UniversityUniversity ooff KentuckyKentucky MarkeyMarkey CancerCancer CenterCenter InvasiveInvasive CaCanncercer ofof thethe VVaaginagina andand UUrrethraethra

FredFred UeUelland,and, MMDD “N“Noo mamattterter wwhhatat youyou acacccomplishomplish inin yyoourur lifelife,, tthhee sizesize ooff yyoourur ffuuneralneral willwill stistillll bebe determindetermineedd byby thethe wweeatheatherr”” VaginalVaginal CancerCancer

 11--2%2% ofof allall gynecologicalgynecological cancanccersers  IncidenceIncidence 0.6/100,0000.6/100,000  OccursOccurs llessess ccoommmmonlyonly thanthan mmeettastatastatiicc diseasedisease toto vaginavagina  60%60% havehave hadhad previousprevious hysterecthysterectoommyy EtiologyEtiology

 33--10%10% associatedassociated withwith VAVAIINN  HighHigh associationassociation wwithith HPVHPV – 30% with prior CIN  ConsiderConsider – Residual disease from other primary – New primary – Association with radio-oncogenicity SSyymptomsmptoms

 PainlessPainless bleedingbleeding  5%5% withwith painpain frfromom advancedadvanced diseadiseassee  5%5% ccoompmplleteetellyy aasymsymptptoommaticatic

…20%…20% mmissedissed onon speculspeculumum exexaamm

RelationshiRelationshippss

 Uterus and cervix  Pelvic lymph nodes  Bladder and rectum – TD 5/5= 5500 cGy – TD 50/5= 8500 cGy VaginalVaginal CancerCancer LocatioLocationn

UpperUpper ⅓⅓ 40%40% AnterioAnteriorr 40%40% MiddleMiddle ⅓⅓ 1313 PosteriorPosterior 30%30% LowerLower ⅓⅓ 31%31% LateLaterraall 30%30% EntirEntiree 30%30% DisseminatDisseminatiionon

 LocalLocal  LLyymphatmphatiicc drainadrainaggee – Obturator, iliac, pelvic – Inguinal – Unpredictable  HHemaematogenoustogenous – Less common

LymLympphatichatic DrainageDrainage

 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

IncidenceIncidence ofof VaginalVaginal CancerCancer AgeAge DependentDependent

300

250

200

150 No. Cancers 100

50

0 15-29 30-39 40-49 50-59 60-69 70-79 >80 HistologyHistology

 SquSquaamoumouss 85%85%  AdenocarcinAdenocarcinomaoma 6%6%  MelanMelanomomaa 3%3%  SarcSarcomomaa 3%3%  MisMisccellaneousellaneous 3%3% AdenocarcinomaAdenocarcinoma ofof VVaaginagina

 OnlyOnly 6%6% ofof allall vavagginalinal cancanccersers  AriseArise frfromom – Mullerian adenosis – Endometriosis – Gartner’s ducts  TreaTreattmmentent iiss ssaammee  MMaayy bbee mmororee chchememoossensitiveensitive VaginalVaginal CancerCancer StagingStaging

 Stage I LLimimitedited toto vaginalvaginal mumucosacosa  Stage II SubvaginalSubvaginal tissuetissue  Stage III PelvicPelvic sidesidewwallall  Stage IVa AdjacentAdjacent organsorgans oorr directdirect extensionextension beyondbeyond truetrue pelvispelvis  Stage IVb DistantDistant sprspreeadad VaginalVaginal CancerCancer

…TreatmentTreatment PicricPicric AcidAcid

 Used to manufacture explosives  High explosive – < 30% water  Flammable solid – >30% water

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

 LesionLesion depthdepth << 0.50.5cmcm – Cylinder implant  LesionLesion depthdepth >> 0.50.5cmcm – Syed-Neblett interstitial applicator – Iridium (192I) – Consider laparoscopic visualization and omental J-flap VaginalVaginal BrachytherapyBrachytherapy TandemTandem andand OvoidsOvoids

 Locally advanced disease with uterus in-situ  Cervical involvement  Dosimetry like cervical cancer VaginalVaginal BrachytherapyBrachytherapy SSyedyed--NebletNeblet

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

RecurrenceRecurrence

 SSimimilailarr toto vulvarvulvar aandnd cervicalcervical cancanccererss – Epidermoid  80%80% ffooundund clinicallyclinically  80%80% inin pelvispelvis andand withinwithin 22 yeyeaarsrs  ExenterativeExenterative surgsurgeeryry forfor pelvicpelvic rrecurecurrrenceence – 40% success  ChCheemothmotheeraprapyy oftenoften ineffectiveineffective VaginalVaginal CancerCancer

…SurvivalSurvival VaginalVaginal CancerCancer FiveFive--YearYear SurvivalSurvival

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 792 73 58 58 58 NA ‘98 VaginalVaginal CancerCancer Stock et al Gyn Onc 56:45, 1995

80 70 60 50 40 Local % 30 5 year 20 10 0 Stage I Stage II Stage III Stage IV VaginalVaginal CancerCancer

…UnusualUnusual CellCell TTyypespes UnusualUnusual VaginalVaginal CancersCancers

 Adenocarcinoma – Clear cell CA  Verrucous – Locally invasive, rarely metastatic  Melanoma – Problematic  Sarcoma – Sarcoma botryoides – Leiomyosarcoma  Endodermal sinus tumor ClearClear CellCell AdenocarcinAdenocarcinoomama

 HerbstHerbst andand SculScullly,y, AprilApril 19701970  AgeAge 1515--2222 oofffsprifsprinngg ofof DESDES exposedexposed mmothotheersrs  PolypoidPolypoid ttuumormor – 60% upper vagina – 40% involve cervix also  DESDES exposureexposure beforebefore 1818 weekweekss inin uteroutero  TeratogenicTeratogenic ((adeadennosisosis)) notnot carcinogcarcinogeenicnic ClearClear CellCell AdenocarcinAdenocarcinoomama TreatmentTreatment

 RadicalRadical surgesurgerryy – Ovarian preservation  AdjuvantAdjuvant therapytherapy – VAC – Pelvic radiotherapy ClearClear CellCell CancerCancer SurvivalSurvival

100 90 80 70 60 50 5 yr 40 10 yr 30 20 10 0 I 2a 2b 2 va 3 4 Stage MelanomaMelanoma ooff VaginaVagina

 SurgicalSurgical theratherappyy iiss mmainstainstaayy  LocationLocation – Distal 1/3 55% – Anterior 45%  OverallOverall survivalsurvival << 20%20%  NoNo provenproven adjuvaadjuvanntt therapytherapy SarcomaSarcoma BBootryoidestryoides

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

 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% ConclusionConclusionss

1. ClinicalClinical stagingstaging ssyyststemem 2. RadiotherapyRadiotherapy 3. ModestModest cucurree rratesates 4. PreventionPrevention

UrethralUrethral CCaancerncer

…RareRare UrethralUrethral CCaancerncer

 RareRare – < 1% (600 reported cases)  PoorPoor prognosiprognosiss  RadicalRadical cystouretcystourethhrectrectomyomy inin earearllyy ddiiseasesease  RadiotherapyRadiotherapy  ConsiderConsider inguinalinguinal llymymphadenectphadenectoomymy oror pelvicpelvic imimagingaging (fusion(fusion PET/CT)PET/CT) – If (+), pelvic XRT UrethralUrethral CCaancerncer RiskRisk FactorFactorss

 AgeAge >> 6060  WhiteWhite ffeemmaleale  ChronicChronic inflinflaammmmaattion:ion: UTI,UTI, SSTTDD  HPVHPV SignsSigns andand SSymptymptoomsms

 HHemaematuriaturia,, vaginalvaginal spottingspotting  PainPain oror voidingvoiding dysfunctidysfunctioonn  DyspaDysparreuniaeunia  PalpablePalpable mamassss inin uurethrarethra oorr vaginavagina  InguinalInguinal adenopaadenopatthyhy  RecurrentRecurrent UTIUTI  UrinaUrinarryy fistulafistula HistologyHistology

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

 DistalDistal urethurethrraa ⅓⅓ – Superficial and deep inguinal lymph nodes  ProxProximimalal urethrurethraa ⅔⅔ – Pelvic lymph nodes TreatmentTreatment

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