The Management of Cervical Cancer PowerPoint Presentation

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The Management of Cervical , Vulvar and Vaginal Cancers Kerry J. Rodabaugh, M.D. Division of Gynecologic Oncology University of Nebraska Medical Center

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Incidence: global public health issue 450,000 – 500,000 women diagnosed each year worldwide In developing countries, it is the most common cause of cancer death 340,000 deaths in 1985

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United States Incidence 15,000 women diagnosed annually 4,800 annual deaths

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Mortality Rates <2/100,000: Finland, France, Greece, Israel, Japan, Korea, Spain, Thailand 2.7/100,000: USA 12-15.9/100,000: Chile, Costa Rica, Mexico

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Lifetime risk of developing cervical cancer 5% - South America 0.7% - USA

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Cervical CA Risk Factors Early age of intercourse Number of sexual partners Smoking Lower socioeconomic status High-risk male partner Other sexually transmitted diseases Up to 70% of the U.S. population is infected with HPV

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Screening Guidelines for the Early Detection of Cervical Cancer, American Cancer Society 2003 Screening should begin approximately three years after a women begins having vaginal intercourse, but no later than 21 years of age. Screening should be done every year with regular Pap tests or every two years using liquid-based tests. At or after age 30, women who have had three normal test results in a row may get screened every 2-3 years. However, doctors may suggest a woman get screened more if she has certain risk factors, such as HIV infection or a weakened immune system. Women 70 and older who have had three or more consecutive Pap tests in the last ten years may choose to stop cervical cancer screening. Screening after a total hysterectomy (with removal of the cervix) is not necessary unless the surgery was done as a treatment for cervical cancer. American Cancer Society. Cancer Facts & Figures. 2004. Atlanta, GA; 2005

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Pap Smear Single Pap false negative rate is 20%. The latency period from dysplasia to cancer of the cervix is variable. 50% of women with cervical cancer have never had a Pap smear. 25% of cases and 41% of deaths occur in women 65 years of age or older.

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Clinical Presentation CIN/CIS/ACIS – asymptomatic Irregular vaginal bleeding Vaginal discharge Pelvic pain Leg edema Bowel/bladder symptoms

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Physical Findings Exophytic, cauliflower like mass Cervical ulcer, friable or necrotic Firm “barrel-shaped” cervix Hydronephrosis Anemia Weight loss

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Histology Squamous 85-90% Adenocarcinoma 10-15% Lymphoma Neuroendocrine/small cell Melanoma

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Route of Spread Cervical cancer spreads by direct invasion or by lymphatic spread Vascular spread is rare

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Staging Physical exam Cervical biopsies Chest x-ray IVP (Ct scan) Barium enema, cystoscopy, proctoscopy Surgical staging

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Staging Stage I – confined to the cervix IA1 – <3mm depth of invasion IA2 – stromal invasion 3-5mm in depth or <7 mm in width IB1- tumor < 4 cm IB2 - tumor > 4 cm in diameter Stage II – extension beyond cervix IIA – upper 2/3 of vagina IIB – Parametrial involvement

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Staging Stage III IIIA – lower 1/3 of vagina IIIB – extension to pelvic sidewall or hydronephrosis Stage IV IVA – bladder or rectal mucosa IVB – distant metastases

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5 year survival rates Stage IA 90-100% Stage IB 70-90% Stage II 50-60% Stage III 30-40% Stage IV 5%

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Therapy Cervical conization Simple hysterectomy Radical hysterectomy Radiation therapy with chemosensitization

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5 year Survival Stage I 70% Stage II 51% Stage III 33% Stage IV 17%

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Pros and Cons Surgery Bladder dysfunction Vesico/uretero fistula Bowel obstruction Ovarian preservation Vaginal preservation Radiation Sigmoiditis Rectovaginal fistula Bowel obstruction Vesico/uretero fistula Ovarian failure

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Radiation Therapy External Beam Whole pelvis or para-aortic window 4000-6000 cGy Over 4-5 weeks Brachytherapy Intracavitary or interstitial 2000-3000 cGy Over 2 implants

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Recurrent Cervical Cancer 10-20% of patients treated with radical hysterectomy Recurrence has an 85% mortality 83% are diagnosed within the first two years of post-treatment surveillance

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Recurrent Cervical Cancer Radiation Pelvic exenteration Palliative chemotherapy

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Vulvar Cancer 3870 new cases 2005 870 deaths Approximately 5% of Gynecologic Cancers American Cancer Society. Cancer Facts & Figures. 2004. Atlanta, GA; 2005

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Vulvar Cancer 85% Squamous Cell Carcinoma 5% Melanoma 2% Sarcoma 8% Others

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Vulvar Cancer Biphasic Distribution Average Age 70 years 20% in patients UNDER 40 and appears to be increasing

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Vulvar Cancer Etiology Chronic inflammatory conditions and vulvar dystrophies are implicated in older patients Syphilis and lymphogranuloma venereum and granuloma inguinal HPV in younger patients Tobacco

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Vulvar Cancer Paget’s Disease of Vulva 10% will be invasive 4-8% association with underlying Adenocarcinoma of the vulva

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Symptoms Most patients are treated for “other” conditions 12 month or greater time from symptoms to diagnosis

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Symptoms Pruritus Mass Pain Bleeding Ulceration Dysuria Discharge Groin Mass

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Symptoms May look like: Raised Erythematous Ulcerated Condylomatous Nodular

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Vulvar Cancer IF IT LOOKS ABNORMAL ON THE VULVA BIOPSY! BIOPSY! BIOPSY!

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Tumor Spread Very Specific nodal spread pattern Direct Spread Hematogenous

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Staging Based on TNM Surgical Staging Tumor size Node Status Metastatic Disease

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Staging Stage I T1 N0 M0 Tumor ≤ 2cm IA ≤1 mm depth of Invasion IB 1 mm or more depth of invasion

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Staging Stage II T2 N0 M0 Tumor >2 cm Confined to Vulva or Perineum

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Staging Stage III T3 N0 M0 T3 N1 M0 T1 N1 M0 T2 N1 M0 Tumor any size involving lower urethra, vagina, anus OR unilateral positive nodes

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Staging Stage IVA T1 N2 M0 T2 N2 M0 T3 N2 M0 T4 N any M0 Tumor invading upper urethra, bladder, rectum, pelvic bone or bilateral nodes

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Staging Stage IVB Any T Any N M1 Any distal mets including pelvic nodes

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Treatment Primarily Surgical Wide Local Excision Radical Excision Radical Vulvectomy with Inguinal Node Dissection Unilateral Bilateral Possible Node Mapping, still investigational

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Treatment Local advanced may be treated with Radiation plus Chemosensitizer Positive Nodal Status 1 or 2 microscopic nodes < 5mm can be observed 3 or more or >5mm post op radiation

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Treatment Special Tumor Verrucous Carcinoma Indolent tumor with local disease, rare mets UNLESS given radiation, becomes Highly malignant and aggressive Excision or Vulvectomy ONLY

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Vulva 5 year survival Stage I 90 Stage II 77 Stage III 51 Stage IV 18 Hacker and Berek, Practical Gynecologic Oncology 4th Edition, 2005

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Recurrence Local Recurrence in Vulva Reexcision or radiation and good prognosis if not in original site of tumor Poor prognosis if in original site

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Recurrence Distal or Metastatic Very poor prognosis, active agents include Cisplatin, mitomycin C, bleomycin, methotrexate and cyclophosphamide

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Melanoma 5% of Vulvar Cancers Not UV related Commonly periclitoral or labia minora

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Melanoma Microstaged by one of 3 criteria Clark’s Level Chung’s Level Breslow

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Melanoma Treatment Wide local or Wide Radical excision with bilateral groin dissection Interferon Alpha 2-b

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Vaginal Carcinoma 2140 new cases projected 2005 810 deaths projected 2005 Represents 2-3% of Pelvic Cancers American Cancer Society. Cancer Facts & Figures. 2004. Atlanta, GA; 2005

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Vaginal Cancer 84% of cancers in vaginal area are secondary Cervical Uterine Colorectal Ovary Vagina Fu YS, Pathology of the Uterine Cervix, Vagina and Vulva, 2nd ed. 2002

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Vaginal Carcinoma Squamous Cell 80-85% Clear Cell 10% Sarcoma 3-4% Melanoma 2-3%

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Clear Cell Carcinoma Associated with DES Exposure In Utero DES used as anti abortifcant from 1949-1971 500+ cases confirmed by DES Registry Usually occurred late teens

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Vaginal Cancer Etiology Mimics Cervical Carcinoma HPV 16 and 18

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Staging Stage I Confined to Vaginal Wall Stage II Subvaginal tissue but not to pelvic sidewall Stage III Extended to pelvic sidewall Stage IVA Bowel or Bladder Stage IVB Distant mets

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Treatment Surgery with Radical Hysterectomy and pelvic lymph dissection in selected stage I tumors high in Vagina All others treated with radiation with chemosensitization