ROLE OF CHEMOTHERAPY IN
GYNAEC MALIGNANCIES

DR. R. RAJKUMAR M.D., D.M.
OVARIAN CANCER









Leading cause of death from gynecologic cancer
75% present in advanced stage
Improvement i...
OVARIAN CANCER – CLINICAL
FINDINGS







Usual features :
Abdomino –pelvic mass, ascites, left supraclavicular
lymp...
OVARIAN CANCER - EVALUATION










Detailed history and clinical exam
Pelvic exam including per rectal exam to...
OVARIAN CANCER - EVALUATION









Tumor markers:
CA 125 –most commonly elevated in 80% of serous tumors
not ele...
OVARIAN CANCER – TUMOR
MARKERS


Sr.VEGF levels



HE4 (human epididymis 4)-WFDC gene product
MCS-F in serum & ascitic f...
OVARIAN CANCER - IMAGING


USG abdomen with colour doppler study –
transvaginal sonography



Complex mass with increase...
Ultrasonography &
Colour Doppler
OVARIAN CANCER - IMAGING
CT SCAN abdomen & pelvis:







Extent of disease in upper abdomen
Helps to decide on prima...
CT Scan
OVARIAN CANCER - IMAGING



MRI abdomen – not superior to CTscan except in pregnant
women where USG is inconclusive



P...
OVARIAN CANCER - INVESTIGATIONS



UPPER GI SCOPY& COLONOSCOPY – NOT
INDICATED ROUTINELY



Symptoms s/o gastric disease...
EPITHELIAL OVARIAN
CANCER
DIAGNOSIS
Symptoms
Clinical Examination

Investigations
Ca125

USG

Imaging

Colour Doppler
FNAC...
OVARIAN CANCER STAGING
Stage I - Limited to ovaries
A. Unilateral ovary
B. Bilateral ovaries
C. Positive cytology
Stage II...
OVARIAN CANCER
FIGO STAGING SYSTEM
Stage

Description

Incidence

Survival

20%

73%

I

Confined to ovaries

II

Confined...
HOW TO PROCEED AFTER
INVESTIGATIONS ?


Decision to proceed directly to surgery is a clinical one – in
advanced stage :

...
HOW TO PROCEED AFTER
INVESTIGATIONS?



Operable tumors – laparotomy and proceed



Avoid percutaneous FNA of localised ...
WHO NEEDS NEOADJUVANT
CHEMOTHERAPY?


Presence of gross ascites,



huge fixed pelvi-abdominal mass,



nodules in POD
...


USG abdomen showing



extensive peritoneal,omental deposits and liver
sec, bilateral pleural effusion
CT SCAN FINDINGS







Diffuse peritoneal thickening(DPT) >4mm – involving
atleast 2 of the 5 areas
lateral colic gu...
FOR NEOADJUVANT CHEMOTHERAPY


Cytologic evidence of malignancy – ascitic fluid



FNA of the mass ( transvaginal –prefe...
OVARIAN CANCER SURGICAL
DEBULKING AND STAGING

Exploration

Biopsies
(Staging)

TAH/
BSO
Washings/
Ascites
(Staging)
TAH =...
Cytoreductive Surgery
 Goal is elimination of all tumor
• No gross residual (microscopic)
• Optimal (<1 cm)
• Suboptimal ...
Does Cytoreduction Matter?
Optimal Suboptimal
Response Rate

Clinical CR

95%

75%

Pathologic CR

50%

25%

Progression f...
PROGNOSTIC FACTORS










Volume of residual disease after surgery
Stage
Histologic subtype
Histologic grade
P...
PRIMARY TREATMENT OF OVARIAN
CANCER
Cyclophosphamide +
Cisplatin
STANDARD OF CARE

1995

1997

GOG 172 confirms IP
therapy...
FIRST-LINE THERAPY –
Standard Treatment Options

Surgery with maximum
cytoreduction effort <1cm
residual disease

Platinum...
CHEMOTHERAPY
• Standard front-line chemotherapy today is
carboplatin, AUC 6 to 7.5, paclitaxel 175
mg/m2 every 21 days for...
The Role of Paclitaxel in First-line
Therapy for Ovarian Carcinoma
Study

# Pts

377
GOG
1321 III suboptimal-IV

Median PF...
OVARIAN CARCINOMA:
CLINICAL COURSE
Interval
Cytoreduction
Diagnosis

Symptoms

Chemotherapy #1

Second-Look

Secondary
Cyt...
EPITHELIAL OVARIAN CANCER
PLAN OF MANAGEMENT

Stage III/IV
Resectable

Unresectable

Primary cytoreductive surgery (Max)

...
CHEMOTHERAPY – EARLY STAGE
DISEASE


High risk early stage:
stage I, gr III, Ic,any stage II



Stage Ia,Ib –gr I & II c...
Chemotherapy in advanced stage


GOG 111: paclitaxel+cisplatin superior to cisplatin +



cyclophosphamide
RR 73% vs 60%...
Chemotherapy in advanced stage


GOG 158,AGO,NETHERLANDS-DENMARK:
Carboplatin+paclitaxel vs cisplatin +paclitaxel is equi...
Disease Volume

Interventions to

Mortality?

Current point of diagnosis
and initiation of treatment

Prevention

Screenin...
Interventions to

Mortality?

 Prevention
– Pedigree Analysis
– Medical: Oral Contraceptives
– Surgical: Risk-Reducing Oo...
Screening – US and CA 125
“…there is no evidence available yet

that the current screening modalities
of CA 125 and ultras...
Goals of Treatment:
Relapsed Ovarian Cancer
• Prolong Survival
• Delay Time to Progression
• Control Disease-Related Sympt...
Surveillance Options for Ovarian
Cancer Patients in Remission
• Second-look laparotomy
• Physical examination
– Include pe...
Ovarian Cancer:
How is Relapse Defined?
• Continuous rise in CA-125
• CA-125 above 100
• Radiographic recurrence

• Sympto...
Effect of Platinum-Free Interval
on Response Rate
% Response to Second-line
Platinum Therapy
Platinum-Free
Interval (mos)
...
Ovarian Cancer at First Relapse
Definition of Sensitivity
P
R 0
3
I
M
A Refractory
R
Y
T
R
E
A
T
M
E
N
T

6

12

18

24
Mo...
Active Agents in Ovarian Cancer
FDA approved
Altretamine

Carboplatin

Cisplatin

Gemcitabine/
Carboplatin

Paclitaxel

Pe...
Tumor Mass

Secondary
Cytoreduction
• Controversial

• Inconsistent definitions
• Benefit appears confined
to patients lik...
Advanced Ovarian Cancer
Median Survival: 1975 - 2005

80

57
52

months

60

20

(optimal)
(optimal)

37
40

66

24
12

14...
FIGO staging system, 2009

Stage I
The carcinoma is strictly confined to the cervix
(extension to the corpus would be disr...
Cervical cancer
FIGO Stage I a
Microinvasive carcinoma (invasion ≤ 5 mm)
Recommended work-up
• Vaginal and rectal examinat...
Cervical cancer
FIGO Stage Ib - IIa
Squamocellular, Adenocarcinoma, Adenosquamous

Recommended work-up

Neccessary investi...
Cervical cancer
FIGO stage IIb- IV
Recommended work-up
• Vaginal and rectal examination, biopsy or endocervical curettage ...
Cervical cancer
- recurrence Recommended work-up
•• Vaginal and rectal examination, biopsy - histopathological confirmatio...
Cervical cancer
Squamocellular, Adenocarcinoma,
Adenosquamous

Recommended work-up

Neccessary investigations:
• Vaginal a...
Why are YOU here ???
Why am I here ???
Why are WE here ???
Courtallam ima  gynec onco ppt
Courtallam ima  gynec onco ppt
Courtallam ima  gynec onco ppt
Courtallam ima  gynec onco ppt
Courtallam ima  gynec onco ppt
Courtallam ima  gynec onco ppt
Courtallam ima  gynec onco ppt
Courtallam ima  gynec onco ppt
Courtallam ima  gynec onco ppt
Courtallam ima  gynec onco ppt
Courtallam ima  gynec onco ppt
Courtallam ima  gynec onco ppt
Upcoming SlideShare
Loading in …5
×

Courtallam ima gynec onco ppt

757 views
575 views

Published on

Published in: Health & Medicine
0 Comments
2 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
757
On SlideShare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
26
Comments
0
Likes
2
Embeds 0
No embeds

No notes for slide

Courtallam ima gynec onco ppt

  1. 1. ROLE OF CHEMOTHERAPY IN GYNAEC MALIGNANCIES DR. R. RAJKUMAR M.D., D.M.
  2. 2. OVARIAN CANCER         Leading cause of death from gynecologic cancer 75% present in advanced stage Improvement in 5yr survival – 36% in 1977 39% in 1986 45% in 2002 More effective chemotherapy options Surgical techniques
  3. 3. OVARIAN CANCER – CLINICAL FINDINGS       Usual features : Abdomino –pelvic mass, ascites, left supraclavicular lymph node Unusual presentations: Right supraclavicular or axillary lymph nodes with abdominal mass Isolated pleural effusion Isolated ascites without any ovarian mass
  4. 4. OVARIAN CANCER - EVALUATION          Detailed history and clinical exam Pelvic exam including per rectal exam to assess POD - EUA Endometrial biopsy in selected cases Complete blood counts Renal function tests Liver function tests Tumor markers Chest x ray & other imaging studies Genetic counseling
  5. 5. OVARIAN CANCER - EVALUATION         Tumor markers: CA 125 –most commonly elevated in 80% of serous tumors not elevated in 50% of early stage tumors, mucinous and clear cell carcinomas Not a reliable diagnostic test Post operatively ca125 levels –sensitive –to monitor response to chemo Normalization after 3 cycles –favorable outcome Nadir <10u/ml – favorable Useful in follow up for detecting recurrence CEA , CA 19-9 - mucinous tumors & in krukenbergs tumor
  6. 6. OVARIAN CANCER – TUMOR MARKERS  Sr.VEGF levels  HE4 (human epididymis 4)-WFDC gene product MCS-F in serum & ascitic fluid Proteomic spectral analysis of serum SELDI-TOF –MS : Surface enhanced laser desorption and ionization time of flight MS   
  7. 7. OVARIAN CANCER - IMAGING  USG abdomen with colour doppler study – transvaginal sonography  Complex mass with increased vascularity Ascites Enlarged para aortic nodal masses Omental and peritoneal deposits larger than 1cm Matted bowel loops    
  8. 8. Ultrasonography & Colour Doppler
  9. 9. OVARIAN CANCER - IMAGING CT SCAN abdomen & pelvis:      Extent of disease in upper abdomen Helps to decide on primary surgery or neoadjuvant chemotherapy Attachment of omentum to splenic hilum Disease/tumor nodules >2cm in mesentery, liver surface or parenchyma, diaphragm, gall bladder fossa, suprarenal para aortic nodes Pulmonary or pleural nodules
  10. 10. CT Scan
  11. 11. OVARIAN CANCER - IMAGING  MRI abdomen – not superior to CTscan except in pregnant women where USG is inconclusive  PET-CT scan : not for diagnosis  Useful in rec.disease with isolated CA125 elevation
  12. 12. OVARIAN CANCER - INVESTIGATIONS  UPPER GI SCOPY& COLONOSCOPY – NOT INDICATED ROUTINELY  Symptoms s/o gastric disease or lower GI symptoms or fecal occult blood positive 4% have associated GI malignancy    Mammography Genetic counseling in pts with positive family history
  13. 13. EPITHELIAL OVARIAN CANCER DIAGNOSIS Symptoms Clinical Examination Investigations Ca125 USG Imaging Colour Doppler FNAC contraindicated CT/MRI
  14. 14. OVARIAN CANCER STAGING Stage I - Limited to ovaries A. Unilateral ovary B. Bilateral ovaries C. Positive cytology Stage II - Limited to pelvis A. Extends to uterus or tubes B. other pelvic organs C. Positive cytology Stage III – Spread to upper abdomen or regional lymph nodes A. Microscopic spread B. Macroscopic < 2 cm C. Macroscopic > 2 cm liver metastases Stage IV - Spread outside peritoneum, pleura or parenchymal
  15. 15. OVARIAN CANCER FIGO STAGING SYSTEM Stage Description Incidence Survival 20% 73% I Confined to ovaries II Confined to pelvis 5% 45% III Confined to abdomen/ 58% lymph nodes 21% IV Distant metastases <5% 17% Jelic S, et al. Program and abstracts of the 27th Congress of the European Society for Medical Oncology; 2002; Nice, France. Mocharnuk R. Medscape Web site. http://www.medscape.com/viewarticle/444134. Accessed May 2, 2007. FIGO = International Federation of Gynecology and Obstetrics
  16. 16. HOW TO PROCEED AFTER INVESTIGATIONS ?  Decision to proceed directly to surgery is a clinical one – in advanced stage :  based on extent of disease  Performance status  Nutritional status  Comorbid illness
  17. 17. HOW TO PROCEED AFTER INVESTIGATIONS?  Operable tumors – laparotomy and proceed  Avoid percutaneous FNA of localised masses or complex cysts – upstage disease
  18. 18. WHO NEEDS NEOADJUVANT CHEMOTHERAPY?  Presence of gross ascites,  huge fixed pelvi-abdominal mass,  nodules in POD  PS III-IV  Supraclavicular nodes  Pleural effusion – bilateral
  19. 19.  USG abdomen showing  extensive peritoneal,omental deposits and liver sec, bilateral pleural effusion
  20. 20. CT SCAN FINDINGS      Diffuse peritoneal thickening(DPT) >4mm – involving atleast 2 of the 5 areas lateral colic gutters Lateral conal fascia Anterial abdominal wall Diaphragm and splenic peritoneal reflection Sean C.Dowdy et al, CANCER - 2004
  21. 21. FOR NEOADJUVANT CHEMOTHERAPY  Cytologic evidence of malignancy – ascitic fluid  FNA of the mass ( transvaginal –preferably)  Laparoscopy before NACT: - to assess disease extent and for biopsy in cases where repeated cytology is negative for malignancy
  22. 22. OVARIAN CANCER SURGICAL DEBULKING AND STAGING Exploration Biopsies (Staging) TAH/ BSO Washings/ Ascites (Staging) TAH = total abdominal hysterectomy BSO = bilateral salphingo-oophorectomy Goals (Debulking) • Assessment of extent of disease • Optimal tumor reduction
  23. 23. Cytoreductive Surgery  Goal is elimination of all tumor • No gross residual (microscopic) • Optimal (<1 cm) • Suboptimal (>1 cm)  Operative Technique • Resection of urinary or intestinal tract  Surgical Outcomes • Optimal in ~75% of cases • Does it matter?
  24. 24. Does Cytoreduction Matter? Optimal Suboptimal Response Rate Clinical CR 95% 75% Pathologic CR 50% 25% Progression free interval (mo) 34 13 Survival (mo) 50 36 10-yr survival 35% 15%
  25. 25. PROGNOSTIC FACTORS          Volume of residual disease after surgery Stage Histologic subtype Histologic grade Performance status Age Ovarian cancer prognostic profile(OCPP) Chemotherapy response profile (CRP) Gene expression profiling
  26. 26. PRIMARY TREATMENT OF OVARIAN CANCER Cyclophosphamide + Cisplatin STANDARD OF CARE 1995 1997 GOG 172 confirms IP therapy leads to a survival advantage compared with IV NEW STANDARD OF CARE? GOG 158 shows Taxol-carboplatin = TaxolCDDP, with improved toxicity and QoL 1999 2001 GOG 111 establishes Taxol-CDDP as standard 1st line SWOG 8501 demonstrates improved survival with IP therapy 2003 2005 2008 GOG 178 demonstrates improved DFS with longer duration of maintenance Taxol – No data on overall survival GOG 182 demonstrates no survival advantage to triplet or sequential doublet therapy
  27. 27. FIRST-LINE THERAPY – Standard Treatment Options Surgery with maximum cytoreduction effort <1cm residual disease Platinum + Taxane Chemotherapy (Carboplatin + Paclitaxel)
  28. 28. CHEMOTHERAPY • Standard front-line chemotherapy today is carboplatin, AUC 6 to 7.5, paclitaxel 175 mg/m2 every 21 days for 6 cycles • Result of several studies over last decade – GOG 1111 and OV 102 - paclitaxel/cisplatin vs cyclophosphamide/cisplatin – GOG 1583 and AGO OVAR-34 - carboplatin instead of cisplatin 1. McGuire WP, et al. N Engl J Med. 1996;334(1):1-6. 2. Piccart MJ, et al. J Natl Cancer Inst. 2000;92(9):699-708. 3. Ozols RF, et al. J Clin Oncol. 2003;21(17):3194-3200. 4. du Bois AD, et al. J Natl Cancer Inst. 2003;95(17):1320-1329. GOG = Gynecologic Oncology Group AGO = Arbeitsgemeinschaft Gynaekologische Onkologie
  29. 29. The Role of Paclitaxel in First-line Therapy for Ovarian Carcinoma Study # Pts 377 GOG 1321 III suboptimal-IV Median PFS (mo) Median OS (mo) Cisplatin/ Paclitaxel (24 h) x 6 14.1 26.3 Cisplatin 100 mg/m2 x 6 16.4 10.8 17.3 30.2 25.9 36.1 16.1 35.4 Regimen Paclitaxel 200 mg/m2 (24 h)* ICON 32 2074 I-IV *CR/PR rates on paclitaxel monotherapy (42%) vs cisplatin regimens (67%), P <.001 Carboplatin/ Paclitaxel (3 h) Carboplatin or CAP CAP = cyclophosphamide, doxorubicin, cisplatin GOG = Gynecologic Oncology Group ICON = International Collaborative Ovarian Neoplasm Group OS = overall survival PFS = progression-free survival 1. Muggia FM, et al. J Clin Oncol. 2000;18(1):106-115. 2. International Collaborative Ovarian Neoplasm Group. Lancet. 2002;360(9332):505-515.
  30. 30. OVARIAN CARCINOMA: CLINICAL COURSE Interval Cytoreduction Diagnosis Symptoms Chemotherapy #1 Second-Look Secondary Cytoreduction Progression Consolidation/ Maintenance Chemo #2 Cure Staging Primary cytoreduction Death Chemo #3+ Supportive Care
  31. 31. EPITHELIAL OVARIAN CANCER PLAN OF MANAGEMENT Stage III/IV Resectable Unresectable Primary cytoreductive surgery (Max) Chemo 3 cycles Chemo 6 cycles Interval cytoreductive Surgery (Max) Chemo 3 cycles
  32. 32. CHEMOTHERAPY – EARLY STAGE DISEASE  High risk early stage: stage I, gr III, Ic,any stage II  Stage Ia,Ib –gr I & II can be observed  ICON I(International Collborative Ovarian Neoplasm Trial I) &  ACTION (Adjuvant Chemotherapy in Ovarian Neoplasm Trial) –chemo improves progression free & OS in high risk early stage disease(925 pts – os – superior for platinum based chemo  GOG study -3 vs 6 cycles – 33% reduction in risk of rec in high risk disease who received 6cycles of chemo  Patients with suboptimal surgery benefit from platinum based chemo 
  33. 33. Chemotherapy in advanced stage  GOG 111: paclitaxel+cisplatin superior to cisplatin +  cyclophosphamide RR 73% vs 60%  Median PFS 18 vs 13mo  Median os 38mo vs 24mo p<001  60mo of follow up – 20% reduct. In risk of progression & 34% reduction in risk of death  OV10,ICON 3  GOG 132 –sequential administration of pacli or cisplatin is therapeutically equivalent
  34. 34. Chemotherapy in advanced stage  GOG 158,AGO,NETHERLANDS-DENMARK: Carboplatin+paclitaxel vs cisplatin +paclitaxel is equivalent – PFS &OS  Carbo+paclitaxel – preferred – favorable toxicity profile  Reduced emesis,neutropenia,nephrotoxicity  Short infusion time  Marginal PS,Comorbid medical condition – start with single agent carboplatin – add paclitaxel later  No benefit for 12 vs 6 cycles  No benefit for addition of 3rd cytotoxic agent – PLD,EPI,TOPO,GEM  Addition of bevacizumab 
  35. 35. Disease Volume Interventions to Mortality? Current point of diagnosis and initiation of treatment Prevention Screening Time
  36. 36. Interventions to Mortality?  Prevention – Pedigree Analysis – Medical: Oral Contraceptives – Surgical: Risk-Reducing Oophorectomy  Screening – Pelvic Examination – Ultrasonography – CA125 and other (OvaSure) Serum Testing – Proteomics (OvaCheckTM)
  37. 37. Screening – US and CA 125 “…there is no evidence available yet that the current screening modalities of CA 125 and ultrasonography can be effectively used for widespread screening to reduce mortality from ovarian cancer…” NIH Consensus Development Panel
  38. 38. Goals of Treatment: Relapsed Ovarian Cancer • Prolong Survival • Delay Time to Progression • Control Disease-Related Symptoms • Minimize Treatment-Related Symptoms • Maintain or Improve Quality of Life
  39. 39. Surveillance Options for Ovarian Cancer Patients in Remission • Second-look laparotomy • Physical examination – Include pelvic examination • CA-125 • Imaging – CT scan – MRI? – PET scan? CT = computed tomography MRI = magnetic resonance imaging PET = positron emission tomography
  40. 40. Ovarian Cancer: How is Relapse Defined? • Continuous rise in CA-125 • CA-125 above 100 • Radiographic recurrence • Symptomatic recurrence • Physical examination findings • Combination of above
  41. 41. Effect of Platinum-Free Interval on Response Rate % Response to Second-line Platinum Therapy Platinum-Free Interval (mos) Markman Gore Blackledge 10% 15% 29% 20% 63% 30% 94% 0-6 30% 17% 7-12 27% 13-18 33% 27% 19-24 >24 Non-Platinum Therapy 59% 57% Markman M, et al. J Clin Oncol. 1991;9(3):389-393. Gore ME, et al. Gynecol Oncol. 1990;36:207-211. Blackledge G, et al. Br J Cancer. 1989;59:650-653.
  42. 42. Ovarian Cancer at First Relapse Definition of Sensitivity P R 0 3 I M A Refractory R Y T R E A T M E N T 6 12 18 24 Months Resistant Sensitive “Very Sensitive” Defined as measurable recurrence, not biochemical (CA-125) recurrence
  43. 43. Active Agents in Ovarian Cancer FDA approved Altretamine Carboplatin Cisplatin Gemcitabine/ Carboplatin Paclitaxel Pegylated liposomal doxorubicin Topotecan Not FDA approved, compendium listed Chlorambucil Cyclophosphamide Docetaxel Doxorubicin Epirubicin Etoposide 5-FU/LV Gemcitabine Ifosfamide Irinotecan Melphalan Methotrexate Thiotepa Vinorelbine Not FDA approved, not compendium listed Aromatase inhibitors Tamoxifen Bevacizumab Pemetrexed
  44. 44. Tumor Mass Secondary Cytoreduction • Controversial • Inconsistent definitions • Benefit appears confined to patients likely to respond to additional chemo: • >12 month PFI • Isolated site of recurrence • Disease completely resectable PFI = progression-free interval Vena Cava Renal Vein Kidney Diaphragm Kidney Resected Liver
  45. 45. Advanced Ovarian Cancer Median Survival: 1975 - 2005 80 57 52 months 60 20 (optimal) (optimal) 37 40 66 24 12 14 0 1975 Alkeran 1983 1986 multi-drug 1996 1998 cisplatin 2003 paclitaxel 2005 IP therapy
  46. 46. FIGO staging system, 2009 Stage I The carcinoma is strictly confined to the cervix (extension to the corpus would be disregarded) Stage IA: Invasive carcinoma which can be diagnosed only by microscopy, with deepest invasion ≤5 mm and largest extension ≤7 mm Stage IA1: Measured stromal invasion of ≤3.0 mm in depth and extension of ≤7.0 mm. Stage IA2: Measured stromal invasion of >3.0 mm and ≤5.0 mm with an extension of not >7.0 mm Stage IB: Clinically visible lesions limited to the cervix uteri or pre-clinical cancers greater than stage IA* Stage IB1: Clinically visible lesion ≤4.0 cm in greatest dimension Stage IB2: Clinically visible lesion >4.0 cm in greatest dimension Stage II Cevical carcinoma invades beyond the uterus, but not to the pelvic wall or to the lower third of the vagina Stage IIA: Without parametrial invasion Stage IIA1: Clinically visible lesion ≤4.0 cm in greatest dimension Stage IIA2: Clinically visible lesion >4 cm in greatest dimension Stage IIB: With obvious parametrial invasion Stage III The tumor extends to the pelvic wall and/or involves lower third of the vagina and or causes hydronephrosis or non-functioning kidney** Stage IIIA: Tumor involves lower third of the vagina, with no extension to the pelvic wall Stage IIIB: Extension to the pelvic wall and/or hydronephrosis or non-functioning kidney Stage 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 Stage IVA: Spread of the growth to adjacent organs. Stage IVB: Spread to distant organs. *All macroscopically visible lesions—even with superficial invasion—are allotted to stage IB carcinomas. Invasion is limited to a measured stromal invasion with a maximal depth of 5.00 mm and a horizontal extension of not >7.00 mm. Depth of invasion should not be >5.00 mm taken from the base of the epithelium of the original tissue—superficial or glandular. The depth of invasion should always be reported in mm, even in those cases with “early (minimal) stromal invasion” (~1 mm). The involvement of vascular/lymphatic spaces should not change the stage allotment. ** On rectal examination, there is no cancer-free space between the tumor and the pelvic wall. All cases with hydronephrosis or non-functioning kidney are included, unless they are known to be due to another cause.
  47. 47. Cervical cancer FIGO Stage I a Microinvasive carcinoma (invasion ≤ 5 mm) Recommended work-up • Vaginal and rectal examination, exfoliative cytology (Papanicolaou smear), colposcopy, biopsy and/or endocervical curettage (ECC), conization or Loop electrosurgical procedure (LEEP) • Histopathological finding with all standard tumor parameters • Laboratory analyses: WBC, biochemical analyses • Imaging: Chest X-ray, pelvic and abdominal ulstrasound Diagnosis is based on conization! Conization Necessary HP parameters:2 • Depth of invasion • Width of the tumor • Tumor differentiaion • Lympho-vascular space invasion (LVSI) • Resection margins Margins clear ECC negative Stage Ia1 LVSI negative Conization if preservation of fertility is desired or Simple (extrafascial, type A6) hysterectomy with or without salpingoophorectomy Margins and/or ECC positive for dysplasia •Stage Ia1 with extensive LVSI Stage Ia2 • Repeated conisation • Modified radical hysterectomy (type B6) if re-conisation is not possible ± pelvic lymphadenectomy Conization or radical trachelectomy if preservation of fertility is desired or Modified radical hysterectomy (type B6) and Pelvic lymphadenectomy Recommended follow-up Every 3 months after completed therapy during the first year; every 6 months up to 5 years. Annually afterwards. Investigations in addition to gynaecological examination, including cytology and colposcopy, should be performed depending on symptoms, local findings and general condition of the patient
  48. 48. Cervical cancer FIGO Stage Ib - IIa Squamocellular, Adenocarcinoma, Adenosquamous Recommended work-up Neccessary investigations: • Vaginal and rectal examination, colposcopy, biopsy and/or endocervical curettage (ECC); conization or loop electrosurgical procedure (LEEP) if needed for definitive diagnosis • Histopathological finding with all standard tumor parameters • Laboratory analyses: WBC, biochemical analyses including check for renal function and Hb • Imaging: Chest X-ray, abdominal and pelvic ultrasound (size and position of the tumor and tumor volume/cervix ratio) Optional investigations: Pelvic NMR, CT of the abdomen (PET/CT if possible), cystoscopy, rectoscopy, IVU or sonographic renal examination. Involvement of the bladder or rectum should be confimed histologically Radical surgery Chemo-radiation or Neoadjuvant chemotherapy followed by radiation or surgery is an option for locally advanced tumors (Ib2 and IIa2) but awaits confirmatory evidence from controlled clinical trials. • Medical contra-indications for surgery • Ib2/IIa2 tumors in selected cases • Anterior vaginal extension • Invasive cancer after simple hysterectomy • Choice of the patient • Uterus with paracervical tissues and upper part of vagina (radical, type C6 hysterectomy) + pelvic lymphadenectomy or • Entire cervix with paracervical tissues (radical trachelectomy) if fertility is desired + pelvic lymphadenectomy or • Upper part of vaginal cuf, paracervical tissues + pelvic lymphnodes in case of previous simple hysterectomy * At least 2 cm distance from the resection margins is desirable ** In premenopausal women ovaries can be retained; if so tranposition is advised. *** For the desision of further management, all neccesary histopathologic parameters4 should be requested Negative nodes GOG score* *consider using GOG score as a guide for adjuvant treatment5 Low risk (GOG score < 120) Low risk (GOG score < 120) Follow up Radiation ± Chemotherapy • Positive nodes (1-3) • Poorly differentiated or undifferentiated tumor (G3) • LVSI present • Primary tumor (tumor-cervix volume) >3 cm • Endocervical invasion (barrel shaped cervix) • Inadequate surgery • Insufficient HP (if report of all necessary parts is missing) Radiation ± Chemotherapy • Positive resection margins • Involvement of parametria • Residual tumor • Multiple positive nodes (>3) Concomitant Chemo-radiation Recommended follow-up Every 3 months after completed therapy during the first year; every 6 months up to 5 years. Annually afterwards. Investigations in addition to gynaecological examination should be performed depending on symptoms, local findings and general condition of the patient
  49. 49. Cervical cancer FIGO stage IIb- IV Recommended work-up • Vaginal and rectal examination, biopsy or endocervical curettage (ECC) • Histopathological finding with all standard tumor parameters • Laboratory analyses: WBC, biochemical analyses including check for renal function and Hb • Imaging: Chest X-ray, abdominal and pelvic ultrasound • Pelvic NMR, CT of the abdomen (PET/CT if possible), cystoscopy, rectoscopy, IVU or sonographic renal examination. Involvement of the bladder or rectum should be confimed histologically Pelvic MRI and Abdominal CT Paraaortic nodes (PALN) negative (=not enlarged) Pelvic or paraaortic nodes (PALN) positive (enlarged ≥2 cm)) Pelvic (± paraaortic) radiation + brachytherapy + concomitant chemotherapy CT of the lungs & mediastinum CT negative Pelvic radiation (with paraaortic if PALN are positive) + brachytherapy + concomitant chemotherapy CT positive Palliative pelvic RT ± Palliative chemotherapy * Consider: • resection of adnexal mass and/or extraperitoneal resection of enlarged nodes • Sequential chemoth and Concomitant ChemoRadioTherapy /External Beam RadioTherapy (CCRT/EBRT) *Stage IVa • with vesicovaginal fistula: if pelvic, abdominal and chest imaging exclude distant metastases primary pelvic exenteration can be considered • NACT may be offered to large bulky tumors to downsize tumor prior to CCRT Recommended follow-up Every 3 months after completed therapy; every 6 months up to 5 years. Annually afterwards. Investigations in addition to gynaecological examination should be performed depending on symptoms, local findings and general condition of the patient
  50. 50. Cervical cancer - recurrence Recommended work-up •• Vaginal and rectal examination, biopsy - histopathological confirmation of recurrence • Laboratory analyses: WBC, biochemical analyses including check for renal function and Hb • Imaging: Chest X-ray, pelvic and abdominal ultrasound, pelvic NMR and CT of the lungs and abdomen; (PET/CT if possible) • Cystoscopy, rectoscopy, IVU or sonographic renal examination Lungs & abdominal CT Pelvic recurrence No previous radiation Options include: • Chemo-radiation • Neoadjuvant chemotherapy (NACT) • Supportive care Extrapelvic recurrence Previous radiation Central pelvic recurrence Options include • Radical hysterectomy in tumor <2 cm • Pelvic exenteration • Neoadjuvant chemotherapy (NACT) + surgery Other options if surgery is not possible: • Re-irradiation • Neoadjuvant chemotherapy (NACT) + radiation • Systemic therapy • Supportive care Sidewall pelvic recurrence Options include: • Palliative radiotherapy or chemo-radiation • Systemic therapy • Supportive care * Resection in selected cases (in particular paraaortic nodes) may be considered Options include: • Resection of isolated disease • Systemic therapy • Supportive care Recommended follow-up Every 3 months for two years or more often if clinically indicated. Every 4-6 months thereafter. Annually afterwards. Investigations in addition to gynaecological examination should be performed depending on symptoms, local findings and general condition of the patient
  51. 51. Cervical cancer Squamocellular, Adenocarcinoma, Adenosquamous Recommended work-up Neccessary investigations: • Vaginal and rectal examination, colposcopy, biopsy and/or endocervical curettage (ECC); conization or loop electrosurgical procedure (LEEP) if needed for definitive diagnosis • Histopathological finding with all standard tumor parameters • Laboratory analyses: WBC, biochemical analyses including including check for renal function and Hb • Imaging: Chest X-ray, abdominal and pelvic ultrasound (size and position of the tumor and tumor volume/cervix ratio) Optional investigations: • Pelvic NMR, CT of the abdomen (PET/CT if possible), cystoscopy, rectoscopy, IVU or sonographic renal examination. Involvement of the bladder or rectum should be confirmed histologically *Stage of the disease is determined using FIGO classification1 FIGO Ia FIGO Ib-IIa • Diagnosis is based on conization; resection margins should be clear • Further decision depends on the presence of poor histologic prognostic factors2 FIGO Ia1 LVSI negative • Conization or • Simple hysterectomy (type A6) Follow-up Surgery Chemo-radiation • Medical contra-indications for surgery • Ib2/IIa tumors • Anterior vaginal extension • Invasive cancer after simple hysterectomy • Choice of the patient FIGO Ia1, LVSI positive • Conization/radical trachelectomy or • Modified radical hysterectomy(type B6) and • Pelvic Lymphadenectomy or FIGO IIb-IV • Radical hysterectomy (type C6) or • Radical trachelectomy or • Resection of the upper part of vagina and parametrectomy in case of previous simple hysterectomy and • Pelvic lymphadenectomy * Decision about further therapy is based on the presence of adverse histological factors No adverse prognostic factors Follow-up Concomitant chemoradiation or Radical radiation only if unfit for chemotherapy * Stage IV1 with vesicovaginal fistula: if pelvic, abdominal and chest CT exclude distant metastases, primary pelvic exenteration can be considered Neoadjuvant chemotherapy followed by radiation or surgery is an option for locally advanced tumors, but awaits confirmatory evidence from controlled clinical trials. Adverse prognostic factors4 present Adjuvant therapy (Radiation ± Chemotherapy) Recommended follow-up Every 3 months after completed therapy during the first year; every 6 months up to 5 years. Annually afterwards. Investigations in addition to gynaecological examination should be performed depending on symptoms, local findings and general condition of the patient
  52. 52. Why are YOU here ???
  53. 53. Why am I here ???
  54. 54. Why are WE here ???

×