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Patterns of Care and Prognosis of Retroperitoneal Sarcomas in the Primary and Advanced Settings A Large Multicentric Retrospective Analysis from the French Sarcoma Group M. Toulmonde, E Stoeckle, S. Bonvalot, N. Isambert, E Bompas, N. Penel, V. Brouste, J-Y. Blay, S. Piperno-Neumann, C. Chevreau, P. Terrier, D. Ranchère-Vince, J-M. Coindre, B. Nguyen Bui, A. Italiano
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Retroperitoneal Sarcomas (RPS) Rare and heterogeneous Poor prognosis Heterogeneous data Controversies -Type of surgery -Role of radiotherapy Diversity of presentations in advanced setting
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Objectives Description of patterns of care Prognostic factors Subgroup analyses according to histological subtypes I) On a Large homogeneous cohort of patients with completely resected primary RPS II) In the advanced setting
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Patients and Methods Prospective database of the French Sarcoma Group Retrospective review of medical charts Patients ≥ 18 years with primary RPS Diagnosis between 01/01/1988 and 31/12/2008 Referred to one of 12 participating French Comprehensive Cancer Centers Systematic histological review by an expert pathologist member of the GSF-GETO Statistical analyses according to standard methods (Log- rank, Cox model)
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Results 586 patients Median follow-up = 6.5 years [5.9-7.1] 26 patients not operated 19 patients initial abdominal sarcomatosis 30 patients initial distant metastasis 586 patients 537 patients M0 511 patients operated 110 patients R2 12 patients unknown resection status 389 patients R0/R1
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Characteristics at diagnosis Patients (n=586) % Median age 57 years (18- 89) Sex ratio M/F 0.87 Median tumor size 17 cm (4-85) Histology DDLPS WDLPS LMS US Other 244 135 109 42 56 41.5% 23% 18.5% 7% 10% Grade 1 2 3 NS 152 244 179 11 26% 41.5% 30.5% 2% Multifocality9516% LR involvement24842% Vascular involvement 6010% DDLPS: Dedifferentiated Liposarcoma WDLPS: Well-Differentiated Liposarcomas LMS: Leiomyosarcomas US: Unclassified Sarcomas Other: Other subtypes LR: Locoregional
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Patients (n=511) % Type of surgery Simple Large Compartmental NS 189 200 120 2 37% 39% 24% - Expert surgeon22243.5% Complete resection38976% Tumor rupture8015.5% ≥1 resected organ33265% Perioperative RT14629% Perioperative CT8917% Initial treatment modalities Patients (n=586) % Preoperative biopsy 23440% Pretherapeutic multidisciplinary assessment 16528%
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Evolution (389 patients R0/R1) 5-year LR relapse-free Survival = 46% [41-52] 0 25 50 75 100 01234567891011 Time (years) 38932625819713894705241262013 Number at risk 95% CI LR relapse-free Survival Probability
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Evolution (389 patients R0/R1) 0 25 50 75 100 01234567891011 Time (years) 3893703392942331691219680584538 Number at risk 95% CI Overall Survival Probability Overall Survival 5-year overall survival = 66% [61-71]
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Predictive factors for complete surgery (511 patients operated ) Multivariate analysis OR[I95%CI] (p) Histology (WDLPS) DDLPS LMS US Other 2.4 0.3 1.5 2.8 [1.1-4.9 [0.08-0.91] [0.46-4.8] [0.99-8.1] (p= 0.02) (p= 0.03) (p= 0.5) (p= 0.05) GradeNot significant Multifocality3 [1.4-6.3] (p= 0.005) LR involvement14.1 [5.8-34.4] (p<0.001) Type of surgery (simple) Compartmental Large 0.02 0.04 [0.005-0.9] [0.02-0.1] (p<0.001) Expert Surgeon0.3 [0.12-0.6] (p=0.001)
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Prognostic factors for LR relapse Multivariate analysis HR[95%CI](p) Male sex1.5 [1.1-2] (p=0.006) Histology Not significant Grade Not significant LR involvement1.6 [1.2-2.1] (p=0.004) Type of surgery Not significant Expert Surgeon0.5 [0.4-0.7] (p<0.001) Tumor rupture2.9 [1.9-4.5] (p<0.001) Perioperative RT0.5 [0.4-0.7] (p<0.001) 0 50 100 01357911 Time (years) LR relapse-free survival according to surgeon’s expertise No expert surgeon Expert surgeon 0 50 100 01357911 Time (years) LR relapse-free survival according to perioperative radiotherapy No perioperative radiotherapy Perioperative radiotherapy
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Prognostic factors for abdominal sarcomatosis Multivariate analysis HR[95%CI] (p) Grade (1) 2 3 1.4 2.1 [0.7-3.0] [1.0-4.6] (p=0.4) (p= 0.05) LR involvement1.8 [1.0-3.1] (p=0.04) Expert surgeon0.5 [0.3-0.9] (p=0.02) Tumor rupture4.2 [2.2-7.9] (p<0.001) 0 50 100 01357911 Sarcomatosis-free survival according to tumor rupture Tumor rupture No tumor rupture Time (years)
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Prognostic factors for distant metastasis Multivariate analysis HR[95%CI] (p) Tumor size < 18 cmNot significant Histology (WDLPS) DDLPS LMS US Other 2.6 11.9 3.1 9.6 [1.1-6.2] [5.3-26.9] [0.8-12.3] [3.8-24.1] (p=0.027) (p<0.001) (p=0.1) (p<0.001) GradeNot significant LR involvement1.6 [1-2.5] (p=0.034) Vascular involvement Not significant Perioperative RTNot significant 0 50 100 01357911 Time (years) DDLPS WDLPS LMS US Others Distant metastasis-free survival according to histology
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Prognostic factors for overall survival Multivariate analysis HR[95%CI] (p) Age ≥ 56 years1.4 [1-1.9] (p=0.04) Male sex1.7 [1.3-2.3] (p<0.001) HistologyNot significant Grade (1) 2 3 2.1 4.1 [1.4-3.2] [2.7-6.2] (p=0.001) (p<0.001) LR involvement1.6 [1.2-2.2] (p=0.002) Tumor rupture2 [1.3-3] (p=0.002) 0 50 100 01357911 Time (years) Overall survival according to tumor rupture Tumor rupture No tumor rupture Time ( years ) 0 50 100 01357911 grade 1 grade 3 grade 2 Overall survival according to grade
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Sub-group analysis according to histology for LR relapse Multivariate analysis HR[95%CI] (p) WDLPS Tumor size ≥ 18 cm 2.6 [1.2-6] (p=0.02) Tumor rupture4 [1.6-9.7] (p=0.002) DDLPS Expert surgeon0.6 [0.4-0.9](p=0.01) Perioperative RT0.6 [0.4-0.9](p=0.028) LMS Tumor rupture10.1 [3.3-30.5](p<0.001)
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Sub-group analysis according to histology for OS Multivariate analysis HR[95%CI] (p) WDLPS Age ≥ 56 years3.3 [1.5-7.5] (p=0.004) Multifocality3.1 [1.2-8.3] (p=0.02) LR involvement2.3 [0.97-5.5] (p=0.05) DDLPS Male sex1.8 [1.1-2.8](p=0.014) Grade 31.8 [1.1-2.8](p=0.015) Tumor rupture2.3 [1.2-4.2](p=0.008) LMS LR involvement2.4 [1.1-5.6](p=0.035) Type of surgery Simple Compartmental 1.8 2.5 [0.7-4.5] [1.2-5.3] (p=0.2) (p=0.018)
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Patterns of care in advanced stage 299 patients palliative CT for advanced disease 586 patients 50 patients palliative surgery First line palliative CT - Monotherapy = 49% -Anthracycline-based = 75% Median number of line = 2 (1-8) -33% received ≥ 3 lines
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OS from first line of palliative CT Median Overall Survival All 15.8 months[13-18] WDLPS26.8 months[12-65] LMS19.6 months [16-25] US14.4 months[6-19] DDLPS13.5 months [11-17] Other11.8 months[5-16] 0 25 50 75 100 012345678910 Time (years) 2991688544281242100 Number at risk 95% CI Overall survival Overall Survival
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OS from first line of palliative CT Median Overall Survival All 15.8 months[13-18] WDLPS26.8 months[12-65] LMS19.6 months [16-25] US14.4 months[6-19] DDLPS13.5 months [11-17] Other11.8 months[5-16] DDLPS WDLPS LMS US Other 0 25 50 75 100 013579 Time (years) Overall survival according to histology
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Prognostic Factors for overall survival from first line of palliative CT Multivariate analysis HR[95%CI] (p) Male sex1.5[1.1-1.9] (p=0.009) PS (0) 1 ≥ 2 1.7 3 [1.2-2.2] [1.9-4.8] (p=0.001) (p<0.001) Grade (1) 2 3 1.7 2.3 [1.1-2.7] [1.5-3.7] (p=0.02) (p<0.001) Histology Not significant 0 50 100 01 3 579 Time (years) Overall survival according to grade grade 1 grade 3 grade 2 0 50 100 013579 Time (years) PS = 0 PS =1 PS ≥ 2 Overall survival according to PS Stage of the disease Palliative surgery no difference
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Discussion Predominance of DDLPS Poor conformity to practice guidelines Surgical expertise is a major prognostic factor DDLPS WDLPS LR involvement and OS LMS limits of surgery on OS Need for histology-specific clinical trials - Radiotherapy and LR relapse - Grade and OS
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Acknowledgements V. Brouste J-B. Courrèges E. Stoeckle G. Kantor A. Neuville J-M. Coindre B. Nguyen Bui A. Italiano O. Riou N. Isambert E Bompas N. Penel C. Delcambre-Lair F. Duee E. Saada M. Jean-Denis P. Terrier D. Ranchère-Vince A. Lecesne S. Bonvalot J-Y. Blay S. Piperno-Neumann C. Chevreau J-O. Bay A. Thyss
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Survivals according to histology LR relapse-free survival [95%CI] Distant metastasis-free survival [95% CI] overall survival [95%CI] At 5 yearsAt 10 yearsAt 5 yearsAt 10 yearsAt 5 yearsAt 10 years WDLPS53% [42-63]21% [10-35]96% [90-99]94% [87-98]92% [84-96]63% [47-75] DDLPS40% [32-49]24% [14-36]86% [79-91]81% [70-88]61% [52-68]31% [21-42] LMS55% [42-67] 47% [34-59]28% [14-43]61% [49-72]30% [16-44] US25% [9-46]-73% [34-91]-35% [14-57]- Other48% [28-66] 63% [43-78]55% [32-74]43% [26-59]31% [14-50]
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Sub-group analysis according to histology for overall survival after first line palliative CT Multivariate analysis HR[95%CI] (p) DDLPS PS (0) 1 ≥ 2 1.6 2.96 [1-2.5] [1.3-6.8] (p=0.04) (p=0.01) Grade (1*and 2) 31.7[1.1-2.6] (p=0.03) LMS PSNot significant Grade (1) 2 3 3535 [1.1-9.2] [1.6-15.4] (p=0.037) (p=0.005) Stage (LR) Sarcomatosis Distant metastasis 0.8 0.4 [0.3-2] [0.2-0.7] (p=0.59) (p=0.003)
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0 25 50 75 100 01234567891011 Time (years) 38932625819713894705241262013 Number at risk 95% CI LR-free Survival LR relapse- free Survival (Probability)
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111501694321000grade_pal = 3 12575462114410000grade_pal = 2 463016107311100grade_pal = 1 Number at risk grade_pal = 1grade_pal = 2 grade_pal = 3 0 50 100 01 3 579 Time (years) Overall Survival according to grade grade 1 grade 3 grade 2
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288100000000ps_pal_recup_2c = 2 ou 3 974722104100000ps_pal_recup_2c = 1 15098593122942100ps_pal_recup_2c = 0 0 25 50 7575 100 Number at risk 013579 Time (years) PS = 0 PS =1 PS ≥ 2 Overall Survival according to PS
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Sub-group analysis according to histology WDLPS LR Relapse HR[95%CI] (p) Tumor size ≥ 18 cm 2.6[1.2-6] (p=0.02) Expert surgeonNot significant Tumor rupture4[1.6-9.7] (p=0.002) Perioperative RTNot significant Overall survival Age ≥ 56 years3.3[1.5-7.5] (p=0.004) Multifocality3.1[1.2-8.3] (p=0.02) LR involvement2.3[0.97-5.5] (p=0.05) DDLPS LR RelapseHR[95%CI](p) Expert surgeon0.6[0.4-0.9](p=0.01) Perioperative RT0.6[0.4-0.9](p=0.028) Overall survival Age ≥ 56 yearsNot significant Male sex1.8[1.1-2.8](p=0.014) Grade 31.8[1.1-2.8](p=0.015) Tumor rupture2.3[1.2-4.2](p=0.008) LMS LR RelapseHR[95%CI](p) Tumor rupture10.1[3.3-30.5](p<0.001) Overall survival LR involvement2.4[1.1-5.6](p=0.035) Type of surgery (large) Simple Compartmental 1.8 2.5 [0.7-4.5] [1.2-5.3] (p=0.2) (p=0.018)
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