Adrienne B Shannon1, Richard J Straker2, Michael J Carr3,4, James Sun5, Karenia Landa6, Kirsten Baecher7, Kevin Lynch8, Harrison G Bartels9, Robyn Panchaud4,10, Luke J Keele2, Michael C Lowe7, Craig L Slingluff8, Mark J Jameson9, Kenneth Y Tsai4,10, Mark B Faries11, Georgia M Beasley6, Vernon K Sondak3,4, Giorgos C Karakousis2, Jonathan S Zager3,4, John T Miura2. 1. Division of Endocrine and Oncologic Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. Adrienne.shannon@pennmedicine.upenn.edu. 2. Division of Endocrine and Oncologic Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. 3. Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA. 4. Department of Oncologic Sciences, University of South Florida Morsani College of Medicine, Tampa, FL, USA. 5. Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH, USA. 6. Division of Surgical Oncology, Department of Surgery, Duke University Medical Center, Durham, NC, USA. 7. Division of Surgical Oncology, Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA. 8. Division of Breast and Melanoma Surgery, Department of Surgery, University of Virginia, Charlottesville, VA, USA. 9. Division of Head and Neck Surgical Oncology, Department of Otolaryngology, University of Virginia, Charlottesville, VA, USA. 10. Department of Pathology, Moffitt Cancer Center, Tampa, FL, USA. 11. Division of Surgical Oncology, Cedars-Sinai Medical Center, The Angeles Clinic and Research Institute, Los Angeles, CA, USA.
Abstract
BACKGROUND: Merkel cell carcinoma (MCC) is a rare cutaneous malignancy for which factors predictive of disease-specific survival (DSS) are poorly defined. METHODS: Patients from six centers (2005-2020) with clinical stage I-II MCC who underwent sentinel lymph node (SLN) biopsy were included. Factors associated with DSS were identified using competing-risks regression analysis. Risk-score modeling was established using competing-risks regression on a training dataset and internally validated by point assignment to variables. RESULTS: Of 604 patients, 474 (78.5%) and 128 (21.2%) patients had clinical stage I and II disease, respectively, and 189 (31.3%) had SLN metastases. The 5-year DSS rate was 81.8% with a median follow-up of 31 months. Prognostic factors associated with worse DSS included increasing age (hazard ratio [HR] 1.03, p = 0.046), male sex (HR 3.21, p = 0.021), immune compromise (HR 2.46, p = 0.013), presence of microsatellites (HR 2.65, p = 0.041), and regional nodal involvement (1 node: HR 2.48, p = 0.039; ≥2 nodes: HR 2.95, p = 0.026). An internally validated, risk-score model incorporating all of these factors was developed with good performance (AUC 0.738). Patients with ≤ 4.00 and > 4.00 points had 5-year DSS rates of 89.4% and 67.2%, respectively. Five-year DSS for pathologic stage I/II patients with > 4.00 points (n = 49) was 79.8% and for pathologic stage III patients with ≤ 4.00 points (n = 62) was 90.3%. CONCLUSIONS: A risk-score model, including patient and tumor factors, based on DSS improves prognostic assessment of patients with clinically localized MCC. This may inform surveillance strategies and patient selection for adjuvant therapy trials.
BACKGROUND: Merkel cell carcinoma (MCC) is a rare cutaneous malignancy for which factors predictive of disease-specific survival (DSS) are poorly defined. METHODS: Patients from six centers (2005-2020) with clinical stage I-II MCC who underwent sentinel lymph node (SLN) biopsy were included. Factors associated with DSS were identified using competing-risks regression analysis. Risk-score modeling was established using competing-risks regression on a training dataset and internally validated by point assignment to variables. RESULTS: Of 604 patients, 474 (78.5%) and 128 (21.2%) patients had clinical stage I and II disease, respectively, and 189 (31.3%) had SLN metastases. The 5-year DSS rate was 81.8% with a median follow-up of 31 months. Prognostic factors associated with worse DSS included increasing age (hazard ratio [HR] 1.03, p = 0.046), male sex (HR 3.21, p = 0.021), immune compromise (HR 2.46, p = 0.013), presence of microsatellites (HR 2.65, p = 0.041), and regional nodal involvement (1 node: HR 2.48, p = 0.039; ≥2 nodes: HR 2.95, p = 0.026). An internally validated, risk-score model incorporating all of these factors was developed with good performance (AUC 0.738). Patients with ≤ 4.00 and > 4.00 points had 5-year DSS rates of 89.4% and 67.2%, respectively. Five-year DSS for pathologic stage I/II patients with > 4.00 points (n = 49) was 79.8% and for pathologic stage III patients with ≤ 4.00 points (n = 62) was 90.3%. CONCLUSIONS: A risk-score model, including patient and tumor factors, based on DSS improves prognostic assessment of patients with clinically localized MCC. This may inform surveillance strategies and patient selection for adjuvant therapy trials.
Authors: Franz O Smith; Binglin Yue; Suroosh S Marzban; Brooke L Walls; Michael Carr; Ryan S Jackson; Christopher A Puleo; Tapan Padhya; C Wayne Cruse; Ricardo J Gonzalez; Amod A Sarnaik; Michael J Schell; Ronald C DeConti; Jane L Messina; Vernon K Sondak; Jonathan S Zager Journal: Cancer Date: 2015-06-02 Impact factor: 6.860
Authors: C R Farley; M C Perez; S J Soelling; K A Delman; A Harit; E J Wuthrick; J L Messina; V K Sondak; J S Zager; M C Lowe Journal: Ann Surg Oncol Date: 2020-02-26 Impact factor: 5.344
Authors: Cathy S Lim; Deborah Whalley; Lauren E Haydu; Rajmohan Murali; Jill Tippett; John F Thompson; George Hruby; Richard A Scolyer Journal: Ann Surg Oncol Date: 2012-07-21 Impact factor: 5.344
Authors: Vishwajith Sridharan; Vinayak Muralidhar; Danielle N Margalit; Roy B Tishler; James A DeCaprio; Manisha Thakuria; Guilherme Rabinowits; Jonathan D Schoenfeld Journal: J Natl Compr Canc Netw Date: 2016-10 Impact factor: 11.908
Authors: Juan A Santamaria-Barria; Genevieve M Boland; Beow Y Yeap; Valentina Nardi; Dora Dias-Santagata; James C Cusack Journal: Ann Surg Oncol Date: 2012-12-01 Impact factor: 5.344
Authors: Timothy L Fitzgerald; Samuel Dennis; Swapnil D Kachare; Nasreen A Vohra; Jan H Wong; Emmanuel E Zervos Journal: Am Surg Date: 2015-08 Impact factor: 0.688
Authors: Kelly G Paulson; Song Youn Park; Natalie A Vandeven; Kristina Lachance; Hannah Thomas; Aude G Chapuis; Kelly L Harms; John A Thompson; Shailender Bhatia; Andreas Stang; Paul Nghiem Journal: J Am Acad Dermatol Date: 2017-11-02 Impact factor: 11.527
Authors: Kelly L Harms; Mark A Healy; Paul Nghiem; Arthur J Sober; Timothy M Johnson; Christopher K Bichakjian; Sandra L Wong Journal: Ann Surg Oncol Date: 2016-05-19 Impact factor: 5.344