title: Neoadjuvant Therapy for Rectal Cancer Affects Lymph Node Yield and Status Without Clear Implications on Outcome: The Case for Eliminating a Metric and Using Preoperative Staging to Guide Therapy.
abstract: Nodal status has long been considered pivotal to oncologic care, staging, and management. This has resulted in the establishment of rudimentary metrics regarding adequate lymph node yield in colon and rectal cancers for accurate cancer staging. In the era of neoadjuvant treatment, the implications of lymph node yield and status on patient outcomes remains unclear.
  
  
  
  This study included 1,680 patients with locally advanced rectal cancer from the NCCN prospective oncology database stratified into 3 groups based on preoperative therapy received: no neoadjuvant therapy, neoadjuvant chemoradiation, and neoadjuvant chemotherapy. Clinicopathologic characteristics and survival were compared between the groups, with univariate and multivariate analyses undertaken.
  
  
  
  The clinicopathologic characteristics demonstrated statistically significant differences and heterogeneity among the 3 groups. The neoadjuvant chemoradiation group demonstrated the statistically lowest median lymph node yield (n=15) compared with 17 and 18 for no-neoadjuvant and neoadjuvant chemotherapy, respectively (P<.0001). Neoadjuvant treatment did impact survival, with chemoradiation demonstrating increased median overall survival of 42.7 compared with 37.3 and 26.6 months for neoadjuvant chemotherapy and no-neoadjuvant therapy, respectively (P<.0001). Patients with a yield of fewer than 12 lymph nodes had improved median overall survival of 43.3 months compared with 36.6 months in patients with 12 or more lymph nodes (P=.009). Multivariate analysis demonstrated that neither node yield nor status were predictors for overall survival.
  
  
  
  This analysis reiterates that nodal yield in rectal cancer is multifactorial, with neoadjuvant therapy being a significant factor. Node yield and status were not significant predictors of overall survival. A nodal metric may not be clinically relevant in the era of neoadjuvant therapy, and guidelines for perioperative therapy may need reconsideration.
authors.affiliation: From Division of Surgical Oncology, The Ohio State University Wexner Medical Center/Arthur G. James Cancer Hospital, Columbus, Ohio; Center for Biostatistics, The Ohio State University Wexner Medical Center, Columbus, Ohio; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois; Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania; City of Hope Comprehensive Cancer Center, Duarte, California; University of Texas MD Anderson Cancer Center, Houston, Texas; Kalispell Regional Healthcare Specialists, Kalispell Regional Healthcare, Kalispell, Montana; Memorial Sloan Kettering Cancer Center, New York, New York; Dana-Farber Cancer Institute, Boston, Massachusetts; and Depaartment of Medicine, Division of Hematology/Oncology, Mayo Clinic Cancer Center, Phoenix, Arizona.
authors.forename: Sherif R Z
authors.initials: SR
authors.lastname: Abdel-Misih
authors.affiliation: From Division of Surgical Oncology, The Ohio State University Wexner Medical Center/Arthur G. James Cancer Hospital, Columbus, Ohio; Center for Biostatistics, The Ohio State University Wexner Medical Center, Columbus, Ohio; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois; Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania; City of Hope Comprehensive Cancer Center, Duarte, California; University of Texas MD Anderson Cancer Center, Houston, Texas; Kalispell Regional Healthcare Specialists, Kalispell Regional Healthcare, Kalispell, Montana; Memorial Sloan Kettering Cancer Center, New York, New York; Dana-Farber Cancer Institute, Boston, Massachusetts; and Depaartment of Medicine, Division of Hematology/Oncology, Mayo Clinic Cancer Center, Phoenix, Arizona.
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.affiliation: From Division of Surgical Oncology, The Ohio State University Wexner Medical Center/Arthur G. James Cancer Hospital, Columbus, Ohio; Center for Biostatistics, The Ohio State University Wexner Medical Center, Columbus, Ohio; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois; Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania; City of Hope Comprehensive Cancer Center, Duarte, California; University of Texas MD Anderson Cancer Center, Houston, Texas; Kalispell Regional Healthcare Specialists, Kalispell Regional Healthcare, Kalispell, Montana; Memorial Sloan Kettering Cancer Center, New York, New York; Dana-Farber Cancer Institute, Boston, Massachusetts; and Depaartment of Medicine, Division of Hematology/Oncology, Mayo Clinic Cancer Center, Phoenix, Arizona.
authors.forename: Al B
authors.initials: AB
authors.lastname: Benson
authors.affiliation: From Division of Surgical Oncology, The Ohio State University Wexner Medical Center/Arthur G. James Cancer Hospital, Columbus, Ohio; Center for Biostatistics, The Ohio State University Wexner Medical Center, Columbus, Ohio; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois; Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania; City of Hope Comprehensive Cancer Center, Duarte, California; University of Texas MD Anderson Cancer Center, Houston, Texas; Kalispell Regional Healthcare Specialists, Kalispell Regional Healthcare, Kalispell, Montana; Memorial Sloan Kettering Cancer Center, New York, New York; Dana-Farber Cancer Institute, Boston, Massachusetts; and Depaartment of Medicine, Division of Hematology/Oncology, Mayo Clinic Cancer Center, Phoenix, Arizona.
authors.forename: Steven
authors.initials: S
authors.lastname: Cohen
authors.affiliation: From Division of Surgical Oncology, The Ohio State University Wexner Medical Center/Arthur G. James Cancer Hospital, Columbus, Ohio; Center for Biostatistics, The Ohio State University Wexner Medical Center, Columbus, Ohio; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois; Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania; City of Hope Comprehensive Cancer Center, Duarte, California; University of Texas MD Anderson Cancer Center, Houston, Texas; Kalispell Regional Healthcare Specialists, Kalispell Regional Healthcare, Kalispell, Montana; Memorial Sloan Kettering Cancer Center, New York, New York; Dana-Farber Cancer Institute, Boston, Massachusetts; and Depaartment of Medicine, Division of Hematology/Oncology, Mayo Clinic Cancer Center, Phoenix, Arizona.
authors.forename: Lily
authors.initials: L
authors.lastname: Lai
authors.affiliation: From Division of Surgical Oncology, The Ohio State University Wexner Medical Center/Arthur G. James Cancer Hospital, Columbus, Ohio; Center for Biostatistics, The Ohio State University Wexner Medical Center, Columbus, Ohio; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois; Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania; City of Hope Comprehensive Cancer Center, Duarte, California; University of Texas MD Anderson Cancer Center, Houston, Texas; Kalispell Regional Healthcare Specialists, Kalispell Regional Healthcare, Kalispell, Montana; Memorial Sloan Kettering Cancer Center, New York, New York; Dana-Farber Cancer Institute, Boston, Massachusetts; and Depaartment of Medicine, Division of Hematology/Oncology, Mayo Clinic Cancer Center, Phoenix, Arizona.
authors.forename: John
authors.initials: J
authors.lastname: Skibber
authors.affiliation: From Division of Surgical Oncology, The Ohio State University Wexner Medical Center/Arthur G. James Cancer Hospital, Columbus, Ohio; Center for Biostatistics, The Ohio State University Wexner Medical Center, Columbus, Ohio; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois; Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania; City of Hope Comprehensive Cancer Center, Duarte, California; University of Texas MD Anderson Cancer Center, Houston, Texas; Kalispell Regional Healthcare Specialists, Kalispell Regional Healthcare, Kalispell, Montana; Memorial Sloan Kettering Cancer Center, New York, New York; Dana-Farber Cancer Institute, Boston, Massachusetts; and Depaartment of Medicine, Division of Hematology/Oncology, Mayo Clinic Cancer Center, Phoenix, Arizona.
authors.forename: Neal
authors.initials: N
authors.lastname: Wilkinson
authors.affiliation: From Division of Surgical Oncology, The Ohio State University Wexner Medical Center/Arthur G. James Cancer Hospital, Columbus, Ohio; Center for Biostatistics, The Ohio State University Wexner Medical Center, Columbus, Ohio; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois; Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania; City of Hope Comprehensive Cancer Center, Duarte, California; University of Texas MD Anderson Cancer Center, Houston, Texas; Kalispell Regional Healthcare Specialists, Kalispell Regional Healthcare, Kalispell, Montana; Memorial Sloan Kettering Cancer Center, New York, New York; Dana-Farber Cancer Institute, Boston, Massachusetts; and Depaartment of Medicine, Division of Hematology/Oncology, Mayo Clinic Cancer Center, Phoenix, Arizona.
authors.forename: Martin
authors.initials: M
authors.lastname: Weiser
authors.affiliation: From Division of Surgical Oncology, The Ohio State University Wexner Medical Center/Arthur G. James Cancer Hospital, Columbus, Ohio; Center for Biostatistics, The Ohio State University Wexner Medical Center, Columbus, Ohio; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois; Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania; City of Hope Comprehensive Cancer Center, Duarte, California; University of Texas MD Anderson Cancer Center, Houston, Texas; Kalispell Regional Healthcare Specialists, Kalispell Regional Healthcare, Kalispell, Montana; Memorial Sloan Kettering Cancer Center, New York, New York; Dana-Farber Cancer Institute, Boston, Massachusetts; and Depaartment of Medicine, Division of Hematology/Oncology, Mayo Clinic Cancer Center, Phoenix, Arizona.
authors.forename: Deborah
authors.initials: D
authors.lastname: Schrag
authors.affiliation: From Division of Surgical Oncology, The Ohio State University Wexner Medical Center/Arthur G. James Cancer Hospital, Columbus, Ohio; Center for Biostatistics, The Ohio State University Wexner Medical Center, Columbus, Ohio; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois; Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania; City of Hope Comprehensive Cancer Center, Duarte, California; University of Texas MD Anderson Cancer Center, Houston, Texas; Kalispell Regional Healthcare Specialists, Kalispell Regional Healthcare, Kalispell, Montana; Memorial Sloan Kettering Cancer Center, New York, New York; Dana-Farber Cancer Institute, Boston, Massachusetts; and Depaartment of Medicine, Division of Hematology/Oncology, Mayo Clinic Cancer Center, Phoenix, Arizona.
authors.forename: Tanios
authors.initials: T
authors.lastname: Bekaii-Saab
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D059186:Chemoradiotherapy, Adjuvant; D017024:Chemotherapy, Adjuvant; D000066491:Clinical Decision-Making / Q000379:methods; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008197:Lymph Node Excision / Q000639:trends*; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy / Q000379:methods*; D009367:Neoplasm Staging; D011300:Preoperative Care / Q000379:methods* / Q000592:standards; D011446:Prospective Studies; D012004:Rectal Neoplasms / Q000401:mortality* / Q000473:pathology / Q000601:surgery*; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult