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Cervical/Vulvar/Vaginal Cancer

Cervical/Vulvar/Vaginal Cancer. Steve Remmenga, M.D. The McClure L Smith Professor of Gynecologic Oncology Division of Gynecologic Oncology Department of OB/GYN University of Nebraska Medical Center. Cervical Cancer. Estimated incidence and mortality in the United States (2007)¹

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Cervical/Vulvar/Vaginal Cancer

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  1. Cervical/Vulvar/Vaginal Cancer Steve Remmenga, M.D. The McClure L Smith Professor of Gynecologic Oncology Division of Gynecologic Oncology Department of OB/GYN University of Nebraska Medical Center

  2. Cervical Cancer • Estimated incidence and mortality in the United States (2007)¹ • 11,150 new cases • 3,670 deaths • 1:168 Lifetime risk 1. American Cancer Society. Cancer Facts & Figures. 2007. Atlanta, GA; 2007

  3. Cervical Cancer • <2% of all cancer deaths in women (twice as deadly in African-American women) • 5-year survival: 71% 1. American Cancer Society. Cancer Facts & Figures. 2004. Atlanta, GA; 2005

  4. Cervical CA • International estimates • Approximately 570,000 cases expected worldwide each year • 275,000 deaths • Number one cancer killer of women worldwide

  5. Pap Smear • With the advent of the Pap smear, the incidence of cervical cancer has dramatically declined

  6. Cervical Cancer

  7. Cervical CA Etiology • Cervical cancer is a sexually transmitted disease. • HPV DNA is present in virtually all cases of cervical cancer and precursors. • Some strains of HPV have a predilection to the genital tract and transmission is usually through sexual contact (16, 18 High Risk). • Little understanding of why small subset of women are affected by HPV. • HPV may be latent for many years before inducing cervical neoplasia.

  8. 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

  9. Prevention • Educate all providers, men and women regarding HPV and the link to cervical cancer. • Adolescents are an especially high-risk group due to behavior and cervical biology. • Delay onset of sexual intercourse. • Condoms may help prevent sexually transmitted disease.

  10. 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

  11. 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.

  12. Symptoms of Invasion • May be silent until advanced disease develops • Post-coital bleeding • Foul vaginal discharge • Abnormal bleeding • Pelvic pain • Unilateral leg swelling or pain • Pelvic mass • Gross cervical lesion

  13. Cell Type • Squamous Cell Carcinoma 80-85% • AdenoCarcinoma 15% • Adenosquamous • Others

  14. Staging • Clinical Staged Disease • Physical Exam • Blood Work • Cystoscopy • Proctoscopy • IVP

  15. Staging Cervical Cancer • Stage I Confined to Cervix • Ia1 <3 mm deep, < 7 mm wide • Ia2 >3 <5 mm deep, • Ib1 < 4cm • Ib2 > 4 cm

  16. Microscopic Disease • Squamous carcinoma of the cervix that has <3mm invasion from the basement membrane • The diagnosis must be based on a cone or hysterectomy specimen. • No lymph-vascular invasion • May be successfully treated with fertility preservation in selected patients • These patients should all be referred for consultation.

  17. Staging • Stage II Upper 2/3 vagina or Parametrial involvement • IIA Upper 2/3 vagina with no Parametrial • IIB Parametrial Involvement

  18. Staging • Stage III Lower 1/3 Vagina, Sidewall or ureteral involvement • IIIA Lower 1/3 of Vagina • IIIB Sidewall or Ureteral Involvement

  19. Staging • Stage IV Bladder, Rectal or Distal Spread • IVA Bladder or Rectal Involvement • IVB Distal Spread

  20. Treatment of Early Disease • Conization or simple hysterectomy (removal of the uterus) - microinvasive cancer • Radical hysterectomy - removal of the uterus with its associated connective tissues, the upper vagina, and pelvic lymph nodes. Ovarian preservation is possible. • Chemoradiation therapy

  21. Advanced Disease • Chemoradiation is the mainstay of treatment • 4-5 weeks of external radiation • Two or more implants (brachytherapy) • Concurrent Cisplatin-based chemotherapy significantly improves the chances of survival • Radiation treats the primary tumor and adjacent tissues and lymph nodes • Chemotherapy acts as a radiation sensitizer and may also control distant disease

  22. What is Standard Therapy for Stage IB2 - IVA Cervical Carcinoma? • External beam pelvic radiation (4,000 to 6,000 cGy) • Brachytherapy (8,000 to 8,500 cGy to Point A) • I.V. Cisplatin chemotherapy • Cisplatin 40mg/m2 (Max dose 70mg) IV q wk during RT (6wks) GOG 120-NEJM 340(15):1144, 1999

  23. Symptoms of Recurrence • Weight loss, fatigue and anorexia • Abnormal vaginal bleeding • Pelvic pain • Unilateral leg swelling or pain • Foul discharge • Signs of distant metastases • NOTE: must distinguish radiation side effects from recurrent cancer

  24. Management of Recurrence • Chemoradiation may be curative or palliative, especially in women who have not received prior radiation therapy. • Isolated soft tissue recurrence may occasionally be treated by resection with long-term survival.

  25. Recurrent Cervical Cancer: GOG 169 Moore DH et al. J Clin Oncol 22:3113-3119. 2004

  26. Topotecan in Recurrent Cervical Cancer – Overview of Phase II Studies Reference Regimen Evaluable Prior CT ORR Median OS (n) Single Agent (dailyx5): Bookman 1.5mg/m2/d 40 85% 13% 6.6 mo Muderspach 1.5mg/m2/d 43 None 19% 6.4 mo Noda 1.2mg/m2/d 22 82% 18% NR Combinations: Fiorica Topo + cisplatin 32 None 28% 10 mo Tiersten Topo + paclitaxel 13 33% 54% 8.6 mo • Bookman MA et al. Gynecol Oncol 2000; 77: 446-449. . Muderspach LI, et al., Gynecologic Oncology 2001;81: 213-215. Noda K, et al. Proc Am Soc Clin Oncol 1996;15:280 [Abstract 754]. Fiorica J, et al. Gynecol Oncol 2002;85:89-94. Tiersten AD, et al. Gyn Oncol 2004;92:635-638

  27. Recurrent Cervical Cancer:GOG 179 Regimen I Cisplatin 50 mg/m² Cervix Cancer Stage IV B or Regimen II Recurrent Topotecan 0.75 g/m²/d1-3 Cisplatin 50 mg/m² d 1 R A N D O M I Z E Long HJ, et al. Gynecol Oncol 2004; 92:397(SGO)

  28. SurvivalBy Treatment Group 1.0 Rx Group Alive Dead Total Cisplatin 17 129 146 Cis+Topo 29 118 147 0.9 0.8 0.7 Proportion Surviving 0.6 0.5 0.4 0.3 0.2 0.0 0.1 Months on Study 0 12 24 36 GOG 179

  29. GOG Protocol 179 Response rates based on previous cisplatin therapy (with RT) No Prior PlatinumPrior Platinum CDDP arm 20% 8% CDDP/Topo arm 39% 15%

  30. Comparing GOG 169 to 179 • Studies from two different eras • 169 before Chemo-RT • 179 during transition to Chemo-RT • Both showed no QoL disturbance with more aggressive regimens • In the new era chemo/RT • Response rate to CDDP less • Survival after single agent CDDP less • Survival advantage when add Topotecan • Survival Advantage when add Paclitaxel?

  31. Survival

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

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

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

  35. 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

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

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

  38. Symptoms • Pruritus • Mass • Pain • Bleeding • Ulceration • Dysuria • Discharge • Groin Mass

  39. Symptoms • May look like: • Raised • Erythematous • Ulcerated • Condylomatous • Nodular

  40. Vulvar Cancer • IF IT LOOKS ABNORMAL ON THE VULVA • BIOPSY! • BIOPSY! • BIOPSY!

  41. Tumor Spread • Very Specific nodal spread pattern • Direct Spread • Hematogenous

  42. Staging • Based on TNM Surgical Staging • Tumor size • Node Status • Metastatic Disease

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

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

  45. 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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