Caroline E Poorman1, Cecilia G Ethun1, Lauren M Postlewait1, Thuy B Tran2, Jason D Prescott3, Timothy M Pawlik3, Tracy S Wang4, Jason Glenn4, Ioannis Hatzaras5, Rivfka Shenoy5, John E Phay6, Kara Keplinger6, Ryan C Fields7, Linda X Jin7, Sharon M Weber8, Ahmed Salem8, Jason K Sicklick9, Shady Gad9, Adam C Yopp10, John C Mansour10, Quan-Yang Duh11, Natalie Seiser11, Carmen C Solórzano12, Colleen M Kiernan12, Konstantinos I Votanopoulos13, Edward A Levine13, Charles A Staley1, George A Poultsides2, Shishir K Maithel14,15. 1. Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA. 2. Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA. 3. Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. 4. Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA. 5. Department of Surgery, New York University School of Medicine, New York, NY, USA. 6. Department of Surgery, The Ohio State University, Columbus, OH, USA. 7. Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA. 8. Department of General Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. 9. Department of Surgery, University of California San Diego, San Diego, CA, USA. 10. Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA. 11. Department of Surgery, University of California San Francisco, San Francisco, CA, USA. 12. Department of Surgery, Vanderbilt University, Nashville, TE, USA. 13. Department of Surgery, Wake Forest School of Medicine, Winston-Salem, NC, USA. 14. Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA. smaithe@emory.edu. 15. Division of Surgical Oncology, Winship Cancer Institute, 1365C Clifton Road NE, 2nd Floor, Atlanta, GA, 30322, USA. smaithe@emory.edu.
Abstract
BACKGROUND: The 7th AJCC T-stage system for adrenocortical carcinoma (ACC), based on size and extra-adrenal invasion, does not adequately stratify patients by survival. Lymphovascular invasion (LVI) is a known poor prognostic factor. We propose a novel T-stage system that incorporates LVI to better risk-stratify patients undergoing resection for ACC. METHOD: Patients undergoing curative-intent resections for ACC from 1993 to 2014 at 13 institutions comprising the US ACC Group were included. Primary outcome was disease-specific survival (DSS). RESULTS: Of the 265 patients with ACC, 149 were included for analysis. The current T-stage system failed to differentiate patients with T2 versus T3 disease (p = 0.10). Presence of LVI was associated with worse DSS versus no LVI (36 mo vs. 168 mo; p = 0.001). After accounting for the individual components of the current T-stage system (size, extra-adrenal invasion), LVI remained a poor prognostic factor on multivariable analysis (hazard ratio 2.14, 95% confidence interval 1.05-4.38, p = 0.04). LVI positivity further stratified patients with T2 and T3 disease (T2: 37 mo vs. median not reached; T3: 36 mo vs. 96 mo; p = 0.03) but did not influence survival in patients with T1 or T4 disease. By incorporating LVI, a new T-stage classification system was created: [T1: ≤ 5 cm, (-)local invasion, (+/-)LVI; T2: > 5 cm, (-)local invasion, (-)LVI OR any size, (+)local invasion, (-)LVI; T3: > 5 cm, (-)local invasion, (+)LVI OR any size, (+)local invasion, (+)LVI; T4: any size, (+)adjacent organ invasion, (+/-)LVI]. Each progressive new T-stage group was associated with worse median DSS (T1: 167 mo; T2: 96 mo; T3: 37 mo; T4: 15 mo; p < 0.001). CONCLUSIONS: Compared with the current T-stage system, the proposed T-stage system, which incorporates LVI, better differentiates T2 and T3 disease and accurately stratifies patients by disease-specific survival. If externally validated, this T-stage classification should be considered for future AJCC staging systems.
BACKGROUND: The 7th AJCC T-stage system for adrenocortical carcinoma (ACC), based on size and extra-adrenal invasion, does not adequately stratify patients by survival. Lymphovascular invasion (LVI) is a known poor prognostic factor. We propose a novel T-stage system that incorporates LVI to better risk-stratify patients undergoing resection for ACC. METHOD:Patients undergoing curative-intent resections for ACC from 1993 to 2014 at 13 institutions comprising the US ACC Group were included. Primary outcome was disease-specific survival (DSS). RESULTS: Of the 265 patients with ACC, 149 were included for analysis. The current T-stage system failed to differentiate patients with T2 versus T3 disease (p = 0.10). Presence of LVI was associated with worse DSS versus no LVI (36 mo vs. 168 mo; p = 0.001). After accounting for the individual components of the current T-stage system (size, extra-adrenal invasion), LVI remained a poor prognostic factor on multivariable analysis (hazard ratio 2.14, 95% confidence interval 1.05-4.38, p = 0.04). LVI positivity further stratified patients with T2 and T3 disease (T2: 37 mo vs. median not reached; T3: 36 mo vs. 96 mo; p = 0.03) but did not influence survival in patients with T1 or T4 disease. By incorporating LVI, a new T-stage classification system was created: [T1: ≤ 5 cm, (-)local invasion, (+/-)LVI; T2: > 5 cm, (-)local invasion, (-)LVI OR any size, (+)local invasion, (-)LVI; T3: > 5 cm, (-)local invasion, (+)LVI OR any size, (+)local invasion, (+)LVI; T4: any size, (+)adjacent organ invasion, (+/-)LVI]. Each progressive new T-stage group was associated with worse median DSS (T1: 167 mo; T2: 96 mo; T3: 37 mo; T4: 15 mo; p < 0.001). CONCLUSIONS: Compared with the current T-stage system, the proposed T-stage system, which incorporates LVI, better differentiates T2 and T3 disease and accurately stratifies patients by disease-specific survival. If externally validated, this T-stage classification should be considered for future AJCC staging systems.
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