sampling N aortici NCCN, 2009 Treatment – Stage IB1-IIA1

34 Wertheim (1900) Okabayashi (1921) Meigs (1951) Nerve-sparing (1990s) Robotics (2000s) Piver-Rutledge (1974) Mota-EORTC (2008) Querleu-Morrow (2008) Radical Hysterectomy – History & Classification

35 Type I (Extrafascial hysterectomy): simple hysterectomy to remove the entire cervical tissue Type II (Modified RH): basically, the RH described by Wertheim, to remove more paracervical tissue while still preserving the blood supply to the distal ureters and bladder Type III (RH): first described by Meigs in 1944, with the purpose of a wide excision of parametrial and paravaginal tissue Type IV (Extended RH): complete removal of the periureteral tissue and a more extensive resection of the paravaginal tissue Type V (Partial exenteration): radical removal of disease involving the distal ureter and/or bladder Radical Hysterectomy – Piver-Rutledge Classification Piver, 1974



38 Type 3 RH Type 3 RH Type 2 RH

39 Radical Hysterectomy – Querleu-Morrow Classification Type A (Minimum resection of paracervix): extrafascial hysterectomy, corresponds to the type I RH, with a <10 mm vaginal resection Type B (Transection of paracervix at the ureter): corresponds to the type II RH, with (B2) or without (B1) additional removal of the lateral paracervical lymph nodes, and >10mm vaginal resection Type C (Transection of paracervix at junction with internal iliac vascular system): corresponds to type III RH, with the ureter completely mobilized, 15-20mm of vagina and corresponding paracolpos resected routinely; with (C1) or without (C2) autonomic nerve preservation Type D (Laterally extended resection): ultraradical procedures mostly indicated at the time of pelvic exenteration, with the entire paracervical resection at the pelvic sidewall including the hypogastric vessels (D1); type D2 includes the resection of adjacent fascial-muscular structures Querleu, 2008

40 It is recommended to include the following information in the operative report: All parts defining the type of RH (transection of paracervix and vagina, uterine artery) Surgical (fresh sample) and pathological (fixed sample) length of ventral, dorsal and lateral extent of paracervix resection Surgical/pathological minimum length of vagina resected Minimum distance between tumor and resection margins (when applicable) Quality control and results comparison in RH The term paracervix replaces others such as cardinal or Mackenrodts ligament, or parametrium, and includes that usually named as paracolpium Querleu, 2008

41 Type A Type B1 Type C2

42 Surgery-related Complications Rad. Hysterectomy (type III) + Pelvic Lymph % Severe Perioperative Compl % Early/Late Bladder/Rectal Disf. 75% vs 10% (III vs II) Temp. Bladder Disf. Literature Review


44 FIGO, 2006 LN Involvement by Stage

45 FIGO, 2006 Treatment – Stage IB2, IIA2 Primary CTRT Primary RH and pelvic LND + Adjuvant RT Neoadjuvant CTRT (3 courses of platinum based CT) + RH and pelvic LND ± Adjuvant post-operative CT or RT If positive common iliac or paraaortic nodes: extended field radiation should be considered

46 Treatment – Stage IIB Primary CTRT (RT plus BRT) Primary pelvic exenteration (Stage IVA not involving pelvic sidewall) If positive common iliac or paraaortic nodes: extended field radiation should be considered Primary CT (Cisplatin) Unclear impact of CT on palliation and survival FIGO, 2006 IIB-IVA IVB

47 RH tipo III + LA pelvica + sampling N aortici CTRT (RT pelvi + Cisplatino + BRT) CTRT (RT pelvi + Cisplatino + BRT) + isterectomia adiuvante IB2-IIA2 NCCN, 2009 Treatment – Stage IB2-IVA CTRT (RT pelvi + Cisplatino + BRT) IIB-IVA

48 RT pelvi (volume, invasione stromale, LVSI) ± CT(P) Follow-up N - RT pelvi + CT(P) ± BRT (margini vaginali +) N pelvici + Margini + Parametrio + NCCN, 2009 Terapia Adiuvante & Follow-up ogni 3 mesi (1° anno) ogni 4 mesi (2° anno) ogni 6 mesi (3-5° anno) annuali (> 6° anno) EO gen & gin Pap-test Rx Torace Laboratorio CT/MRI/PET ogni anno (opzionale) ogni 6 mesi (opzionali) su indicazione clinica

49 (Neo)adjuvant Setting


51 Italian Multicenter Randomized Study, 2001 NACT + Surgery vs Exclusive RT (LACC)

52 Stage IB2-IIB

53 Stage III

54 EndpointNr. of events / patient HR (p value) Survival DFS Loco-regional DFS Metastases-free survival 368/ / / / ( ) 0.68 (0.0001) 0.63 ( ) NACT & Radical Surgery (Locally Advanced Cervical Cancer) Review & Meta-analysis The absolute improvement in survival of 15% (8-21%) at 5- years obtained by NACT is of the same magnitude as that achieved with the standard cisplatin-based CTRT Cochrane Coll., 2009

55 EORTC Trial EORTC Trial Study Coordinators: S. Greggi G. Kenter F. Landoni IB2; IIA2; IIB Cervical Cancer (age 18-75) RANDOM NACT + Radical Surgery ExclusiveCTRT

56 Flow-Chart IR tipo B o C + LA pelvica o CTRT IB1 FU MRC - Parametri - N - RT MRC + parametri + N + Inf stroma cerv >90% CT +/- RT CTNA + IR tipo C + LA pelvica o CTRT IB2 - II CTRT o Pelvectomia + LA pelvica III - IVA CT sistemica IVB RMN addome / pelvi Colposcopia, Rx torace, SCC Ag, Visita gin. in narcosi, Cistoscopia e Rettoscopia Stadiazione clinica Ca invasivo FU IA1 (margini -) Vedi algoritmo dedicato IA2 Ca microinvasivo Conizzazione Cervicale Ca microinvasivoCa non definito / CIN III Biopsia cervicale Sospetto K cervice uterina

57 Carcinoma della Cervice non Radiotrattato 1° e 2° anno3° e 4° anno5° anno> 5° anno A 30 gg Ogni 3 mesi Ogni 6 mesi Ogni 12 mesi Visita ginecologicaXX X XX E.O. generaleXX X XX Colposcopia X X XX Pap-Test X X XX Rx torace X XX RMN addome-pelvi* X XX Urinocoltura (+ ev. Abg)XX X CA125 X X X SCC X X X Follow-up

58 Carcinoma della Cervice Radiotrattato 1° e 2° anno3° e 4° anno5° anno> 5° anno A 45 gg Ogni 3 mesi Ogni 6 mesi Ogni 12 mesi Visita ginecologicaXX X XX E.O. generaleXX X XX ColposcopiaXX X XX Pap-Test XX XX Rx torace X XX RMN addome-pelvi* XX XX Urinocoltura (+ ev. Abg)XX X CA125 X X X SCC X X X Rettoscopia XX *TAC addome/pelvi qualora RMN controindicata Follow-up

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