대한부인종양콜포스코피학회제 24 차학술대회 Correlation of intermediate risk factors with prognostic factors in patients with early cervical cancer Seoul National University Bundang Hospital Eun Jung Soh, M.D.
Cervical cancer The 3 th most common cancer in women worldwide. Early cervical cancer (FIGO stage IA2~IIA) Surgery or Radiotherapy Overall survival rate at 5 years; 80% 90% But, Many other factors influence to treatment outcome. Parkin et al 2005 CA cancer J clin Samlal RA,et al1999.(ejog Reprod Biol)
Prognostic factors in early stage cervical cancer High risk factors Positive or close margins Positive lymph nodes Microscopic parametrial involvement Intermediate-risk factors Large mass size Deep cervical stromal invasion Lymph-vascular space invasion Fuller AF, et al. (Gynecol Oncol) 1989 Delgado G, et al. (Gynecol Oncol) 1990
Adjuvant treatment with risk factors
Objective To investigate the prognostic significance of intermediate risk factors such as large mass size, deep stromal invasion, lymphovascular space invasion and their correlation with high risk factors.
Patients and methods Patients 105 patients with cervical cancer stage la2- lla Radical hysterectomy between 2003 and 2007 at SNUBH Adjuvant therapy if indicated Intermediate risk score Definition of Intermediate risk factor Large mass size (> 4cm) Deep cervical stromal invasion ( 50%) Lymph-vascular space invasion Scoring of number of intermediate risk factor (0 to 3)
Results
Association of clinicopathologic factors with intermediate risk score 0 (n=30) n (%) Score of intermediate risk factors 1 (n=27) 2 (n=22) n (%) n (%) 3 (n=26) n (%) P Age <50 14 (46.7%) 14 (51.9%) 11 (50.0%) 13 (50.0%) 50 16 (53.3%) 13 (48.1%) 11 (50.0%) 13 (50.0%) 0.983 * Stage 1a2 1 (3.3%) 1 (3.7%) 0 (0%) 0 (0%) 1b1 27 (90.0%) 16 (59.3%) 3 (13.6%) 0 (0%) < 0.001 1b2 0 (0%) 2 (7.4%) 8 (36.4%) 10 (38.5%) 2a 2 (6.7%) 8 (29.6%) 11 (50.0%) 16 (61.5%) Histologic type Squamous 25 (83.3%) 17 (63.0%) 17 (77.3%) 21 (80.8%) 0.50 * others 5 (16.7%) 10 (37.0%) 5 (22.7%) 5 (19.2%) Adjuvant Tx. No 28 (93.3%) 14 (51.9%) 5 (22.7%) 3 (11.5%) Yes 2 (6.7%) 13 (48.1%) 17 (77.3%) 23 (88.5%) < 0.001 * Recur No 28 (93.3%) 26 (96.3%) 20 (90.9%) 23 (88.5%) 0.74 * Yes 2 (6.7%) 1 (3.7%) 2 (9.1%) 3 (11.5%) n = number of case, % = % of case within risk score. *= Chi-square test. =linear-by-linear association.
Correlation with intermediate risk score and high risk factors Patients with positive high risk factors(%) 100% 80% p < 0.001 60% 40% 29.6% 20% 0% 0.0% 84.6% 68.2% 0 (0/30) 1 (8/27) 2 (15/22) 3 (22/26) Intermediate risk score(case/total) Correlation with intermediate risk score & number of high risk factors 1.4 1.2 1 0.8 0.6 0.4 0.2 0 p < 0.001 0 0.41 1 0 1 2 3 1.4 Intermediate risk score
Correlation with intermediate risk score and high risk factors Patients of positive prametrial invasion (%) Patients of resection margin involvement(%) 100% 20% 80% 60% p < 0.001 65.4% 15% p < 0.025 15.4% 40% 40.9% 10% 20% 25.7% 5% 4.5% 0% 0.0% 0 (0/30) 1 (3/27) 2 (9/22) 3 (17/26) Intermediate risk score(case/total) 0% 0.0% 0.0% 0 (0/30) 1 (0/27) 2 (1/22) 3 (4/26) Intermediate risk score(case/total)
Increasing of LN involvement with intermediate risk score 80% 60% Patients with LN involvement (%) 65.4% p < 0.001 54.5% 40% 29.6% 20% 0% 0.0% 0 (0/30) 1 (8/27) 2 (12/22) 3 (17/26) Intermediate risk score(case/total) Mean LN number according to intermediate risk score 5 4 3 2 1 0 p = 0.023 0 1.7 2.6 4.4 0 1 2 3 Intermediate risk score
Treatment Plan Considering Risk Factor Stage IA2~IIA -> RH c PLND High risk factors(+) ; Adjuvant CCRT High risk factor(-) Intermediate risk factors(+) ; Adjuvant therapy Intermediate risk factor(-) ; Observation
Conclusion Number of intermediate risk factors was statically significant associated with presence of high risk factors. Our intermediate risks scoring system 1. Patients with intermediate risk factors are more favorable to receive adjuvant treatment even if without high risk factor. 2. Incidental early cervical cancer patients without any intermediate risk factor after simple hystrectomy can be observed instead of reoperation.
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Patients with Intermediate risk factor Schorge JO, et al. in 1997 Recurrence with no difference between radical hysterectomy(rh) and RH+RT. Alexander S, et al. in 1999 Adjuvant pelvic RT reduced recurrence from 28% to 15% at 2 years after treatment. Ayhan A, et al. in 2004 Adjuvant RT in stage IB cervical cancer with negative node provides no survival advantage.
Study for correlation of intermediate risk factor with LN metastasis Journal LVSI DSI Size Gauthier P, et al. (1985) Fuller AF, et al. (1989) Delgado G, et al. (1989) NS S NS S a S a S a S S S LN ; lymph node, LVSI ; lympho-vascular space invovement, DSI ; deep stromal invasion. NA ; not analysis, S ; significant, NS ; not significant. a ; as determined by univariate analysis
Scoring of intermediate risk factor Gauthier P, et al. in 1985 Grouping Factors 5yr survival Low Intermediate 2cm sized 2.1~3cm + 1.5cm invasion 2.1~3cm + >1.5cm invasion > 3cm sized + 1.5cm invasion 97% 71% High > 3cm sized + > 1.5cm invasion 31% G. Delgado, et al. in 1990 A. Sedlis, et al. in 1999 LVSI Stromal invasion Tumor size Positive Positive Positive Negative Deep 1/3 Middle 1/3 Superficial 1/3 Deep or middle 1/3 Any 2cm 5cm 4cm
A Gynenologic Oncology Group Study in 1990
Scoring of intermediate risk factor Gauthier P, et al. in 1985 Grouping Factors 5yr survival Low Intermediate 2cm sized 2.1~3cm + 1.5cm invasion 2.1~3cm + >1.5cm invasion > 3cm sized + 1.5cm invasion High > 3cm sized + > 1.5cm invasion 31% 97% 71% G. Delgado, et al. in 1990 A. Sedlis, et al. in 1999 LVSI Stromal invasion Tumor size Positive Positive Positive Negative Deep 1/3 Middle 1/3 Superficial 1/3 Deep or middle 1/3 Any 2cm 5cm 4cm
Correlation with recurrence rate with intermediate risk score Score of intermediate risk factors 0 (n=30) n (%) 1 (n=19) n (%) 2 (n=7) n (%) 3 (n=4) n (%) P No high risk yes 2 (6.7%) 1 (5.3%) 2 (28.6%) 0 (0%) 0.738 no 28 (93.3%) 18 (94.7%) 5 (71.4%) 4 (100%) Score of intermediate risk factors 0 (n=28) n (%) 1 (n=13) n (%) 2 (n=4) n (%) 3 (n=2) n (%) P No high risk + No Adjuvant Tx. yes 1 (3.6%) 0 (0%) 2 (50.0%) 0 (0%) 0.003 no 27 (96.4%) 13 (100%) 2 (50.0%) 2 (100%)
The Global Burden of Cancer to Women Worldwide Parkin DM et al CA Cancer J Clin 2005;55;74-108