Management of Early stage Management of Early stage Malignant Ovarian Germ Cell TumoursMalignant Ovarian Germ Cell Tumours
Michael J Seckl
Charing Cross Hospital Campus of Imperial College NHS Healthcare TrustImperial College London, UK
9-129-12thth June 2010 Caravaggio Meeting on Rare Gynae June 2010 Caravaggio Meeting on Rare Gynae CancersCancers
What are OGCTs? - PathologyWhat are OGCTs? - Pathology
• DysgerminomasDysgerminomas
• Anaplastic GCTs/ Malig teratomas Anaplastic GCTs/ Malig teratomas embryonal Ca (undifferentiated)embryonal Ca (undifferentiated)polyembryoma (embryoid bodies)polyembryoma (embryoid bodies)endodermal sinus/yolk sacendodermal sinus/yolk sachepatoidhepatoidchoriocarcinomachoriocarcinoma
• Immature grade II/IIIImmature grade II/III
• MixedMixed
Pre-malignantPre-malignant MalignantMalignant• TeratomasTeratomas
immature (grade I)immature (grade I)mature (cystic)mature (cystic)monodermal teratomasmonodermal teratomas
Clinical presentationClinical presentation
• Abdominal distension, obstructionAbdominal distension, obstruction
• Rapid growth: haemoperitoneum/acute abdomenRapid growth: haemoperitoneum/acute abdomen
• hCG suppressed menstruation/ breast tendernesshCG suppressed menstruation/ breast tenderness
• Dysgerminomas: rare hypercalcaemiaDysgerminomas: rare hypercalcaemia
• Elevated hCG or AFP (CA125 and LDH)Elevated hCG or AFP (CA125 and LDH)
InvestigationsInvestigations
• U/S Doppler pelvisU/S Doppler pelvis
• CT chest/abdo/pelvisCT chest/abdo/pelvis
• MRI pelvisMRI pelvis
• Tumour markers (hCG, AFP, CA125, LDH)Tumour markers (hCG, AFP, CA125, LDH)
• If lung mets then MRI brainIf lung mets then MRI brain
• 1818FDG-PET?FDG-PET?
• Genetics?Genetics?
SurgerySurgery
• Unilateral salpingoophrectomy Unilateral salpingoophrectomy
• Biopsy omentum Biopsy omentum
• Biopsy contralateral ovary?Biopsy contralateral ovary?
• Locoregional LN samplingLocoregional LN sampling
• Peritoneal washingsPeritoneal washings
Surgical issues: a cancer perspectiveSurgical issues: a cancer perspective
• Laparoscopy vs laparotomy?Laparoscopy vs laparotomy?
• less invasive butless invasive but
• large tumours require morcellationlarge tumours require morcellation
• Morcellation in-situ may convert to IcMorcellation in-situ may convert to Ic
• Port-site metastasis??Port-site metastasis??
• Ease of staging??Ease of staging??
Surgical issues: LN staging importance?Surgical issues: LN staging importance?
Kumar et al et al Gynecol Oncol 2008Kumar et al et al Gynecol Oncol 2008
Stage IA management choicesStage IA management choices
• Surveillance?Surveillance?
• Adjuvant chemotherapy?Adjuvant chemotherapy?
• Adjuvant radiotherapy for dysgerminomas?Adjuvant radiotherapy for dysgerminomas?
• Surgery?Surgery?
CXH Stage Ia SurveillanceCXH Stage Ia Surveillance3-6 wks post-op: 3-6 wks post-op: CT chest/abdo/pelvis, MRI + Doppler U/S pelvisCT chest/abdo/pelvis, MRI + Doppler U/S pelvis
3 months (m):3 months (m): CT chest/abdo, MRI + Doppler U/S pelvisCT chest/abdo, MRI + Doppler U/S pelvisNormal then laparoscopyNormal then laparoscopy
6 - 48 m (6 mthly):6 - 48 m (6 mthly): MRI + U/S pelvis and abdomenMRI + U/S pelvis and abdomen
12 m:12 m: CT chest/abdoCT chest/abdo
24 m:24 m: CT chest/abdo (dysgerminomas only)CT chest/abdo (dysgerminomas only)
11stst yr: yr: Mnthly clinical examination, CXR alternate visitsMnthly clinical examination, CXR alternate visits22ndnd yr: yr: 2 mnthly clin exam, CXR alt visits2 mnthly clin exam, CXR alt visits33rdrd yr: yr: 3 mnthly clin exam, CXR alt visits3 mnthly clin exam, CXR alt visits44thth yr: yr: 4 mnthly clin exam4 mnthly clin exam55thth & 6 & 6thth yr: yr: 6 mnthly6 mnthly77thth yr onwards: yr onwards: Annual visitsAnnual visits
Tumour Markers (hCG, AFP, LDH, CA125)Tumour Markers (hCG, AFP, LDH, CA125)
0-6 months:0-6 months: 2 wkly2 wkly
7-24 months:7-24 months: 4 wkly4 wkly
25-36 months:25-36 months: 8 wkly8 wkly
37-60 months:37-60 months: 12 wkly12 wkly
> 5 yrs:> 5 yrs: 6 monthly6 monthly
> 10 yrs:> 10 yrs: AnnuallyAnnually
Stage Ia SurveillanceStage Ia Surveillance
Stage Ia Surveillance: Results 1981-2003Stage Ia Surveillance: Results 1981-2003
• 31 patients included (9 dysgerminomas, 22 NDGCTs)31 patients included (9 dysgerminomas, 22 NDGCTs)
4 mature teratomas + 2 Stage Ic excluded4 mature teratomas + 2 Stage Ic excluded
• median 26 yrs (range 14-48 yrs)median 26 yrs (range 14-48 yrs)
• 64% elevated pre-op hCG and/or AFP64% elevated pre-op hCG and/or AFP
• 1 dysgerminoma with bilat disease1 dysgerminoma with bilat disease
Patterson et al Int J Gynaecol Cancer 2008Patterson et al Int J Gynaecol Cancer 2008
Stage Ia Surveillance: Results 1981-2003Stage Ia Surveillance: Results 1981-2003
• median follow-up 6 yrs (range 5 m-21 yrs)median follow-up 6 yrs (range 5 m-21 yrs)• 10 relapses (32%)10 relapses (32%)
2 dysgerminomas (22%) 2 dysgerminomas (22%) 8 NDGCTs (36%)8 NDGCTs (36%)
Patterson et al Int J Gynaecol Cancer 2008Patterson et al Int J Gynaecol Cancer 2008
Location and Time of relapsesLocation and Time of relapses
• Pelvis:Pelvis: 6 (3 other ovary-1 dysgerminoma)6 (3 other ovary-1 dysgerminoma)
• Abdo:Abdo: 22
• Marker + ve:Marker + ve: 4 (2 marker only)4 (2 marker only)
• Latest relapse 13 mnths from surgeryLatest relapse 13 mnths from surgery
Patterson et al Int J Gynaecol Cancer 2008Patterson et al Int J Gynaecol Cancer 2008
Salvage treatmentsSalvage treatments
• 9/10 salvaged with chemo (90%)9/10 salvaged with chemo (90%)7 POMB/ACE (1 died despite surgery)7 POMB/ACE (1 died despite surgery)3 BEP x 3-43 BEP x 3-4
• 1 patient died 8 yrs later - melanoma1 patient died 8 yrs later - melanoma
Patterson et al Int J Gynaecol Cancer 2008Patterson et al Int J Gynaecol Cancer 2008
• 29/31 alive and in remission after median 6 yrs29/31 alive and in remission after median 6 yrs
• 5 yr disease free survival 68% (95% CI: 46-84%) 5 yr disease free survival 68% (95% CI: 46-84%)
• 5 yr overall survival 5 yr overall survival 93% (95% CI: 78-99%) 93% (95% CI: 78-99%)
• 5 yr DSS5 yr DSS 97% 97%
Stage Ia Surveillance: Results 1981-2003Stage Ia Surveillance: Results 1981-2003
Patterson et al Int J Gynaecol Cancer 2008Patterson et al Int J Gynaecol Cancer 2008
• CarboplatinCarboplatin
• EPEP
• DXTDXT
• BEPBEP
• Surgery??Surgery??
Stage Ia Adjuvant treatment?Stage Ia Adjuvant treatment?
Dysgerminoma vs NDGCT?Dysgerminoma vs NDGCT?
Carboplatin / EP/ BEP / DXT??Carboplatin / EP/ BEP / DXT?? AdvantagesAdvantages Disadvantages Disadvantages
Less relapsesLess relapses Still relapseStill relapse
Less surveillanceLess surveillance Surveillance still requiredSurveillance still required
Improved OS?Improved OS? Second cancers?Second cancers?
Cardiovascular?Cardiovascular?
Drug resistance?Drug resistance?
Reduced fertility?Reduced fertility?
Stage Ia Adjuvant Rx for OGCTs?Stage Ia Adjuvant Rx for OGCTs?
Stage Ia Adjuvant for Dysgerminomas?Stage Ia Adjuvant for Dysgerminomas?
Vicus et al Gynecol Oncol 2010Vicus et al Gynecol Oncol 2010
38 stage IA
15 Adjuvant 23 surveillance
11 DXT 4 BEP/EP
0 Relapses: 52 other ovary
3 abdo OS: 100% 100%
2nd cancer: 1 0
Williams et al JCO 1994Williams et al JCO 1994
93 patients93 patients60 stage 1, 10 stage 2, 23 stage 2360 stage 1, 10 stage 2, 23 stage 23
BEP > PVBBEP > PVB2 relapses after BEP NDGCT (1 dead 1??)2 relapses after BEP NDGCT (1 dead 1??)
1 stage Ic1 stage Ic2 patients 22 patients 2ndnd Cancers (1 death: AML) Cancers (1 death: AML)
Stage Ia Chemo for NDGCTs?Stage Ia Chemo for NDGCTs?
• No right answerNo right answer
• Costs are similarCosts are similar
• Surveillance is least toxicSurveillance is least toxic
• If patient can’t comply we give:If patient can’t comply we give:
- Carbo AUC 7 x 2 for DGCT- Carbo AUC 7 x 2 for DGCT
- BEP x 3 for NDGCT- BEP x 3 for NDGCT
• Long term monitoring required with bothLong term monitoring required with both
Stage Ia Adjuvant vs SurveillanceStage Ia Adjuvant vs Surveillance
• Lymphovascular invasionLymphovascular invasion
• Marker positiveMarker positive
• Very large tumoursVery large tumours
• Endodermal sinus and/or yolk sacEndodermal sinus and/or yolk sac
• Pure ChoriocarcinomaPure Choriocarcinoma
- Surveillance is still OK- Surveillance is still OK
What about poor prognostic features?What about poor prognostic features?
Case 1 example of Stage I surveillanceCase 1 example of Stage I surveillance
Pure seminoma
NSGCT
Chorio
CX Stage Ia Surveillance: Results 2003CX Stage Ia Surveillance: Results 2003
Fertility?Fertility?
• 30/31 had unilat oophrectomy30/31 had unilat oophrectomy• Non-relapsed group: Non-relapsed group: 50% (10/20) babies50% (10/20) babies• Relapsed group:Relapsed group: 50% (5/10) babies50% (5/10) babies
• Desire for pregnancy 75% (15/20)Desire for pregnancy 75% (15/20)
Patterson et al Int J Gynaecol Cancer 2008Patterson et al Int J Gynaecol Cancer 2008
Fertility with adjuvant therapy?Fertility with adjuvant therapy?
• DXT impairs fertilityDXT impairs fertility11/11 treated with DXT no pregnancies11/11 treated with DXT no pregnancies
• Carbo or BEP probably little effectCarbo or BEP probably little effect
Surveillance for stage Ic MOGCT?Surveillance for stage Ic MOGCT?
• Likely increased recurrence riskLikely increased recurrence risk
• Don’t currently do this at CXDon’t currently do this at CX
• Fertility conserving surgeryFertility conserving surgery
• Surveillance is reasonableSurveillance is reasonable- 22-36% relapse but nearly all cured- 22-36% relapse but nearly all cured
• Adjuvant therapy an alternativeAdjuvant therapy an alternative- for non-compliant pts- for non-compliant pts
- over-treats 75%- over-treats 75%
-22ndnd cancer risk cancer risk
• Relapses within 1-2 yrs in Relapses within 1-2 yrs in
pelvis/abdopelvis/abdo
• Fertility is high but not with DXTFertility is high but not with DXT
Summary for Stage IaSummary for Stage Ia
AcknowledgementsAcknowledgementsProf Edward S NewlandsProf Edward S NewlandsProf Fernando J ParadinasProf Fernando J ParadinasProf Gordon JS RustinProf Gordon JS RustinDr Philip SavageDr Philip SavageDr Iain LindsayDr Iain LindsayDr Iain McNeishDr Iain McNeishDr Nirupa MurugaesuDr Nirupa MurugaesuDr Daniel PattersonDr Daniel PattersonDr Roshan AgarwalDr Roshan AgarwalDr Adrian LimDr Adrian LimMs Linda DyallMs Linda DyallMs Sarah StricklandMs Sarah Strickland
Dr Edward KanferDr Edward KanferMr Richard SmithMr Richard SmithMr Angus McIndoeMr Angus McIndoeMrs Delia ShortMrs Delia ShortMrs Sandra FullerMrs Sandra FullerDr Lydia HoldenDr Lydia HoldenMr Hugh MitchellMr Hugh MitchellDr Richard HarveyDr Richard HarveyDr Adam MitchellDr Adam MitchellDr Joe BoultbeeDr Joe Boultbee
Wellcome TrustWellcome TrustCTRTCTRT
[email protected]@imperial.ac.uk