RadiationTherapyforTesticularCancer

StevenW.Davis,MD

Case

• 41y.o.malepresentswitha6weekhistoryofpainfulrighttesticle

• Othersx’s:decreasedlibido• PMHx:Eczema,seasonalallergies• PSHx:Vasectomy• Medications:Rhinocort• Allergies:NKDA

Case

• FamilyHx:Nohistoryofcancer• SocialHx:Marriedwith3children• ROS:negative• Exam:scrotumwithoutlesion,TTPofrighttesticlebutnopalpablemass

• Labs:serumAFP,LDH,andHCG:WNL

Case

• UltrasoundScrotum:–Multiplenodulesinrighttesticle– Givenmultifocality,mayrepresentnon-seminomatous tumor

– Righthydrocele• CT:Abdomen/Pelvis– Noevidenceofmetastaticdisease

• CXR:– Noevidenceofdisease

Case

• Rightradicalorchiectomy• Pathology– Testicle,right,radicalorchiectomy:• Spermatocytic seminoma• Multifocal,1.0,0.5cm• Limitedtotestes,marginsnegative,noLVI• pT1NXS0,StageIA• IHC:-OCT3/4

• Referredtoradiationoncologyforevaluationforadjuvanttherapy

http://upload.wikimedia.org/wikipedia/commons/e/ef/Spermatocytic_seminoma_intermed_mag.jpg

http://www.webpathology.com/slides/slides/Testes_SpermatocyticSeminoma14.jpg

TesticularCancer• Only1-2%ofmalignant

tumorsinmen• Mostcommonmalignant

tumorinmenages15-35• World(2008):52,000cases

with9000deaths• US:8480caseswith350

deaths

• Isochrome 12pin80%ofgermcelltumors– DDX1,KRAS,c-KIT(ligand KITGL)– ITGCNandinvasivetumors

ClassificationofTesticularTumors

• GermCellTumors(95%)– Seminomatous (35%)• Seminoma• Spermatocytic Seminoma

– Non-seminomatous (5-10%)• Embryonal• YolkSac• Choriocarcinoma• Teratoma

–Mixed(50-60%)

ClassificationofTesticularTumors

• SexCordStromal Tumors– Leydig CellTumors– Sertoli CellTumors

• Others– Lymphoma(mostcommoninage>65)– Sarcomas

GermCellTumors• 10%occuroutsideofTestes– Mostcommonlocations:retroperitoneum andanteriormediastinum

– Dysgerminoma ofOvary/mediastinum

• Seminomas:4th Decade• Non-seminomas:3rd Decade

• EuropeanDecent:6.36/100,000• AfricanDecent:1.30/100,000

Seminoma

• Mostcommonsingletumortype(35%)• 85%presentinstageI• RiskFactors– Cryptorchidism– Klinefelter’s Syndrome– Diethylstibestrol (DES)exposure– Immunosuppression

Spermatocytic Seminoma

• Olderage50-60• Rarelymetastasize(1of>200casesinliterature)

• Morelikelybilateral:8-10%vs 2-4%• Treatment:–Mosturologistsrecommendorchiectomy withsurveillance

– Nogreatdataavailable

http://www.webpathology.com/slides/slides/Testes_GCT_ITGCN3.jpg

http://www.imagingpathways.health.wa.gov.au/includes/images/a_scrot/seminoma_he.jpg

http://upload.wikimedia.org/wikipedia/commons/c/c5/Embryonal_carcinoma_-_high_mag.jpg

http://www.humpath.com/IMG/jpg/yolk_sac_tumor_4.jpg

http://www.surgicalpathologyatlas.com/glfusion/mediagallery/media.php?f=0&sort=0&s=200904231211429

http://www.uaz.edu.mx/histo/pathology/ed/ch_18/c18_dermoid.jpg

StageTNMsystem GroupingTXUnknownstatusoftestis Stage0– Tis,N0,M0,S0T0Noapparentprimary(includesscars) StageIA– T1,N0,M0,S0Tis Intratubular tumor,noinvasion StageIB– T2-T4,N0,M0,S0T1Testisandepididymis only;novascularinvasionor StageIS– anyT,N0,M0,S1-S3penetrationoftunicaalbuginea StageIIA– anyT,N1,M0,S0-S1T2Testisandepididymis withvascularinvasionorthrough StageIIB– anyT,N2,M0,S0-S1tunicaalbuginea toinvolvetunicavaginalis StageIIC– anyT,N3,M0,S0-S1T3Spermaticcord StageIIIA– anyT,anyN,M1a,S0-S1T4Scrotum StageIIIB– anyT,anyN,M0-M1a,S2

StageIIIC– anyT,anyN,M0-M1a,S3anyT,anyN,M1b,anyS

N0NoregionalnodeinvolvementN1Nodemassorsinglenodes≤2cm;≤5nodesinvolved;nonode>2cmN2Nodemass>2but≤5cm;or>5nodesinvolved,none>5cm;orextranodal tumorN3Nodemass>5cm

MXUnknownstatusofdistantmetastasesM0NodistantmetastasesM1aNon-regionalnodalorlungmetastasesM1bDistantmetastasisotherthannon-regionalnodalorlungSXNomarkerstudiesavailableS0Allmarkerstudiesnormal

LDH[*] hCG (mIU/mL) AFP(ng/mL)S1 <1.5× N& <5000& <1000S2 1.5–10× Nor 5000–50000or 1000–10000S3 >10× Nor >50000or >10000

*LDHlevelsexpressedaselevationsaboveupperlimitofnormal(N).

SerumTumorMarkers• HCG– Elevatedinchoriocarcinoma– 15%ofseminoma patients

• AFP– Elevatedinyolksactumor– Ifelevated,notpureseminoma

• LDH– Elevatedin60%ofGCT– Acutephasereactant

• Measurementbefore/afterorchiectomy canhelpmonitortreatmentresponse,diseaseremission

Survival

• Seminomas 5-yrOS– StageI:virtually100%– StageII:97%– StageIII:85%

• Non-seminomatous GermCellTumors5-yrOS– StageI:99%– StageII:98%– StageIII:86-50%

StageIIIRiskStratification

TreatmentDecisions

• Surgery:Radicalinguinalorchiectomy withhighligationofspermaticcord– Onlydeferredforhigh-burdenmetastaticdiseasewhenchemotherapymaybeofferedfirst

• Seminoma vs.NSGCT/MixedTumor

• StageatPresentation– StageI,StageIIorStageIII

NSGCTStageI

• Surveillance– 21%recurrencerate– Usuallyinfirst12months(after24monthsrare)– UsuallytoretroperitonealLNs(60%)– Chemotherapyforsalvage:>98%cure

• RPLNDwithnervesparing– 10%recurrencerate

• SinglecycleadjuvantBEP– Cisplatin,Etoposide,Bleomycin

• 1996-2005:286patientsrandomizedtoRPLNDor1CycleofBEP• Relapserateof10%vs 3%recurrence(HR7.9at24months)

NSGCTStageIIandIII

• StageII– IIA– observationvs.RPLNDvs.2cyclesofBEP• Teratoma mayfavorsurgery

– IIB/C– chemotherapyBEPx2• StageIII– ChemotherapyBEPx3- 4– Goodprognosis5-yrOS80%,Poor50%– Increasedsurvivalatspecialtycenters

Seminoma StageI

• Historicallypatientsgotradiation:– 30Gy/15fractionsin“dogleg”configuration-paraaortics withipsilateral inguinals

– MRCtrialTE10,1999,PAvs.“dogleg”• Fields:PA(supT10/T11,inf L5/S1,latinclusionofipsilateral renalhilum);Dog-Leg(supT10/T11;

inf mid-obturator foramen;ipsilateral inclusionofrenalhilum verticallydowntoL5/S1,thendiagonaltolateraledgeofacetabulum,thenverticallydowntomid-obturator foramen;contralateral transverseprocessverticallytoL5/S1,thendiagonalparallelwithipsilateral andverticallydowntomid-obturator foramen)

• 478Men,samerelapserate,lowertoxicityandbetterspermcountswithPA

– MRCtrialTE18,2005,30Gy/15vs 20Gy/10• 628men,samerelapserate• returntoworksooner(relativelysimilartoxicityat12wks,lesslethargyat4weeks)

MRCtrialTE19/EORTC30982

• 1447patientsin14countries– 1cyclecarboplatin vs.radiationtherapy(30/15or20/10)

– 2005• 3-yrRFScarbo 95%vs RT96%• Toxicity:reportedlessfatiguewithcarbo• Decreased2nd testiculartumorswithcarbo 10vs 2

– 2011• 5-yrRFScarbo 94.7%vs RT96%• Contralateral GCTcarbo 2RT15HR0.22,P=0.03

RiskofSecondaryMalignancy

• 2005,Scandanavian Study• >40,000testiculartumors• Showedlifetimeriskof36%vs 23%forsolidvisceralcancers– Stomach,Bowel,Pancreas,andLiver

• 10patients• Plannedwithprotonsandtraditionalphotons• Predicted6.94excessbladder,largebowel,pancreasandstomachcancerswithphotons

Seminoma StageIIA/IIB

• EBRT– 20Gy/10fractionstoparaaortics andpelviclymphnodes

• Boostdose(+10Gy forIIAand+16Gy forIIB)forgrosslymphnodedisease

• Prioringuinalsurgerydisruptslymphatics andmayrequirecontralateral nodecoverage

Seminoma IICandIII

• Chemotherapy– EPx4vs BEPx3(BEPx4forintermediates)– EithergoodorintermediateIGCCCGprognosticgroup

Case

• Chosesurveillance• Follow-up– Followupvisit,CTabdomenandpelvisandLabs• every3-4monthsx3years• thenq6monthsx4years• Thenq1yearuntil10years

References• PeterW.M.Chunga,AndrewJ.S.Bayleya,JoanSweetb,MichaelA.S.Jewettc,BettyTew-Georgea,MaryK.Gospodarowicza,

Padraig R.Wardea,*Spermatocytic Seminoma:AReviewEuropean Urology45(2004)495–498• RandomizedphaseIIItrialcomparingretroperitoneallymphnodedissectionwithonecourseofbleomycin andetoposide

pluscisplatin chemotherapyintheadjuvanttreatmentofclinicalstageINonseminomatous testiculargermcelltumors:AUOtrialAH01/94bytheGermanTesticularCancerStudyGroup.AlbersP,Siener R,Krege S,Schmelz HU,Dieckmann KP,Heidenreich A,Kwasny P,Pechoel M,LehmannJ,Kliesch S,Köhrmann KU,Fimmers R,Weissbach L,LoyV,Wittekind C,HartmannM;GermanTesticularCancerStudyGroup.DepartmentofUrology,Klinikum KasselGmbH,Kassel,Germany.sekurol@uni-duesseldorf.JClin Oncol.2010Mar10;28(8):1439.

• GundersonandTepper.ClinicalRadiationoncology.2011.ElsevierandSanders• Hansen,EKandRoachM.HandbookofEvidence-BasedRadiationOncology.2nd edition.2011SpringerPress