Jane L. Meisel and William P. Tew
VULVAR CANCER
Epidemiology
• 4th most common gynecologic CA
• Estimated 4490 new cases dx’d & 950 death in the United States in 2012 (American Cancer Society, Cancer Facts and Figures, 2013)
• Occurs most frequently in postmenopausal women (mean age at dx 65) but age at dx is ↓, possibly due to ↑ HPV-related CA in younger women (women <45 y w/vulvar CA more likely to have associated condyloma, p < 0.001) (Obstet Gynecol 1995;86(1):51)
• RF: Tobacco use, vulvar dystrophy, vulvar or CIN, HPV infxn, immunodeficiency syndromes, prior cervical CA
Clinical Manifestations & Diagnosis
• Unifocal plaque, ulcer, or mass on labia majora; in 10%, lesion too extensive to determine site of origin; in up to 22%, synchronous second malignancy (most often cervical), is found (Am J Obstet Gynecol1971;109:446).
• Vulvar bleeding, dysuria, groin LAN suggest advanced disease
• Dx: Made by vulvar bx; also do Pap & colposcopy to r/o synchronous vaginal/cervical lesions; if tumor ≥2 cm or mets suspected, CT A/P
Histologic Subtypes
• Squamous cell carcinoma (over 90% of 1° vulvar neoplasms)
-Keratinizing/differentiated/simplex → most common: Older pts, assoc w/lichen sclerosus & chronic venereal granulomatous disease
-Classic/warty/Bowenoid type → younger pts, assoc w/HPV 16, 18, & 33, early age at first intercourse, multiple sexual partners, HIV, smoking
-Verrucous carcinoma: SCC variant; grows slowly, rare nodal mets but can be locally destructive
• Melanoma (5–10%): Usu pigmented but can be amelanotic
• BCC (2%): Postmenopausal Caucasians, locally invasive (usu nonmetastasizing); high incidence of add’l antecedent/concomitant malignancy
• Sarcoma (1–2%): Poor prognosis
• Extramammary Paget disease (<1%): Older Caucasians; pruritis in 70%; eczematoid appearance. Evaluate for synchronous neoplasms (20–30%)
• Bartholin gland adenoCA (<1%): Solid, deeply infiltrating, often metastasize
Staging
• Staging & 1° surgical tx performed simultaneously; inguinofemoral lymph node status most important predictor of overall prognosis (70–93% 5YS if negative, 25–41% if positive (Crit Rev Oncol Hematol2006;60:227))
Treatment
• Stage I/II: Surgery-most conservative procedure resulting in ≥1 cm tumor-free margin (margins ≤ 8 mm minimize local recurrence, Gynecol Oncol 2007;104:636)
Options = radical local excision, partial vulvectomy, radical vulvectomy; inguinofemoral LN dissection in all except IA (Gynecol Oncol 1994;53:55)
If margins <1 cm after excision, re-excision preferable to RT; adjuvant RT may benefit high-risk node-neg pts (tumor > 4.1 cm, + margins, LVI)
• Stage III/IV: Surgery for most pts, w/post-op ipsilateral groin & pelvic RT in (a) stage IVA disease, (b) + margins, (c) ≥ 2 microscopically + LN, (d) ≥ 1 macroscopically +LN, or (e) evidence of extracapsular spread. Post-op RT significantly ↓ local relapses & CA-related death in node-positive pts (Obstet Gynecol 2009;114:537).
If disease fixed to bone or pt requires ostomy due to bowel/bladder involvement, tx w/CIS + RT, w/local excision for residual disease
• Recurrent disease: >50% recurrences are perineal & tx = re-excision; inguinal/pelvic recurrence tx = RT + surgery; distant recurrence = salvage chemo
• Met disease: 5FU + CIS
• Vulvar melanoma: Excision for locoregional disease; little data in met disease but principles of tx of cutaneous melanoma can be employed (vemurafenib, anti-CTLA-4 Rx, CIS-based chemo-tx)
VAGINAL CANCER
Epidemiology
• Occurs in 1/100000 women; up to half may have hx of prior GYN malignancy (Gynecol Oncol 1995;56(3):435)
• RF: HPV, high no. of sexual partners, smoking, intercourse at early age
Clinical Presentation & Diagnosis
• Sx: Postcoital or postmenopausal vaginal bleeding; bloody vaginal discharge, vaginal mass, urinary frequency or dysuria, tenesmus, constipation, melena. Pelvic pain (if disease extends beyond vagina). 20% asx at time of dx.
• Posterior wall of upper 1/3 of vagina = most common site
• Dx: Mass, plaque, or ulcer on exam; + Pap or colpo; definitive test = vaginal bx
Histologic Subtypes
• Squamous cell carcinoma (∼84%): Incidence ↑ w/age (mean age at dx = 60 y); can be nodular, ulcerative, indurated, endophytic, or exophytic. Assoc w/HPV. Verrucous carcinoma → rare, well differentiated; locally aggressive but mets rare
• AdenoCA (∼10%): Nearly all vaginal CA in pts <20 y are adenocarcinomas; clear-cell variant assoc w/DES exposure in utero. Polypoid masses often on ant. vaginal wall; 70% stage I at dx; improved outcome compared to non–DES-assoc. vaginal adenoCA; median age at dx = 19 y)
• Sarcoma (∼3%): Most vaginal sarcomas are embryonal rhabdomyosarcomas (sarcoma botryoides). Mostly young children (mean age 3 y), “bunch of grapes”
• Melanoma (∼3%): Mean age 60, presents w/vaginal bleed & blue-black/black-brown mass, plaque, or ulceration of distal 1/3 ant. vaginal wall. 5-y OS <20%
Staging
• Staging is clinical (incorporates pelvic exam, cystoscopy, radiology results as well as any pathologic info from bx or resection)
• Stage I = confined to vagina, II =invades paravaginal tissues but not to pelvic wall, III = extends to pelvic wall, or not to pelvic wall but accompanied by pelvic or inguinal lymph node mets, IVA = invades bladder or rectum &/or extends beyond pelvis, IVB = any tumor size or nodal distribution w/evidence of distant mets
• At dx, ∼ ¹¼ pts w/stage I & III disease, ∼1/3 stage II, ∼12% stage IV
Tx & Prognosis
• Stage I—surgery (radical hysterectomy, upper vaginectomy, b/l pelvic lymphadenectomy) or XRT (brachytx if <2 cm, EBRT ± brachytx if >2 cm) for lesions in upper vagina; XRT for lesions in mid-lower vagina
• Stage II—one studied approach: Neoadj paclitaxel/CIS + radical surgery or + XRT (Gynecol Oncol 2008;111:307)
Complications of tx (10–15%): Rectovaginal, vesicovaginal fistulas; radiation cystitis, proctitis; rectal/vaginal strictures; rarely, vaginal necrosis, radiation-induced premature menopause (esp if <40 y)
• Stage III/IV—poor prognosis w/XRT alone; 5-FU or CIS often used concurrently w/XRT; pelvic exenteration a consideration in stage IVa disease
• Recurrent disease—pelvic exenteration w/or w/o vaginal reconstruction
• 5-y OS: 77.6% stage I, 52.2% stage II, 42.5% stage III, 20.5% stage IVA, 12.9% stage IVB (Int J Gynaecol Obstet 2006;95:S29)