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MULTICENTRIC EVALUATION OF THE FRENCH SURGICAL SYSTEM IN SOFT TISSUE SARCOMA (STS).

E. Stoeckle, S. Bonvalot, JY Blay, L. Guillou, J. Fraisse, JL.

Verhaeghe, JM. Coindre, BN Bui

From the French Sarcoma Group

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Why another classification?

Surgery is no more the only treatment for STS: Formerly, subjectivity of surgeon-based definitions of quality

of surgery had no impact on treatment modalities: wait and see

Actually, multimodality treatment needs to know: - who will recur - to whom give additional treatment and how

Furthermore, homogenous treatment reporting is needed However, quality of surgery remains subjective:

Surgeon – dependent or Pathologist - dependent

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The UICC classification The UICC recommends the R -

classification in STS: R0: resection in sano R1: microscopic residual disease R2: macroscopic residual disease

But it does not give instructions how to determine R!

Usually, Enneking’s classification is transposed into the R - classification

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4Individual appreciation of quality of surgery is not

appropriate!

Surgeons overestimate excision Almost large German registry (Junginger 2001):

Extremity sarcoma 82% R0 Retroperitoneal sarcoma 64% R0

Local recurrences remain elevated Pathologists underestimate excision

Retraction of tissue Negative specimen after re-excision in 50%

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The FSG system (I)1. 1995: OP reports review in 8 participating

centers: missing information2. 1995 - 1996: multicentric feasibility study of

items for OP reporting: Only describe Important issues: tumor seen?

tumor rupture?3. 1998: Recommendations for pathology reporting

(Ghnassia).4. Determination of resection type (UICC R system)

by surgeon and pathologist.

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The FSG system (II)

4. 1996 - 1999: prospective validation in a single center (Bordeaux):

109 consecutive patients with trunk wall + extremity, conservative surgery, 68% R0 , 56 months FU:

3% R0Local recurrence:8% (P < 0,01)

19% R1 Negative predictive value of R0: 97%

5. Actual study: multicentric evaluation

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Methods Methods:

FSG data base - multivariate prognostic factor analysis Patients’ selection:

resection type (R) informed: 423 pts. 325 pts. with trunk wall or extremity STS 302 pts. N0 M0

Inclusion and follow-up: 1995 - 2002, FU: 21 months (1 – 104 months)

Accrual by center: Bordeaux 88 Villejuif 52 Lyon 52 Lausanne 24 Nancy 22 0ther centers 64

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Patients’ characteristics

M/F: 150/152 pts. Localizations:

Shoulder girdle 12 4% Upper extremity 36 12% Trunk wall 31 10% Pelvic girdle 24

8% Lower extremity 199 66%

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Tumor extension

Superficial tumors: 56 pts. (18,5%) Median size : 9 cm (1 – 26 cm) Multifocality: 31 pts. (10,3%) Vasc./nerve involvement: 47 pts. (15,6%) AJC/UICC stage 1979:

I: 14% II: 28% III: 33% IV: 15% NP: 10% AJC/UICC stage 2002:

IA: 15% IB: 35% IIA: 13% IIB: 2% III: 29% NP: 5%

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Pathology

Histological subtypes: Liposarcoma 70 (23%) Leiomyosarcoma 46 (15%) MFH 44 (15%) Synovialosarcoma 25 (8%) MPNST + RhabdoS. 15 (5%) Unclassified S. 39 (13%) Others + NP 63 (21%)

Grade I: 17% II: 34% III: 45% NP: 5%

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Treatments

302 operated patients: First-line surgery:83% Resection types :

R0 220 (73%)R1 68 (22%)R2 14 (5%)

Radiotherapy:62% Chemotherapy: 40%

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Treatment results

R0 213

CR: 272 (90%) R1 54

R2 5

Survivors: 240 (80%) actuarial 65%

LR: crude 34 (13%) actuarial 21%

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Overall survival

TSURV

60483624120

Sur

vie

cum

ulée

1,0

,9

,8

,7

,6

,5

,4

,3

,2

,1

0,0

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Resection-type according to center (NS)

Center N R0

Bordeaux 88 73%Villejuif 52 73%Lyon 52 64%Lausanne 24 83%Nancy 22 64%Others 64 80%

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Resection type according to localization (NS)

Localization N R0

Shoulder girdle 12 75%Upper extremity 36 56%Trunk wall 31 71%Pelvic girdle 24 67%Lower extremity 199 77%

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Local recurrence-free interval

TRLOC

60544842363024181260

Sur

vie

cum

ulée

1,0

,9

,8

,7

,6

,5

,4

,3

,2

,1

0,0

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Local recurrence according to R

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1

0 12 24 36 48 60 72

R0R1+R2

P = 0,004

R0

R1 + R2

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Local recurrence according to grade

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1

0 12 24 36 48 60 72

grade1 et2grade3

P = 0,019

Grade 1 + 2

Grade 3

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19Local recurrence according to T3 (1979 UICC

classification)

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1

0 12 24 36 48 60 72

T1T2T3

P = 0,049T1 + T2

T3

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Local recurrence according to stage AJC/UICC 1979

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1

0 12 24 36 48 60 72

stade I ajcstade 2 ajcstade3 ajcstade4 ajc

P = 0,0045

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Local recurrence according to stage AJC/UICC 2002

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1

0 12 24 36 48 60 72

stade IA2002stade IB2002Stade II 2002Stade3 2002

P = 0,042

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Prognostic factors/LRVariable RL N p

R R0 20 213 0,004R1+R2 14 59

Grade 1 3 46 0,022 7 923 23 122

T T1 +T2 23 218 0,05T3 8 37

Histotype, Size (+/- 5 cm), Localization,Depth, Center, Radiotherapy: NS

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Independent prognostic factors for local recurrence

Variables p RR CI

No R0 0,003 3,06 1,47 - 6,38

Grade 3 0,004 3,35 1,48 - 7,55

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Conclusion

Resection type (R) as defined by FSG predicts independently local recurrence

FSG criteria are reproducible and can be used in a multicentric setting

Treatment results in the multicenter study are lower than in the single center: progress still needed.