Pathologic Complete Response of Primary Tumor Following Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancer: Long-term Outcomes and Prognostic Significance of Pathologic Nodal Status (KROG 09-01)

Objective: To investigate long-term outcomes of locally advanced rectal cancer (LARC) patients with postchemoradiotherapy (post-CRT) pathologic complete response of primary tumor (ypT0) and determine prognostic significance of post-CRT pathologic nodal (ypN) status. Background: LARC patients with post-CRT pathologic complete response were suggested to have favorable long-term outcomes, but prognostic significance of ypN status has never been specifically defined in ypT0 patients. Methods: The Korean Radiation Oncology Group collected clinical data for 333 LARC patients with ypT0 following preoperative CRT and curative radical resections between 1993 and 2007. Sphincter preservation surgery and abdominoperineal resection were performed in 283 (85.0%) and 50 (15.0%) patients, respectively. Postoperative chemotherapy was given to 285 (85.6%) patients. Survival was estimated by the Kaplan-Meier method, and the Cox proportional hazard model was used in multivariate analyses. Results: After median follow-up of 43 (range = 14–172) months, 5-year disease-free survival (DFS) was 84.6% and overall survival (OS) was 92.8%. The ypN status was ypT0N0 in 304 (91.3%), ypT0N1 in 22 (6.6%), and ypT0N2 in 7 (2.1%) patients. The ypN status was the most relevant independent prognostic factor for both DFS and OS in ypT0 patients. The 5-year DFS and OS was 88.5% and 94.8% in ypT0N0 patients, and 45.2% and 72.8% in ypT0N+ patients (both, P < 0.001). Conclusions: LARC patients achieving ypT0N0 after preoperative CRT had favorable long-term outcomes, whereas positive ypN status had a poor prognosis even after total regression of primary tumor.

[1]  R. Perez,et al.  Non‐operative management of rectal cancer after neoadjuvant chemoradiation , 2009, The British journal of surgery.

[2]  C. Capirci,et al.  Prognostic value of pathologic complete response after neoadjuvant therapy in locally advanced rectal cancer: long-term analysis of 566 ypCR patients. , 2008, International journal of radiation oncology, biology, physics.

[3]  R. Glynne-Jones,et al.  Complete Clinical Response After Preoperative Chemoradiation in Rectal Cancer: Is a “Wait and See” Policy Justified? , 2008, Diseases of the colon and rectum.

[4]  M. Piérart,et al.  Patients with curative resection of cT3-4 rectal cancer after preoperative radiotherapy or radiochemotherapy: does anybody benefit from adjuvant fluorouracil-based chemotherapy? A trial of the European Organisation for Research and Treatment of Cancer Radiation Oncology Group. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  B. Minsky.  Adjuvant management of rectal cancer: the more we learn, the less we know. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  H. Choi,et al.  Microarray Gene Expression Profiling for Predicting Complete Response to Preoperative Chemoradiotherapy in Patients with Advanced Rectal Cancer , 2007, Diseases of the colon and rectum.

[7]  S. Stryker,et al.  Preoperative chemoradiation for rectal cancer: results of multimodality management and analysis of prognostic factors. , 2007, American journal of surgery.

[8]  R. Glynne-Jones,et al.  Just how useful an endpoint is complete pathological response after neoadjuvant chemoradiation in rectal cancer? , 2006, International journal of radiation oncology, biology, physics.

[9]  P. Johnston.  Prognostic markers of local relapse in rectal cancer: are we any further forward? , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  D. Aust,et al.  Lymph node status and TS gene expression are prognostic markers in stage II/III rectal cancer after neoadjuvant fluorouracil-based chemoradiotherapy. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  J. Guillem,et al.  A Pathologic Complete Response of Rectal Cancer to Preoperative Combined-Modality Therapy Results in Improved Oncological Outcome Compared With Those Who Achieve No Downstaging on the Basis of Preoperative Endorectal Ultrasonography , 2006, Annals of Surgical Oncology.

[12]  G. Kundt,et al.  Postoperative Chemotherapy May Not Be Necessary for Patients With ypN0-Category After Neoadjuvant Chemoradiotherapy of Rectal Cancer , 2006, Diseases of the colon and rectum.

[13]  Tae Hyun Kim,et al.  Is T classification still correlated with lymph node status after preoperative chemoradiotherapy for rectal cancer? , 2006, Cancer.

[14]  V. Valentini,et al.  Long-Term Results After Neoadjuvant Radiochemotherapy for Locally Advanced Resectable Extraperitoneal Rectal Cancer , 2006, Diseases of the colon and rectum.

[15]  M. Guerrieri,et al.  Long‐term results in patients with T2–3 N0 distal rectal cancer undergoing radiotherapy before transanal endoscopic microsurgery , 2005, The British journal of surgery.

[16]  Rainer Fietkau,et al.  Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  M. Mazumdar,et al.  Long-term Oncologic Outcome Following Preoperative Combined Modality Therapy and Total Mesorectal Excision of Locally Advanced Rectal Cancer , 2005, Annals of surgery.

[18]  P. Romestaing,et al.  Preoperative radiotherapy for rectal adenocarcinoma: Which are strong prognostic factors? , 2005, International journal of radiation oncology, biology, physics.

[19]  Shung-Haur Yang,et al.  How Accurate is Magnetic Resonance Imaging in Restaging Rectal Cancer in Patients Receiving Preoperative Combined Chemoradiotherapy? , 2005, Diseases of the colon and rectum.

[20]  A. Morris,et al.  Impact of preoperative radiation for rectal cancer on subsequent lymph node evaluation: a population-based analysis. , 2005, International journal of radiation oncology, biology, physics.

[21]  W. Hohenberger,et al.  Preoperative versus postoperative chemoradiotherapy for rectal cancer. , 2004, The New England journal of medicine.

[22]  Fábio Guilherme Campos,et al.  Operative Versus Nonoperative Treatment for Stage 0 Distal Rectal Cancer Following Chemoradiation Therapy: Long-term Results , 2004, Annals of surgery.

[23]  J. Guillem,et al.  Residual Mesorectal Lymph Node Involvement Following Neoadjuvant Combined-Modality Therapy: Rationale for Radical Resection? , 2004, Annals of Surgical Oncology.

[24]  A. Chan,et al.  Posttreatment TNM staging is a prognostic indicator of survival and recurrence in tethered or fixed rectal carcinoma after preoperative chemotherapy and radiotherapy. , 2003, International journal of radiation oncology, biology, physics.

[25]  D. Rothenberger,et al.  A Pathologic Complete Response to Preoperative Chemoradiation Is Associated With Lower Local Recurrence and Improved Survival in Rectal Cancer Patients Treated by Mesorectal Excision , 2003, Diseases of the colon and rectum.

[26]  V. Valentini,et al.  Does downstaging predict improved outcome after preoperative chemoradiation for extraperitoneal locally advanced rectal cancer? A long-term analysis of 165 patients. , 2002, International journal of radiation oncology, biology, physics.

[27]  S. Larson,et al.  Long-Term Prognostic Significance of Extent of Rectal Cancer Response to Preoperative Radiation and Chemotherapy , 2002, Annals of surgery.

[28]  C. Taylor,et al.  T-Level Downstaging and Complete Pathologic Response After Preoperative Chemoradiation for Advanced Rectal Cancer Result in Decreased Recurrence and Improved Disease-Free Survival , 2002, Diseases of the colon and rectum.

[29]  M. Bonnen,et al.  Long-term results using local excision after preoperative chemoradiation among selected T3 rectal cancer patients. , 2001, International journal of radiation oncology, biology, physics.

[30]  T. Yeatman,et al.  Local Excision of T2 and T3 Rectal Cancers After Downstaging Chemoradiation , 2001, Annals of surgery.

[31]  L. Ellis,et al.  Improved Overall Survival Among Responders to Preoperative Chemoradiation for Locally Advanced Rectal Cancer , 2001, American journal of clinical oncology.

[32]  A. Makris,et al.  Can pathological complete response in the primary tumour following pre-operative pelvic chemoradiotherapy for T3–T4 rectal cancer predict for sterilisation of pelvic lymph nodes, a low risk of local recurrence and the appropriateness of local excision? , 2005, International Journal of Colorectal Disease.

[33]  Cdm Fletcher,et al.  World Health Organization Classification of Tumours , 2002 .

[34]  C. Compton,et al.  Impact of number of nodes retrieved on outcome in patients with rectal cancer. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[35]  L. Aaltonen,et al.  Pathology and genetics of tumours of the digestive system , 2000 .