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Carcinoma della Cervice Uterina Diagnostico-Terapeutico

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

1 Carcinoma della Cervice Uterina Diagnostico-Terapeutico
Cronoprogramma Diagnostico-Terapeutico 10’

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

3 Pap-test Anormale

4 Pap-test Anormale H-SIL 8% ICC  0% L-SIL 31% ASC-US 61% Davey, 2004

5 ASC-US INCIDENCE: 1.3-5.0% NEGATIVE 75-85% RISK OF CIN2+ 12%
CYTOLOGIC REVISION Downgraded to neg % Upgraded to L-SIL % Upgraded to H-SIL % Low reproducibility level Low PPV NEGATIVE % RISK OF CIN % RISK OF CIN % Solomon (ALTS Group), 2001 Stoler, 2001 Sherman, 2001 Kristen (ALTS Group), 2006

6 % Upgrading CIN 2-3 Cancer Microinv. Inv. ASC-US 5-17 ASC-H 24-94

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

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

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 Follow-up Citologia e colposcopia ogni 6 mesi per 2 anni
Controllo annuale per altri 5 anni Ritorno a screening A 6 mesi da trattamento 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 SICPCV, 2006

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

15 Cervical Cancer - FIGO Staging (2009)
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 IIIA Tumor 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

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


18 Microcarcinoma – Staging Criteria
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

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) 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 Follow-up Mainly with Pap smears annually after two normal smears at 4 and 10 mos FIGO, 2006

20 Cone: Positive margin

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

22 Fertility-sparing surgery
Cervical Cancer 43% of cervical cancer in women <45y (10-15% during childbearing years) Vaginal Abdominal Laparoscopic Robotic Radical Trachelectomy Eligibility criteria 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 Dargent, 1994

23 Fertility-sparing surgery
RVT & Cancer prognosis Review n Recurrence Rates Death Rates Darsun, 2007 520 4.2 2.8 Sonoda, 2008 548 4.0 2.6 Plante, 2008 603 4.5 2.5 Overall recurrence and death rates comparable to early-stage cervical cancer treated by RH or RT Plant, 2004; Seli, 2005

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

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

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

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

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

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

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

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

32 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 FIGO, 2006

33 Treatment – Stage IB1-IIA1
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

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

35 Radical Hysterectomy – Piver-Rutledge Classification
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 Piver, 1974


37 37

38 Type 3 RH Type 2 RH Type 3 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 Quality control and results comparison in RH
The term paracervix replaces others such as cardinal or Mackenrodt’s ligament, or parametrium, and includes that usually named as paracolpium 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) Querleu, 2008

41 Type A Type B1 Type C2

42 Rad. Hysterectomy (type III) + Pelvic Lymph.
Surgery-related Complications Rad. Hysterectomy (type III) + Pelvic Lymph. 10-15% Severe Perioperative Compl. 20-30% Early/Late Bladder/Rectal Disf. 75% vs 10% (III vs II) Temp. Bladder Disf. Literature Review 42 42


44 LN Involvement by Stage
FIGO, 2006

45 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 FIGO, 2006

46 Unclear impact of CT on palliation and survival
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 IIB-IVA Primary CT (Cisplatin) Unclear impact of CT on palliation and survival IVB FIGO, 2006

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

48 Terapia Adiuvante & Follow-up
N pelvici + Margini + Parametrio + RT pelvi + CT(P) ± BRT (margini vaginali +) RT pelvi (volume, invasione stromale, LVSI) ± CT(P) Follow-up N - 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 ogni anno (opzionale) Laboratorio ogni 6 mesi (opzionali) CT/MRI/PET su indicazione clinica NCCN, 2009

49 (Neo)adjuvant Setting


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

52 Stage IB2-IIB 52

53 Stage III 53

54 Review & Meta-analysis
NACT & Radical Surgery (Locally Advanced Cervical Cancer) Review & Meta-analysis Endpoint Nr. of events / patient HR (p value) Survival DFS Loco-regional DFS Metastases-free survival 368/872 414/872 402/872 381/872 0.65 ( ) 0.68 (0.0001) 0.63 ( ) 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 NACT + Radical Surgery Exclusive CTRT
EORTC Trial 55994 Study Coordinators: S. Greggi G. Kenter F. Landoni Cervical Cancer (age 18-75) IB2; IIA2; IIB RANDOM NACT + Radical Surgery Exclusive CTRT

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

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

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

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