Cervical Cancer

Assoc. Professor of Gynecologic Oncology Tata Memorial Hospital Amita Maheshwari Assoc. Professor of Gynecologic Oncology Tata Memorial Hospital maheshwariamita@yahoo.com

Cervical Cancer: Epidemiology Globally cervical cancer is the second most cancer among women 5,00,000 new cases & 2,75,000 deaths/year 10% of all cancer related deaths in women The most common cancer in women in India ~1,32,000 new cases / year and 74-100 deaths / year Every 7 minutes a woman dies of cervical cancer

Staging of cervical cancer FIGO (2008) Staging For Cervical Cancer: Clinical staging using examination under anesthesia, standard basic radiology including X-ray chest. Value of modern radiological investigations: CT scan:- R-P lymph nodes. High specificity and low sensitivity. MRI:- Equal to CT scan for R-P evaluation. More accurate for assessment of cervical tumor and surrounding tissue. PET scan:- More accurate to detect LN metastases.

FIGO Staging Stage I Carcinoma confined to cervix Stage IA1 Stromal invasion upto 3mm in depth &  7mm in width. Stage IA2 Stromal invasion 3-5 mm in depth &  7mm in width. Stage IB Clinical lesions confined to the cervix or pre-clinical lesions >stage IA2 Stage IB1 Lesions  4 cm Stage IB2 Lesions > 4 cm FIGO 2008

FIGO Staging…. FIGO stage Definition Stage IIA Involvement of upper 2/3rd of vagina Stage IIA1 Lesions  4 cm Stage IIA2 Lesions > 4 cm Stage II B Involvement of medial parametrium Stage IIIA Involvement of lower 1/3rd of vagina Stage IIIB Involvement of para upto LPW/HN Stage IVA Bladder &/or bowel involvement Stage IVB Distant metastasis

Basic Principles of Management of Cervical Cancer All stages of cervical cancer can be treated by radiation therapy Concurrent chemo-radiation is superior to radiation alone FIGO stages I-IIA cervical cancer are amenable to primary surgical treatment Adjuvant Rx may be required after Sx

Surgical Management of Ca-Cervix St.-IA1 Class-I Simple Hysterectomy Radical Trachelectomy Radical Cone St.-IA2 Class-II Modified Rad. Hyst.+BPLND Radical Trachelectomy St.IB1 Class-III Rad. Hyst. + BPLND Radical Trachelectomy (< 2 cm) St.IB2/IIA Class-III Rad. Hyst. +BPLND

Five classes of hysterectomy (Piver, 1974) Extent of Surgery Five classes of hysterectomy (Piver, 1974) Class Type of Surgical margins Indications Hysterectomy I Extrafascial No vagina, parametia FIGO stage IA1 no ureteric mobilization without LVSI II Modified Mid portion of uterosacral FIGO stage IA2, Radical & cardinal ligaments, IA1 with LVSI 1-2 cm of vagina III Radical All uterosacral & cardinal FIGO stage IB-IIA ligaments, 1/3rd of vagina,

Extent of Hysterectomy Class-I Class-II Class-III

Five classes of hysterectomy (Piver, 1974) cont.. Extent of Surgery Five classes of hysterectomy (Piver, 1974) cont.. Class Type of Surgical margins Indications Hysterectomy IV Radical ureter completely dissected Recurrent disease from cervico-vesical ligament superior vesicle art. sacrificed 3/4th of vagina, , V Radical Resection includes portion Recurrent disease of distal ureter and bladder

Pelvic LN Metastasis in Early Cervical Ca Stage IA1 <0.5% Stage IA2 8% (0-13%) Stage IB 12-20% Stage IIA 20-38%

Post-operative Morbidity Febrile morbidity Bladder dysfunction Fistulae – VVF, UVF Ureteric stenosis Neuropathies Thrombo-embolism Lymphocele Lower limb edema GI complications

Prognostic Factors & Adjuvant Rx Lymph node metastases Parametrial involvement Positive surgical margins Deep stromal invasion Lymph-vascular space invasion (LVSI) Tumor size > 4 cm

Adjuvant Treatment after RH Risk factors Risk category Adjuvant Rx Nil Low Risk None Deep stromal invasion Tumor >4 cm LVSI +ve Intermediate Risk Adjuvant pelvic RT* Lymph node +ve Cut margin +ve Parametrium +ve High Risk Adjuvant Concurrent CT + RT ** any two any one *Sedlis et al. Gynecol Oncol.1999 **Peters et al. J Clin Oncol.2000

Fertility Preserving Surgeries Radical resection of the primary tumor with an adequate clear margin +/- lymphadenectomy Types of surgery Stage of the disease Conization Stage IA1 without LVSI Conization with BPLND Stage IA1 with LVSI Radical Trachelectomy with BPLND Stages IA2-IB1, IA1 with LVSI Trachelectomy Lymphadenectomy Vaginal Abdominal Laparoscopic Extra-peritoneal

Radical Trachelectomy - Dargent et al (1994) described the technique. Eligibility criteria: Desire to preserve fertility. Upto FIGO stages IB1( <2cm). Limited endo-cervical involvement. No evidence of pelvic lymph node metastasis.

Radical trachelectomy.. Pelvic lymphadenectomy Frozen section Negative Nodes Radical trachelectomy If resection margins positive / nodes positive Radical hysterectomy Cervical circlage suture to ↓ the risk of abortion.

Radical trachelectomy- Obstetric considerations Contraception for 6-12 mths. ↑second trimester abortions, premature rupture of membrane, choriamnionitis, and preterm deliveries. Delivery by elective classical caesarean section.

Radical Vaginal Trachelectomy- Global data Authors Total No Pregnancies No. of Rec. Deaths births Shepherd 95 43 26 3 1 Dargent 96 55 36 4 3 Covens 80 22 12 7 0 Roy 66 37 24 2 1 Schneider 36 07 04 1 0 Burnett 21 03 03 1 0 Schlaerth 12 04 04 0 0 TOTAL 406 171 109 18(4.4%) 5(1.2%)

Ovarian Preservation & Transposition Risk of Ovarian Metastases in Early Cervical Ca: SCC 0.5% (4/770) Adenocarcinoma 1.7% (2/121) Adeno-squamous 0 (0/99) Sutton et al. Am J Obstet Gynecol. 1992

Ovarian Transposition Ovaries are detached from the uterus along with its blood supply and transposed in an area away from the radiation field, generally in the para-colic gutters abovethe pelvic brim. Drawbacks of Ovarian Transposition:- 25% risk of benign ovarian cysts. 50% ovarian failure. Risk of occult metastasis

Role of Sentinel Node Mapping First draining lymph node of an anatomical region Helps in tailoring the extent of surgery. Techniques: Peri-tumoral injection of blue dye and/or radioactive tracer. Extensively used in melanoma, breast and vulvar Ca. Still experimental in Cervical Cancer!

Role of minimally invasive surgery in the management of cervical cancer Laparoscopic Radical Hysterectomy (LRH). Laparoscopic Assisted Radical Vaginal Hysterectomy (LARVH). Laparoscopic surgical staging.

Chemo-Radiotherapy in Ca Cervix Combination of CT and RT is superior to RT alone. Chemotherapy: Cisplatin 40mg/m2/wk X 5-6 wks Radiation therapy: Combination of TELETHERAPY & BRACHYTHERAPY TELETHERAPY (EXTERNAL BEAM RADIATION THERAPY) BRACHYTHERAPY (INTERNAL RADIATION) INTRACAVITARY LDR HDR INTERSTITIAL LDR HDR

RECOMMENDED TOTAL RADIOTHERAPY DOSES 85-90 35-40 50 IIIB 85 45-50 IIB 75-80 30-35 45 IB/IIA 50-60 IA TOTAL DOSE ‘A’ ICRT-LDR POINT ‘A’ EXT. RT PELVIS Stage RADIOTHERAPY TREATMENT TO BE COMPLETED WITHIN 8 WKS IJROBP 1993,1995,

INTERSTITIAL BRACHYTHERAPY IN CERVIX INDICATIONS: Extensive Parametrial Disease Narrow/distorted vagina Post-hystercetomy Recc. Distal Vaginal involvement Persistent disease after radical radiotherapy (EXT + ICA) Applicators: Syed-Neblett Template (LDR) Martinez Universal Perineal Interstitial Template (MUPIT-HDR)

Management of Ca-Cervix EARLY I-IIA ADVANCED IIB – IVA IVA-IVB / REC SURGERY PALLIATION RADICAL RADIOTHERAPY + CHEMOTHERAPY RADIOTHERAPY CHEMOTHERAPY

Conclusions All stages can be treated with RT Concurrent CT-RT is superior to RT alone Surgery is the treatment of choice for early-stage cervical cancer. Adjuvant treatment is recommended in patients with poor prognostic factors. Preservation of fertility is possible in selected patients.