Originally published as JCO Early Release 10.1200/JCO.2004.08.173 on April 5 2004

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gunderson, L. L. Articles by Goldberg, R. M. Search for Related Content PubMed PubMed Citation Articles by Gunderson, L. L. Articles by Goldberg, R. M. Social Bookmarking                            What's this?

Impact of T and N Stage and Treatment on Survival and Relapse in Adjuvant Rectal Cancer

A Pooled Analysis

From the Radiation Oncology Department, Mayo Clinic Cancer Center, Scottsdale, AZ; Statistics, Mayo Clinic Cancer Center, Rochester, MN; Radiation Oncology, University of North Carolina, Chapel Hill, NC; Radiation Oncology, Kansas City Community Clinical Oncology Program, Kansas City, MO; Medical Oncology, Allegheny General Hospital, NSABP Operations and Biostatistical Center, Pittsburgh, PA; Abramson Cancer Center at the University of Pennsylvania, Philadelphia; and Oncology, Mayo Clinic Cancer Center, Rochester, MN; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; Radiation Oncology, University of Virginia, Charlottesville, VA; Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston TX; Medical Oncology, St Vincent's Comprehensive Cancer Center, New York, NY; Radiation Oncology, Massachusetts General Hospital, Boston, MA.

Address reprint requests to Leonard L. Gunderson, MD, Mayo Clinic Cancer Center, Scottsdale, 13400 E Shea Blvd, Scottsdale, AZ 85259; e-mail: gunderson.leonard{at}mayo.edu

PURPOSE: To determine survival and relapse rates by T and N stage and treatment method in five randomized phase III North American rectal adjuvant studies.

PATIENTS AND METHODS: Data were pooled from 3,791 eligible patients enrolled onto North Central Cancer Treatment Group (NCCTG) 79-47-51, NCCTG 86-47-51, US Gastrointestinal Intergroup 0114, National Surgical Adjuvant Breast and Bowel Project (NSABP) R01, and NSABP R02. Surgery alone (S) was the treatment arm in 179 patients. The remaining patients received adjuvant treatment as follows: irradiation (RT) alone (n = 281), RT + fluorouracil (FU) ± semustine bolus chemotherapy (CT; n = 779), RT + protracted venous infusion CT (n = 325), RT + FU ± leucovorin or levamisole bolus CT (n = 1,695), or CT alone (n = 532). Five-year follow-up was available in 94% of surviving patients, and 8-year follow-up, in 62%.

RESULTS: Overall (OS) and disease-free survival were dependent on TN stage, NT stage, and treatment method. Even among N2 patients, T substage influenced 5-year OS (T1-2, 67%; T3, 44%; T4, 37%; P < .001). Three risk groups of patients were defined: (1) intermediate (T1-2/N1, T3/N0), (2) moderately high (T1-2/N2, T3/N1, T4/N0), and (3) high (T3/N2, T4/N1, T4/N2). For intermediate-risk patients, those receiving S plus CT had 5-year OS rates of 85% (T1-2/N1) and 84% (T3/N0), which was similar to results with S plus RT plus CT (T1-2/N1, 78% to 83%; T3/N0, 74% to 80%). For moderately high-risk lesions, 5-year OS ranged from 43% to 70% with S plus CT, and 44% to 80% with S plus RT plus CT. For high-risk lesions, 5-year OS ranged from 25% to 45% with S plus CT, and 29% to 57% with S plus RT plus CT.

CONCLUSION: Different treatment strategies may be indicated for intermediate-risk versus moderately high- or high-risk patients based on differential survival rates and rates of relapse. Use of trimodality treatment for all patients with intermediate-risk lesions may be excessive, since S plus CT resulted in 5-year OS of approximately 85%; however, 5-year disease-free survival rates with S plus CT were 78% (T1-2/N1) and 69%(T3/N0), indicating room for improvement.

Oral Presentation at the 39th Annual Meeting of the American Society of Clinical Oncology in Colorectal Cancer Session, Chicago, IL, June 1, 2003.

Authors’ disclosures of potential conflicts of interest are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				A. P. Myers, J. A. Meyerhardt, and L. C. Cantley Getting Knit-PI3Ky: PIK3CA Mutation Status to Direct Multimodality Therapy? Clin. Cancer Res., November 15, 2009; 15(22): 6748 - 6750. [Abstract] [Full Text] [PDF]

				Y. He, L. J. Van't Veer, I. Mikolajewska-Hanclich, M.-L. F. van Velthuysen, E. C.M. Zeestraten, I. D. Nagtegaal, C. J.H. van de Velde, and C. A.M. Marijnen PIK3CA Mutations Predict Local Recurrences in Rectal Cancer Patients Clin. Cancer Res., November 15, 2009; 15(22): 6956 - 6962. [Abstract] [Full Text] [PDF]

				B. D. Minsky Preoperative Treatment for Upper cT3 N0 Rectal Tumors: Is It Required? ASCO Educational Book, January 1, 2009; 2009(1): 204 - 207. [Abstract] [Full Text] [PDF]

				I Zlobec, L Terracciano, L Tornillo, U Gunthert, T Vuong, J R Jass, and A Lugli Role of RHAMM within the hierarchy of well-established prognostic factors in colorectal cancer Gut, October 1, 2008; 57(10): 1413 - 1419. [Abstract] [Full Text] [PDF]

				L. A. Kachnic, T. S. Hong, and D. P. Ryan Rectal Cancer at the Crossroads: The Dilemma of Clinically Staged T3, N0, M0 Disease J. Clin. Oncol., January 20, 2008; 26(3): 350 - 351. [Full Text] [PDF]

				J. G. Guillem, J. A. Diaz-Gonzalez, B. D. Minsky, V. Valentini, S.-Y. Jeong, M. A. Rodriguez-Bigas, C. Coco, R. Leon, J. L. Hernandez-Lizoain, J. J. Aristu, et al. cT3N0 Rectal Cancer: Potential Overtreatment With Preoperative Chemoradiotherapy Is Warranted J. Clin. Oncol., January 20, 2008; 26(3): 368 - 373. [Abstract] [Full Text] [PDF]

				A. B. Benson III New Approaches to Assessing and Treating Early-Stage Colon and Rectal Cancers: Cooperative Group Strategies for Assessing Optimal Approaches in Early-Stage Disease Clin. Cancer Res., November 15, 2007; 13(22): 6913s - 6920s. [Abstract] [Full Text] [PDF]

				C. Aschele and S. Lonardi Multidisciplinary treatment of rectal cancer: medical oncology. Ann. Onc., November 1, 2007; 18(11): 1908 - 1915. [Full Text] [PDF]

				B. D. Minsky Adjuvant Management of Rectal Cancer: The More We Learn, the Less We Know J. Clin. Oncol., October 1, 2007; 25(28): 4339 - 4340. [Full Text] [PDF]

				P. de Heer, E. C. de Bruin, E. Klein-Kranenbarg, R. I.J.M. Aalbers, C. A.M. Marijnen, H. Putter, H. J. de Bont, J. F. Nagelkerke, J. H. J.M. van Krieken, H. W. Verspaget, et al. Caspase-3 Activity Predicts Local Recurrence in Rectal Cancer Clin. Cancer Res., October 1, 2007; 13(19): 5810 - 5815. [Abstract] [Full Text] [PDF]

				P. J. O'Dwyer, S. G. Eckhardt, D. G. Haller, J. Tepper, D. Ahnen, S. Hamilton, A. B. Benson III, M. Rothenberg, N. Petrelli, H.-J. Lenz, et al. Priorities in Colorectal Cancer Research: Recommendations From the Gastrointestinal Scientific Leadership Council of the Coalition of Cancer Cooperative Groups J. Clin. Oncol., June 1, 2007; 25(16): 2313 - 2321. [Abstract] [Full Text] [PDF]

				S. Gill, A. W. Blackstock, and R. M. Goldberg Colorectal Cancer Mayo Clin. Proc., January 1, 2007; 82(1): 114 - 129. [Abstract] [Full Text] [PDF]

				G. C. Harewood, S. Hoecht, W. Hinkelbein, J. W. Cromwell, L. T. Santiago, J. E. Marcet, G. Curigliano, G. Spitaleri, G. Zampino, J.-F. Bosset, et al. Treatment of rectal cancer. N. Engl. J. Med., December 7, 2006; 355(23): 2486 - 2486. [Full Text] [PDF]

				E. C. de Bruin, C. J.H. van de Velde, S. van de Pas, I. D. Nagtegaal, J. H. J.M. van Krieken, M. J.E.M. Gosens, L. T.C. Peltenburg, J. P. Medema, and C. A.M. Marijnen Prognostic value of apoptosis in rectal cancer patients of the dutch total mesorectal excision trial: radiotherapy is redundant in intrinsically high-apoptotic tumors. Clin. Cancer Res., November 1, 2006; 12(21): 6432 - 6436. [Abstract] [Full Text] [PDF]

				G. L. Cascini, A. Avallone, P. Delrio, C. Guida, F. Tatangelo, P. Marone, L. Aloj, F. De Martinis, P. Comella, V. Parisi, et al. 18F-FDG PET Is an Early Predictor of Pathologic Tumor Response to Preoperative Radiochemotherapy in Locally Advanced Rectal Cancer J. Nucl. Med., August 1, 2006; 47(8): 1241 - 1248. [Abstract] [Full Text] [PDF]

				D. P. Ryan, D. Niedzwiecki, D. Hollis, B. E. Mediema, S. Wadler, J. E. Tepper, R. M. Goldberg, and R. J. Mayer Phase I/II Study of Preoperative Oxaliplatin, Fluorouracil, and External-Beam Radiation Therapy in Patients With Locally Advanced Rectal Cancer: Cancer and Leukemia Group B 89901 J. Clin. Oncol., June 1, 2006; 24(16): 2557 - 2562. [Abstract] [Full Text] [PDF]

				I. Chau, G. Brown, D. Cunningham, D. Tait, A. Wotherspoon, A. R. Norman, N. Tebbutt, M. Hill, P. J. Ross, A. Massey, et al. Neoadjuvant Capecitabine and Oxaliplatin Followed by Synchronous Chemoradiation and Total Mesorectal Excision in Magnetic Resonance Imaging-Defined Poor-Risk Rectal Cancer J. Clin. Oncol., February 1, 2006; 24(4): 668 - 674. [Abstract] [Full Text] [PDF]

				D. G. Haller, P. J. Catalano, J. S. Macdonald, M. A. O'Rourke, M. S. Frontiera, D. V. Jackson, and R. J. Mayer Phase III Study of Fluorouracil, Leucovorin, and Levamisole in High-Risk Stage II and III Colon Cancer: Final Report of Intergroup 0089 J. Clin. Oncol., December 1, 2005; 23(34): 8671 - 8678. [Abstract] [Full Text] [PDF]

				H.-C. Kwon, C. H. Moon, S.-H. Kim, H.-J. Choi, H.-S. Lee, M. S. Roh, T.-H. Hwang, J.-S. Kim, and H.-J. Kim Expression of Double-stranded RNA-activated Protein kinase (PKR) and its Prognostic Significance in Lymph Node Negative Rectal Cancer Jpn. J. Clin. Oncol., September 1, 2005; 35(9): 545 - 550. [Abstract] [Full Text] [PDF]

				M. van den Brink, A. M. Stiggelbout, W. B. van den Hout, J. Kievit, E. Klein Kranenbarg, C. A.M. Marijnen, I. D. Nagtegaal, H. J.T. Rutten, T. Wiggers, and C. J.H. van de Velde Clinical Nature and Prognosis of Locally Recurrent Rectal Cancer After Total Mesorectal Excision With or Without Preoperative Radiotherapy J. Clin. Oncol., October 1, 2004; 22(19): 3958 - 3964. [Abstract] [Full Text] [PDF]

				J. E. Tepper Patient Selection, Realism, and Randomized Clinical Trials J. Clin. Oncol., August 15, 2004; 22(16): 3215 - 3217. [Full Text] [PDF]

				C. H. Crane and D. J. Sargent Substitution of Oral Fluoropyrimidines for Infusional Fluorouracil With Radiotherapy: How Much Data Do We Need? J. Clin. Oncol., August 1, 2004; 22(15): 2978 - 2981. [Full Text] [PDF]