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Courtallam ima  gynec onco ppt Courtallam ima gynec onco ppt Presentation Transcript

  • 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 in 5yr survival –  36% in 1977  39% in 1986  45% in 2002  More effective chemotherapy options  Surgical techniques
  • 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
  • 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
  • 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
  • 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
  • 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
  • Ultrasonography & Colour Doppler
  • 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
  • CT Scan
  • 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
  • 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
  • EPITHELIAL OVARIAN CANCER DIAGNOSISSymptoms Clinical Examination Investigations Ca125 Imaging USG Colour Doppler CT/MRI FNAC contraindicated
  • 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 Stage IV - Spread outside peritoneum, pleura or parenchymalliver metastases
  • OVARIAN CANCER FIGO STAGING SYSTEM Stage Description Incidence Survival I Confined to ovaries 20% 73% II Confined to pelvis 5% 45% III Confined to abdomen/ 58% 21% lymph nodes IV Distant metastases 17% <5% 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
  • 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
  • HOW TO PROCEED AFTER INVESTIGATIONS?  Operable tumors – laparotomy and proceed  Avoid percutaneous FNA of localised masses or complex cysts – upstage disease
  • WHO NEEDS NEOADJUVANT CHEMOTHERAPY?  Presence of gross ascites,  huge fixed pelvi-abdominal mass,  nodules in POD  PS III-IV  Supraclavicular nodes  Pleural effusion – bilateral
  •  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 gutters  Lateral conal fascia  Anterial abdominal wall  Diaphragm and splenic peritoneal reflection Sean C.Dowdy et al, CANCER - 2004
  • 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
  • OVARIAN CANCER SURGICAL DEBULKING AND STAGING Exploration Washings/ Ascites (Staging) TAH/ BSO Biopsies (Staging) Goals (Debulking) •Assessment of extent of disease •Optimal tumor reduction TAH = total abdominal hysterectomy BSO = bilateral salphingo-oophorectomy
  • 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?
  • 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%
  • 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
  • PRIMARY TREATMENT OF OVARIAN CANCER 1995 1997 1999 Cyclophosphamide + Cisplatin STANDARD OF CARE GOG 111 establishes Taxol-CDDP as standard 1st line 2001 GOG 158 shows Taxol-carboplatin = Taxol- CDDP, with improved toxicity and QoL GOG 178 demonstrates improved DFS with longer duration of maintenance Taxol – No data on overall survival GOG 172 confirms IP therapy leads to a survival advantage compared with IV NEW STANDARD OF CARE? SWOG 8501 demonstrates improved survival with IP therapy 2003 2005 2008 GOG 182 demonstrates no survival advantage to triplet or sequential doublet therapy
  • FIRST-LINE THERAPY – Standard Treatment Options Platinum + Taxane Chemotherapy (Carboplatin + Paclitaxel) Surgery with maximum cytoreduction effort <1cm residual disease
  • 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
  • The Role of Paclitaxel in First-line Therapy for Ovarian Carcinoma Study # Pts Regimen Median PFS (mo) Median OS (mo) GOG 1321 377 III suboptimal-IV Cisplatin/ Paclitaxel (24 h) x 6 14.1 26.3 Cisplatin 100 mg/m2 x 6 16.4 30.2 Paclitaxel 200 mg/m2 (24 h)* 10.8 25.9 ICON 32 2074 I-IV Carboplatin/ Paclitaxel (3 h) 17.3 36.1 Carboplatin or CAP 16.1 35.4 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. *CR/PR rates on paclitaxel monotherapy (42%) vs cisplatin regimens (67%), P <.001
  • OVARIAN CARCINOMA: CLINICAL COURSE Symptoms Diagnosis Chemotherapy #1 Staging Primary cytoreduction Interval Cytoreduction Progression Chemo #2 Chemo #3+ Supportive Care Death Consolidation/ Maintenance Cure Secondary CytoreductionSecond-Look
  • EPITHELIAL OVARIAN CANCER PLAN OF MANAGEMENT Resectable Primary cytoreductive surgery (Max) Chemo 6 cycles Unresectable Chemo 3 cycles Interval cytoreductive Surgery (Max) Chemo 3 cycles Stage III/IV
  • 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
  • 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
  • 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
  • Interventions to  Mortality? Time DiseaseVolume Prevention Screening Current point of diagnosis and initiation of treatment
  •  Prevention – Pedigree Analysis – Medical: Oral Contraceptives – Surgical: Risk-Reducing Oophorectomy  Screening – Pelvic Examination – Ultrasonography – CA125 and other (OvaSure) Serum Testing – Proteomics (OvaCheckTM) Interventions to  Mortality?
  • NIH Consensus Development Panel “…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…” Screening – US and CA 125
  • 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
  • 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
  • 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
  • Effect of Platinum-Free Interval on Response Rate % Response to Second-line Platinum Therapy Platinum-Free Interval (mos) Markman Gore Blackledge 0-6 17% 10% 7-12 27% 29% 13-18 33% 27% 63% 19-24 94% >24 59% 57% Non-Platinum Therapy 15% 20% 30% 30% 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.
  • Refractory P R I M A R Y T R E A T M E N T Resistant Sensitive 0 3 6 12 18 24 Months “Very Sensitive” Ovarian Cancer at First Relapse Definition of Sensitivity Defined as measurable recurrence, not biochemical (CA-125) recurrence
  • 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 Bevacizumab Pemetrexed Tamoxifen
  • 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 Kidney Resected Liver Diaphragm Kidney Vena Cava Tumor Mass Renal Vein PFI = progression-free interval
  • Advanced Ovarian Cancer cisplatin paclitaxelmulti-drugAlkeran Median Survival: 1975 - 2005 IP therapy (optimal) (optimal) months 12 14 24 37 52 57 66 0 20 40 60 80 1975 1983 1986 1996 1998 2003 2005
  • 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 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 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. Stage II Stage I FIGO staging system, 2009 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 Stage IV *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.
  • Diagnosis is based on conization! 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 ConizationNecessary HP parameters:2 • Depth of invasion • Width of the tumor • Tumor differentiaion • Lympho-vascular space invasion (LVSI) • Resection margins Margins and/or ECC positive for dysplasia Margins clear ECC negative Stage Ia1 LVSI negative •Stage Ia1 with extensive LVSI Stage Ia2 • Repeated conisation • Modified radical hysterectomy (type B6) if re-conisation is not possible ± pelvic lymphadenectomy Conization if preservation of fertility is desired or Simple (extrafascial, type A6) hysterectomy with or without salpingoophorectomy 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 Cervical cancer FIGO Stage I a Microinvasive carcinoma (invasion ≤ 5 mm)
  • 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 • 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 Chemo-radiation 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. 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 • Positive resection margins • Involvement of parametria • Residual tumor • Multiple positive nodes (>3) • 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) • Medical contra-indications for surgery • Ib2/IIa2 tumors in selected cases • Anterior vaginal extension • Invasive cancer after simple hysterectomy • Choice of the patient Concomitant Chemo-radiation Radiation ± Chemotherapy Radiation ± Chemotherapy Follow up Negative nodes GOG score* *consider using GOG score as a guide for adjuvant treatment5 Low risk (GOG score < 120) Low risk (GOG score < 120) or Cervical cancer FIGO Stage Ib - IIa Squamocellular, Adenocarcinoma, Adenosquamous
  • 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 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 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 CT positive Pelvic radiation (with paraaortic if PALN are positive) + brachytherapy + concomitant chemotherapy * Consider: • resection of adnexal mass and/or extraperitoneal resection of enlarged nodes • Sequential chemoth and Concomitant ChemoRadioTherapy /External Beam RadioTherapy (CCRT/EBRT) Palliative pelvic RT ± Palliative chemotherapy *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 Cervical cancer FIGO stage IIb- IV
  • 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 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 Lungs & abdominal CT Pelvic recurrence Extrapelvic recurrence Options include: • Palliative radiotherapy or chemo-radiation • Systemic therapy • Supportive care * Resection in selected cases (in particular paraaortic nodes) may be considered Previous radiationNo previous radiation Options include: • Chemo-radiation • Neoadjuvant chemotherapy (NACT) • Supportive care Central pelvic recurrence Sidewall 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 Options include: • Resection of isolated disease • Systemic therapy • Supportive care Cervical cancer - recurrence -
  • 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 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 FIGO Ia FIGO Ib-IIa FIGO IIb-IV • Diagnosis is based on conization; resection margins should be clear • Further decision depends on the presence of poor histologic prognostic factors2 Surgery Chemo-radiation 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 • Medical contra-indications for surgery • Ib2/IIa tumors • Anterior vaginal extension • Invasive cancer after simple hysterectomy • Choice of the patient • 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 Neoadjuvant chemotherapy followed by radiation or surgery is an option for locally advanced tumors, but awaits confirmatory evidence from controlled clinical trials. FIGO Ia1 LVSI negative • Conization/radical trachelectomy or • Modified radical hysterectomy(type B6) and • Pelvic Lymphadenectomy • Conization or • Simple hysterectomy (type A6) Follow-up No adverse prognostic factors Adverse prognostic factors4 present Follow-up Adjuvant therapy (Radiation ± Chemotherapy) FIGO Ia1, LVSI positive or Cervical cancer Squamocellular, Adenocarcinoma, Adenosquamous
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