University of Kentucky. Markey Cancer Center

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University of Kentucky Markey Cancer Center

Invasive Cancer of the Vagina and Urethra Fred Ueland, MD

No matter what you accomplish in your life, the size of your funeral will still be determined by the weather

Vaginal Cancer 1-2% of all gynecological cancers Incidence 0.6/100,000 Occurs less commonly than metastatic disease to vagina 60% have had previous hysterectomy

Etiology 3-10% associated with VAIN High association with HPV 30% with prior CIN Consider Residual disease from other primary New primary Association with radio-oncogenicity oncogenicity

Symptoms Painless bleeding 5% with pain from advanced disease 5% completely asymptomatic 20% missed on speculum exam

Relationships Uterus and cervix Pelvic lymph nodes Bladder and rectum TD 5/5= 5500 cgy TD 50/5= 8500 cgy

Vaginal Cancer Location Upper ⅓ 40% Middle ⅓ 13 Lower ⅓ 31% Entire 30% Anterior 40% Posterior 30% Lateral 30%

Dissemination Local Lymphatic drainage Obturator, iliac, pelvic Inguinal Unpredictable Hematogenous Less common

Lymphatic Drainage Upper vagina Common or external iliac lymph nodes Middle vagina Iliac or femoral triangle Lower vagina Femoral triangle, inguinal nodes Unpredictable drainage. Any pelvic node can be involved by a vaginal cancer in any location

Incidence of Vaginal Cancer Age Dependent 300 250 200 150 100 No. Cancers 50 0 15-29 30-39 40-49 50-59 60-69 70-79 >80

Histology Squamous 85% Adenocarcinoma 6% Melanoma 3% Sarcoma 3% Miscellaneous 3%

Adenocarcinoma of Vagina Only 6% of all vaginal cancers Arise from Mullerian adenosis Endometriosis Gartner s ducts Treatment is same May be more chemosensitive

Vaginal Cancer Staging Stage I Stage II Stage III Stage IVa Limited to vaginal mucosa Subvaginal tissue Pelvic sidewall IVa Adjacent organs or direct extension beyond true pelvis Stage IVb Distant spread

Vaginal Cancer Treatment

Picric Acid Used to manufacture explosives High explosive < 30% water Flammable solid >30% water

Vagina + Cervix Stage I Stage IIa Stage IIb Stage IIIa,b Stage IV Vagina Only Stage I (upper) Stage I (lower) Stage II Stage III Stage IV Individualize RH, upper vag, lymphad RH, total vag, lymphad Exenteration if XRT failure Exenteration if XRT failure Individualize Surgery RH, lymphadenectomy plus upper vaginectomy Exenteration if XRT failure Exenteration if XRT failure Surgery 5000 cgy for (+) LNs 5000 cgy 6000 cgy Radiation 5000 cgy for (+) LNs Radiation 5000 cgy for (+) LNs 5000 cgy + brachy 5000 cgy + brachy 6000 cgy + brachy

Vaginal Brachytherapy

Vaginal Brachytherapy Lesion depth < 0.5cm Cylinder implant Lesion depth > 0.5cm Syed-Neblett interstitial applicator Iridium ( 192 I) Consider laparoscopic visualization and omental J-flap

Vaginal Brachytherapy Tandem and Ovoids Locally advanced disease with uterus in-situ Cervical involvement Dosimetry like cervical cancer

Vaginal Brachytherapy Needle applicator Iridium-192 Alluvial deposits, rare Half-life life of 73.83 days 192 I beta decays into platinum-192 Laparoscopy and omental J-flap may be required Syed-Neblet

Recurrence Similar to vulvar and cervical cancers Epidermoid 80% found clinically 80% in pelvis and within 2 years Exenterative surgery for pelvic recurrence 40% success Chemotherapy often ineffective

Vaginal Cancer Survival

Vaginal Cancer Five-Year Survival Author Patients I II III IV All Stages Eddy 91 84 70 45 35 28 50 Stock 95 100 67 53 0 15 46 Creasman 98 792 73 58 58 58 NA

Vaginal Cancer Stock et al Gyn Onc 56:45, 1995 80 70 60 50 40 30 20 10 0 Stage I Stage II Stage III Stage IV Local % 5 year

Vaginal Cancer Unusual Cell Types

Unusual Vaginal Cancers Adenocarcinoma Clear cell CA Verrucous Locally invasive, rarely metastatic Melanoma Problematic Sarcoma Sarcoma botryoides Leiomyosarcoma Endodermal sinus tumor

Clear Cell Adenocarcinoma Herbst and Scully, April 1970 Age 15-22 offspring of DES exposed mothers Polypoid tumor 60% upper vagina 40% involve cervix also DES exposure before 18 weeks in utero Teratogenic (adenosis)) not carcinogenic

Clear Cell Adenocarcinoma Radical surgery Ovarian preservation Adjuvant therapy VAC Pelvic radiotherapy Treatment

Clear Cell Cancer Survival 100 90 80 70 60 50 40 30 20 10 0 I 2a 2b 2 va 3 4 Stage 5 yr 10 yr

Melanoma of Vagina Surgical therapy is mainstay Location Distal 1/3 55% Anterior 45% Overall survival < 20% No proven adjuvant therapy

Sarcoma Botryoides Embryonal rhabdomyosarcoma Undifferentiated mesenchyme of vaginal lamina propria Grape-like masses Vaginal cancer in children Age 3-53 5 years Peak incidence age 3 years Cervical origin in teens Treatment Surgery + VAC + XRT Survival 85-90%

Endodermal Sinus Tumor Rare 50 case reports Peak age 10 months (usually under 1 year) αfp Non-dysgerminomatous germ cell tumor Treatment Chemotherapy and partial vaginectomy Survival 85-90%

Conclusions 1. Clinical staging system 2. Radiotherapy 3. Modest cure rates 4. Prevention

Urethral Cancer Rare

Urethral Cancer Rare < 1% (600 reported cases) Poor prognosis Radical cystourethrectomy in early disease Radiotherapy Consider inguinal lymphadenectomy or pelvic imaging (fusion PET/CT) If (+), pelvic XRT

Urethral Cancer

Risk Factors Age > 60 White female Chronic inflammation: UTI, STD HPV

Signs and Symptoms Hematuria, vaginal spotting Pain or voiding dysfunction Dyspareunia Palpable mass in urethra or vagina Inguinal adenopathy Recurrent UTI Urinary fistula

Histology Squamous- distal ⅔ 60% Transitional- proximal ⅓ 20% Adenocarcinoma 10% Submucosa of periurethral (Skene)) glands Other Sarcoma 8% Melanoma 2%

Lymphatic Drainage Distal urethra ⅓ Superficial and deep inguinal lymph nodes Proximal urethra ⅔ Pelvic lymph nodes

Treatment Surgery Local excision Radical cystourethrectomy and lymphadenectomy Radiation Preop ChemoRT Postoperative RT Chemotherapy Mtx,, Vinblastine, Adriamycin, Cisplatin Protocol