TY - JOUR
T1 - Association between Surgical Margins Larger Than 1 cm and Overall Survival in Patients with Merkel Cell Carcinoma
AU - Andruska, Neal
AU - Fischer-Valuck, Benjamin W.
AU - Mahapatra, Lily
AU - Brenneman, Randall J.
AU - Gay, Hiram A.
AU - Thorstad, Wade
AU - Fields, Ryan C.
AU - Macarthur, Kelly
AU - Baumann, Brian C.
N1 - Funding Information:
Funding/Support: This study was supported by institutional funds from the Department of Radiation Oncology and the Siteman Cancer Center at Washington University/Barnes Jewish Hospital in St. Louis, Missouri.
Publisher Copyright:
© 2021 American Medical Association. All rights reserved.
PY - 2021/5
Y1 - 2021/5
N2 - Importance: Current recommendations regarding the size of local excision (LE) margins for Merkel cell carcinoma (MCC) have not been well established. Objective: To assess whether larger clinical LE margins and receipt of adjuvant radiotherapy are associated with improvements in overall survival (OS) among patients with localized MCC. Design, Setting, and Participants: This large multicenter retrospective cohort study used records from the National Cancer Database to identify adult patients with localized stage I or stage II MCC who underwent LE between January 1, 2004, and December 31, 2015. Data were analyzed from August 1, 2020, to January 25, 2021. Exposures: Local excision margin size and adjuvant radiotherapy. Main Outcomes and Measures: Overall and net survival were assessed using Cox multivariable regression analysis. Results: A total of 6156 patients with localized MCC (median age at diagnosis, 77 years [range, 27-90 years]; 2500 women [40.6%]). In the multivariable regression analysis, LE clinical margins larger than 1.0 cm were associated with improvements in OS (HR, 0.88; 95% CI, 0.81-0.95; P <.001) compared with margins of 1.0 cm or smaller, regardless of tumor subsite. At 5 years after surgery, LE margins of 1.0 cm or smaller were associated with a net survival of 76.7%, while LE margins larger than 1.0 cm were associated with a net survival of 89.8% (P <.001). Stratification of LE margins into 3 subgroups indicated that LE margins of 1.1 to 2.0 cm (HR, 0.87; 95% CI, 0.76-0.99; P =.047) and larger than 2.0 cm (HR, 0.84; 95% CI, 0.72-0.98; P =.03) were associated with improvements in OS compared with margins of 1.0 cm or smaller. In patients with less aggressive disease (ie, those who were immunocompetent and had tumors =1.0 cm, no lymphovascular invasion, and negative pathologic margins), LE margins larger than 1.0 cm were also associated with improvements in OS (HR, 0.87; 95% CI, 0.78-0.97; P =.01). Among patients who received adjuvant radiotherapy, larger LE margins were associated with improvements in OS (HR, 0.87; 95% CI, 0.76-0.98; P =.03). Receipt of adjuvant radiotherapy was also associated with improvements in OS within the 3 LE margin subgroups. Patients who received adjuvant radiotherapy and had LE margins of 1.0 cm or smaller (HR, 0.81; 95% CI, 0.74-0.89; P <.001) experienced OS that was comparable to that in patients who did not receive adjuvant radiotherapy and had LE margins larger than 1.0 cm (HR, 0.80; 95% CI, 0.71-0.89; P =.87). Conclusions and Relevance: In this study, LE clinical margins larger than 1.0 cm were associated with improvements in OS, and these improvements were independent of tumor subsite, receipt of adjuvant radiotherapy, positive pathologic margins, or adverse pathologic features for stage I to stage II MCC. Patients with LE margins of 1.0 cm or smaller who received adjuvant radiotherapy experienced OS that was similar to that of patients with larger LE margins who did not receive radiotherapy. The combination of LE clinical margins larger than 1.0 cm and adjuvant radiotherapy was associated with the highest OS.
AB - Importance: Current recommendations regarding the size of local excision (LE) margins for Merkel cell carcinoma (MCC) have not been well established. Objective: To assess whether larger clinical LE margins and receipt of adjuvant radiotherapy are associated with improvements in overall survival (OS) among patients with localized MCC. Design, Setting, and Participants: This large multicenter retrospective cohort study used records from the National Cancer Database to identify adult patients with localized stage I or stage II MCC who underwent LE between January 1, 2004, and December 31, 2015. Data were analyzed from August 1, 2020, to January 25, 2021. Exposures: Local excision margin size and adjuvant radiotherapy. Main Outcomes and Measures: Overall and net survival were assessed using Cox multivariable regression analysis. Results: A total of 6156 patients with localized MCC (median age at diagnosis, 77 years [range, 27-90 years]; 2500 women [40.6%]). In the multivariable regression analysis, LE clinical margins larger than 1.0 cm were associated with improvements in OS (HR, 0.88; 95% CI, 0.81-0.95; P <.001) compared with margins of 1.0 cm or smaller, regardless of tumor subsite. At 5 years after surgery, LE margins of 1.0 cm or smaller were associated with a net survival of 76.7%, while LE margins larger than 1.0 cm were associated with a net survival of 89.8% (P <.001). Stratification of LE margins into 3 subgroups indicated that LE margins of 1.1 to 2.0 cm (HR, 0.87; 95% CI, 0.76-0.99; P =.047) and larger than 2.0 cm (HR, 0.84; 95% CI, 0.72-0.98; P =.03) were associated with improvements in OS compared with margins of 1.0 cm or smaller. In patients with less aggressive disease (ie, those who were immunocompetent and had tumors =1.0 cm, no lymphovascular invasion, and negative pathologic margins), LE margins larger than 1.0 cm were also associated with improvements in OS (HR, 0.87; 95% CI, 0.78-0.97; P =.01). Among patients who received adjuvant radiotherapy, larger LE margins were associated with improvements in OS (HR, 0.87; 95% CI, 0.76-0.98; P =.03). Receipt of adjuvant radiotherapy was also associated with improvements in OS within the 3 LE margin subgroups. Patients who received adjuvant radiotherapy and had LE margins of 1.0 cm or smaller (HR, 0.81; 95% CI, 0.74-0.89; P <.001) experienced OS that was comparable to that in patients who did not receive adjuvant radiotherapy and had LE margins larger than 1.0 cm (HR, 0.80; 95% CI, 0.71-0.89; P =.87). Conclusions and Relevance: In this study, LE clinical margins larger than 1.0 cm were associated with improvements in OS, and these improvements were independent of tumor subsite, receipt of adjuvant radiotherapy, positive pathologic margins, or adverse pathologic features for stage I to stage II MCC. Patients with LE margins of 1.0 cm or smaller who received adjuvant radiotherapy experienced OS that was similar to that of patients with larger LE margins who did not receive radiotherapy. The combination of LE clinical margins larger than 1.0 cm and adjuvant radiotherapy was associated with the highest OS.
UR - http://www.scopus.com/inward/record.url?scp=85103346333&partnerID=8YFLogxK
U2 - 10.1001/jamadermatol.2021.0247
DO - 10.1001/jamadermatol.2021.0247
M3 - Article
C2 - 33760021
AN - SCOPUS:85103346333
SN - 2168-6068
VL - 157
SP - 540
EP - 548
JO - JAMA Dermatology
JF - JAMA Dermatology
IS - 5
ER -