Advanced Vulva Cancer

Mansoor Raza MirzaMansoor Raza MirzaDept. of OncologyDept. of Oncology

Odense University HospitalOdense University HospitalOdense, DenmarkOdense, Denmark

Radiotherapy forRadiotherapy forAdvanced Vulva Advanced Vulva

CancerCancer

Stage III Stage III Tumor with adjacent spread to urethra, Tumor with adjacent spread to urethra,

vagina or anus vagina or anus or with unilateral lymphnode metastasesor with unilateral lymphnode metastases

Stage IVaStage IVaTumor invades upper urethra, bladder Tumor invades upper urethra, bladder

mucosa, rectal mucosa or pelvic bonemucosa, rectal mucosa or pelvic boneor bilateral node metastasesor bilateral node metastases

Stage IVbStage IVbDistant metastasesDistant metastases

Definition of Advanced Definition of Advanced Vulva CancerVulva Cancer

Kehrer E. Kehrer E. Soll das Vulvakarzinom operiert oderSoll das Vulvakarzinom operiert oder

bestrahlt werden? bestrahlt werden? Geburtshilfe Frauenheilkunde 48:346; 1918Geburtshilfe Frauenheilkunde 48:346; 1918

Disease extended beyond the boundaries Disease extended beyond the boundaries of surgical feasibilityof surgical feasibility

Radiotherapy was administered using Radiotherapy was administered using suboptimal dose /fractionation schedules suboptimal dose /fractionation schedules as well as primitive techniquesas well as primitive techniques

Boronow RC, Cancer, 1982; 49: 1085-91Boronow RC, Cancer, 1982; 49: 1085-91

n = 37n = 37

Median radiation dose 48 GyMedian radiation dose 48 Gy

No residual disease in 42% patients at No residual disease in 42% patients at the time of surgerythe time of surgery

5 yr. survival 75,6%5 yr. survival 75,6%

Stehman FB et al., IJROBP, 1992; 24: 389-Stehman FB et al., IJROBP, 1992; 24: 389-9696

Randomized Controlled Trial - GOGRandomized Controlled Trial - GOG

Radiotherapy vs SurgeryRadiotherapy vs Surgery

TT1-31-3 N N0-10-1 M M00

n=58 (27 in Rt arm)n=58 (27 in Rt arm)

Radiotherapy: 50 Gy at 3cmRadiotherapy: 50 Gy at 3cm

Results:Results:

Groin recurrence 5/27 (18.5%)Groin recurrence 5/27 (18.5%)

OS: 60% vs 86%OS: 60% vs 86%

Stehman FB et al., IJROBP, 1992; 24: 389-Stehman FB et al., IJROBP, 1992; 24: 389-9696

Manavi M et al., IJROBP, 1997; 38: 749-53Manavi M et al., IJROBP, 1997; 38: 749-53

Case control study Case control study

Radiotherapy vs ‘wait and see’Radiotherapy vs ‘wait and see’

TT11 N N0-10-1 M M00

n=135 (65 received Rt)n=135 (65 received Rt)

Radiotherapy: 45Gy at 5cm telecobaltRadiotherapy: 45Gy at 5cm telecobalt

Results:Results:

Groin recurrence 3/65 (4.6%)Groin recurrence 3/65 (4.6%)

OS: 93.7% vs 91.4%OS: 93.7% vs 91.4%

Manavi M et al., IJROBP, 1997; 38: 749-53Manavi M et al., IJROBP, 1997; 38: 749-53

Perez CA et al., IJROBP, 1998; 42: 335-44Perez CA et al., IJROBP, 1998; 42: 335-44

Observational Observational

TT1-31-3 N N0-30-3 M M00

n=68+18n=68+18

LE+Rt 14; Rt 19+18; RV+Rt 24; PV+Rt 11LE+Rt 14; Rt 19+18; RV+Rt 24; PV+Rt 11

Radiotherapy: 50-70Gy at 4cmRadiotherapy: 50-70Gy at 4cm

Results:Results:

Groin recurrence 10%Groin recurrence 10%

OS: ?OS: ?

Perez CA et al., IJROBP, 1998; 42: 335-44Perez CA et al., IJROBP, 1998; 42: 335-44

Van der Velden J, Ansink A, Van der Velden J, Ansink A, The Cochrane Database of Systemic The Cochrane Database of Systemic

Reviews Reviews Stehman FB et al.Stehman FB et al.Manavi M et al.Manavi M et al.Perez CA et al.Perez CA et al.

Conclusions:Conclusions:

Primary radiotherapy to the groin results in less morbidity Primary radiotherapy to the groin results in less morbidity but also in a higher number of groin recurrences but also in a higher number of groin recurrences compared with surgery. compared with surgery.

Surgery is still to be considered the cornerstone of therapySurgery is still to be considered the cornerstone of therapyfor the groin nodes. for the groin nodes.

Katz A et al., IJROBP, 2003; 57: 409-418Katz A et al., IJROBP, 2003; 57: 409-418

Retrospective analysis of one centre dataRetrospective analysis of one centre data

1980-1998 1980-1998

n=227 (stage III/VI 119; Stage I/II 67)n=227 (stage III/VI 119; Stage I/II 67)

LND 119; LND+Rt 57; Rt 51LND 119; LND+Rt 57; Rt 51

Radiotherapy:Radiotherapy:narrow inguinal fieldsnarrow inguinal fields

45/50Gy or 60Gy45/50Gy or 60Gy

Surgery:Surgery: superficial LNDsuperficial LND

Results: Results:

5 yrs groin recurrence: 16% vs 13% vs 16%5 yrs groin recurrence: 16% vs 13% vs 16%

OS: ?OS: ?

Moore DH et al., IJROBP, 1998; 42: 79-85Moore DH et al., IJROBP, 1998; 42: 79-85Montana GS et al., IJROBP, 2000; 48: 1007-Montana GS et al., IJROBP, 2000; 48: 1007-

1313Preoperative chemo-radiation (GOG) Preoperative chemo-radiation (GOG)

TT3-43-4 or N or N2-32-3

n=73+46n=73+46

Radiotherapy: Split courseRadiotherapy: Split course47,6Gy in 6-6.5 weeks47,6Gy in 6-6.5 weeks

Chemotherapy: Cis+5-FuChemotherapy: Cis+5-Fu

Response evaluation: 4-8 wks after end of treatmentResponse evaluation: 4-8 wks after end of treatment

Results:Results:Complete clinical remission 46.5% and 43%Complete clinical remission 46.5% and 43%

Primary radical Primary radical chemoradiotherapychemoradiotherapy

AuthorAuthorNN

Stage (n)Stage (n)

ChemoChemo--

theraptherapyy

RT dose RT dose (Gy)(Gy)

CompleteComplete

ResponseResponseLater Later

relapserelapse NEDNED

Thomas Thomas ((Gynecol Oncol 1989;34:263–7))

99 (advanced)(advanced) F,MF,M 40-6440-64 6 (67%)6 (67%) 33 N/AN/A

BerekBerek(Gynecol Oncol, (Gynecol Oncol, 1991; 42: 197-1991; 42: 197-201)201)

12 12

(III-8; IV-4)(III-8; IV-4) F,PF,P 44-5444-54 8 (67%)8 (67%) 00 7-607-60

RussellRussell (Gynecol (Gynecol Oncol, 1992; 47: Oncol, 1992; 47: 14-20)14-20)

1818 (II-1; III- (II-1; III- 10; IV-6)10; IV-6) F,P,MF,P,M 46,8-5646,8-56 16 (89%)16 (89%) 22 2-522-52

Koh Koh (Int J Radiat Oncol (Int J Radiat Oncol Biol Phys, 1993; Biol Phys, 1993; 26: 809-16)26: 809-16)

14 14

(III-4; IV-10)(III-4; IV-10) F,P,MF,P,M 34-63,134-63,1 8 (57%)8 (57%) 11 5-755-75

Cunningham Cunningham (Gynecol Oncol, (Gynecol Oncol, 1997; 66: 258-61)1997; 66: 258-61)

14 14

(III-9; IV-5)(III-9; IV-5) F,PF,P 50-6550-65 9 (64%)9 (64%) 11 7-817-81

Eifel Eifel (Gynecol Oncol, (Gynecol Oncol, 1995; 59: 51-6)1995; 59: 51-6)

1212 (II-1; (II-1; III/IV-11)III/IV-11) F,PF,P 40-5040-50 6 (50%)6 (50%) 11 17-3717-37

TotalTotal 7979 53 (67%)53 (67%) 8 (15%)8 (15%)

Radical chemoradiotherapy for Radical chemoradiotherapy for relapserelapse

AuthorAuthor NN ChemoChemo-therpy-therpy

RT dose RT dose (Gy)(Gy)

CompleteComplete

responseresponseLatter Latter

relapserelapse NEDNED

ThomasThomas ((Gynecol Oncol 1989;34:263–7)) 1515 F,MF,M 40-6440-64 88 00 N/AN/A

Russell Russell (Gynecol Oncol, (Gynecol Oncol, 1992; 47: 14-20)1992; 47: 14-20) 77 F,PF,P 54-7254-72 44 11 2-352-35

TotalTotal 2222 12 12 (55%)(55%) 11

Meta-analysis:

Van Doorn et al. The Cochrane Library, issue 4, 2002, Oxford

The NSGO trialThe NSGO trialNSGO – CC – 0301NSGO – CC – 0301

FIGO III & IV or unfavourably located lesion

or relapsed vulvar cancer

Locoregional RadiotherapyLocoregional Radiotherapywithwith

Concomitant chemoterapyConcomitant chemoterapy

Surgical resection of Surgical resection of any residual diseaseany residual disease

Surgical resection of local tumorSurgical resection of local tumorif possibleif possible

• Subclinical target volume (T & N site)Subclinical target volume (T & N site)50 - 56 Gy (<2 Gy/fraction)50 - 56 Gy (<2 Gy/fraction)

• Gross tumor volumeGross tumor volumeMin. 60 Gy (2 Gy/fraction)Min. 60 Gy (2 Gy/fraction)

Adequate doseAdequate dose

Adequate target Adequate target volumevolume

Adequate target Adequate target volumevolume

Necessary depthNecessary depth

Concomitant weekly cisplatin 40 mg/m2Concomitant weekly cisplatin 40 mg/m2

Concomitant radio-Concomitant radio-chemotherapychemotherapy

12 weeks after end of treatment12 weeks after end of treatment

When to evaluate resultsWhen to evaluate results

Dept. of OncologyDept. of OncologyOdense University HospitalOdense University Hospital

Odense, DenmarkOdense, Denmark

Thank youThank you