0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Article |

Improvement of Survival With Response to Neoadjuvant Radiation Therapy for Rectal Cancer FREE

Eric T. Castaldo, MD, MPH; Alexander A. Parikh, MD; C. Wright Pinson, MD, MBA; Irene D. Feurer, PhD; Nipun B. Merchant, MD
[+] Author Affiliations

Author Affiliations: Divisions of Hepatobiliary Surgery and Liver Transplantation (Drs Castaldo, Pinson, and Feurer) and Surgical Oncology (Drs Parikh and Merchant), Department of Surgery, and Department of Biostatistics (Dr Feurer), Vanderbilt University Medical Center, Nashville, Tennessee.


Arch Surg. 2009;144(2):129-134. doi:10.1001/archsurg.2008.549.
Text Size: A A A
Published online

Objectives  To determine whether patients with a complete or near-complete response to neoadjuvant radiation therapy (XRT) have improved survival compared with those with less of a response and to compare survival between patients with disease downstaged after neoadjuvant XRT and patients with stage I disease undergoing resection alone.

Design, Setting, and Patients  Retrospective cohort of 10 971 patients (3760 patients with neoadjuvant XRT; 7211 with stage I disease with resection alone) from the Surveillance, Epidemiology, and End Results registry using data from January 1, 1994, through December 31, 2003.

Main Outcome Measures  Overall survival and disease-specific survival (DSS) of patients undergoing resection for nonmetastatic rectal adenocarcinoma receiving neoadjuvant XRT and patients with stage I disease undergoing surgical resection alone.

Results  The 5-year DSS and overall survival were 94% and 82%, respectively, for responders to neoadjuvant XRT, 78% and 60%, respectively, for nonresponders, and 97% and 79%, respectively, for patients with stage I disease undergoing resection alone. Responders had improved DSS (P < .001) and overall survival (P < .001) compared with nonresponders by Cox regression. Patients with stage I disease undergoing resection alone had improved DSS (P = .01) but not overall survival (P = .89) compared with XRT responders.

Conclusions  Patients with rectal adenocarcinoma downstaged after neoadjuvant XRT have improved survival compared with nonresponders. While DSS is excellent for responders to neoadjuvant XRT, it did not equal the DSS of patients with stage I disease undergoing resection alone.

Figures in this Article

Colorectal cancer is the third most common cancer and the third leading cause of cancer-related mortality in the United States, and rectal cancer composes about 30% of these cases.1 In particular, patients with T3 or node-positive rectal adenocarcinoma (stage II or III) are at high risk for local recurrence and distant metastasis.

The treatment of rectal cancer has evolved significantly during the past 25 years. In the 1980s, the National Surgical Adjuvant Breast and Bowel Protocol R01 trial2 and the Gastrointestinal Tumor Study Group Protocol 7175 trial3 demonstrated the benefit of adjuvant chemotherapy and radiation therapy (XRT) for local control and/or survival in patients with stage II and III rectal cancer.

The utility of neoadjuvant chemoradiation therapy has emerged as a promising treatment for rectal cancer. Prospective randomized trials have demonstrated improved local control and survival with neoadjuvant XRT compared with surgical resection alone for rectal cancer.47 Recently, the German Rectal Cancer Study Group8 showed that neoadjuvant chemoradiation therapy is less toxic, enhances sphincter preservation, and results in significant downstaging of rectal tumors compared with adjuvant chemoradiation therapy. This trial also demonstrated that neoadjuvant chemoradiation therapy improves local control of rectal cancer, but it did not show a survival benefit compared with patients who received adjuvant chemoradiation therapy. Additionally, a recent meta-analysis9 concluded that neoadjuvant XRT improved overall survival (OS) and disease-specific survival (DSS) as well as local recurrence compared with resection alone.

Other studies have shown similar benefits of neoadjuvant chemoradiation therapy, and complete response rates of 10% to 30% have been reported.1012 It is becoming more evident that neoadjuvant XRT, with or without chemotherapy, is becoming the standard treatment approach for stage II and III rectal adenocarcinoma.

We and others have shown in single-institution studies that a clinically significant response to neoadjuvant therapy for rectal cancer improves outcomes in these patients.1315 Other studies have also assessed the differences in survival based on morphologic patterns and response rates to neoadjuvant therapy, indicating improved survival for patients with strong clinical response.12,16

To our knowledge, there has been no population-based study to date that has noted the effect of pathologic response to neoadjuvant XRT on survival. The primary aim of this study was to determine, in a large population-based database, whether patients with a good clinical response to neoadjuvant XRT for rectal adenocarcinoma have improved survival compared with patients who do not have a good response. The secondary aim was to then determine whether patients who have disease successfully downstaged to stage 0 or I by neoadjuvant XRT prior to surgical resection have survival similar to that in patients with stage I disease who undergo resection alone.

Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) registry (SEER-17, 1973-2003 data set) of the National Cancer Institute (November 2005 edition) using SEER*Stat software version 6.2.4 (Surveillance Research Program, National Cancer Institute, Bethesda, Maryland).17 The SEER program collects and publishes cancer incidence and survival data from geographically defined, population-based cancer registries covering approximately 26% of the US population.18 The data contained in the SEER program are deidentified and publicly available. The populations captured in the data are considered representative of the Unites States as a whole.

The study population consisted of all patients with adenocarcinoma of the rectum who received neoadjuvant XRT and were diagnosed as having American Joint Committee on Cancer19 stage 0, I, II, or III on pathologic analysis after surgical resection from January 1, 1994, through December 31, 2003. Exclusion criteria consisted of the following: patients with a second primary malignant neoplasm, patients who received any form of radiation other than neoadjuvant external-beam XRT, patients who did not undergo operative resection, patients who underwent local excisions only, and patients with incomplete data. For the secondary analysis, all of the patients with complete data who were diagnosed with stage I disease and received surgical resection alone were extracted, excluding those who underwent local excisions only. Other collected information included age, race, sex, year of diagnosis, tumor histological findings, tumor grade, surgical procedure, mortal status, and cause of death. Follow-up time was calculated from the time of diagnosis until the last contact, the date of death, or the date used as a cutoff in the database.

Preoperative and preradiation clinical stages are not available in this database. Neoadjuvant XRT is recommended for patients with preoperatively diagnosed stage II or III rectal cancer. Therefore, patients were classified as responders to neoadjuvant XRT if their stage at pathologic evaluation after surgical resection was 0 or I, indicating a clinical downstaging of disease. If patients had stage II or III disease on pathologic analysis, they were considered nonresponders to neoadjuvant XRT. Although some downstaging of disease may have occurred in these patients, this was not considered to be a significant clinical response for comparison in this study.

Information on local or distant recurrence is not provided in this database, so disease-free survival cannot be determined. Patient cause of death is reported, therefore DSS (death due to rectal cancer) and OS can be determined. Statistical analysis for DSS and OS were accomplished via Kaplan-Meier methods and the log-rank test. Cox proportional hazard regression was used to adjust for the effects of being aged 60 years or older, race, sex, and tumor grade to determine whether patients with a good response to neoadjuvant XRT have improved DSS and/or OS compared with those who do not respond to neoadjuvant XRT. The secondary analysis, comparing DSS and OS between patients with a good response to neoadjuvant XRT (stage 0 or I) and patients with stage I disease who underwent radical resection alone (ie, no local excision), was carried out in a similar fashion.

The SEER data are fully deidentified before release, so the study was exempt from formal review by the Vanderbilt University Institutional Review Board. We used SPSS statistical software version 14.0 (SPSS Inc, Chicago, Illinois) for statistical evaluation, with P < .05 taken to be statistically significant.

A total of 10 971 patients were included in the study (Table 1). There were 3760 patients who received neoadjuvant XRT for rectal cancer; 21% (n = 792) were responders (pathologic stage 0 or I) and 79% (n = 2968) were nonresponders (pathologic stage II or III) at the time of surgical resection. There were 7211 patients with stage I disease who underwent surgical resection alone. The median follow-up time for the entire cohort was 31 months (range, 0-119 months). There were 9084 patients alive at last follow-up. Death due to rectal cancer was reported in 493 patients (4%), and 1394 deaths (13%) were due to other causes.

Table Graphic Jump LocationTable 1. Demographic Characteristics of Patients With Rectal Cancer Grouped by Radiation Therapy

Figure 1A shows a Kaplan-Meier DSS curve comparing responders to neoadjuvant XRT against nonresponders. The 3- and 5-year DSSs for responders to neoadjuvant XRT were 97% and 94%, respectively. The 3- and 5-year DSSs for nonresponders were 86% and 78%, respectively. These differences were statistically significant (P < .001). The Cox regression model confirmed that responders had improved DSS compared with nonresponders (hazard ratio [HR] = 0.29; 95% confidence interval [CI], 0.19-0.43; P < .001). Cox regression also demonstrated worse DSS for patients aged 60 years or older (HR = 1.44; 95% CI, 1.15-1.90; P = .001), women (HR = 1.25; 95% CI, 1.00-1.56; P = .05), African American patients (HR = 1.83; 95% CI, 1.29-2.62; P < .001), and patients with poorly differentiated or anaplastic tumor grades (HR = 2.69; 95% CI, 1.54-4.71; P = .001). The results of Cox regression for DSS are summarized in Table 2.

Place holder to copy figure label and caption
Figure 1.

Kaplan-Meier curves. A, Kaplan-Meier curve demonstrating improved disease-specific survival (P < .001) for patients with a good response to radiation therapy compared with those who fail to respond. The median survival was not reached in either group. B, Kaplan-Meier curve demonstrating improved overall survival for patients who respond to neoadjuvant radiation therapy compared with nonresponders (P < .001). The median survival was not reached for responders and was 7 years for nonresponders.

Graphic Jump Location
Table Graphic Jump LocationTable 2. Cox Regression of Disease-Specific and Overall Survivala

The Kaplan-Meier OS curve for responders and nonresponders to XRT is seen in Figure 1B. The 3- and 5-year OSs for responders were 91% and 82%, respectively, and the 3- and 5-year OSs for nonresponders were 74% and 60%, respectively (P < .001). Cox regression confirmed that responders had improved OS compared with nonresponders (HR = 0.41; 95% CI, 0.32-0.51; P < .001). Worse OS was demonstrated for patients aged 60 years or older (HR = 1.79; 95% CI, 1.53-2.09; P < .001), African American patients (HR = 1.44; 95% CI, 1.10-1.88; P = .01), and patients with poor or anaplastic tumor grades (HR = 2.27; 95% CI, 1.56-3.30; P < .001). The results of the Cox regression model for OS are summarized in Table 2.

Figure 2A shows a Kaplan-Meier DSS curve comparing responders to neoadjuvant XRT with patients with stage I disease undergoing surgical resection alone. The 3- and 5-year DSSs of patients with stage I disease undergoing resection alone were 98% and 97%, respectively (responders had a 3-year DSS of 97% and a 5-year DSS of 94%). The DSS was significantly better for these patients compared with responders to neoadjuvant XRT (P = .01). Cox regression demonstrated worse DSS for responders to neoadjuvant XRT compared with patients with stage I disease undergoing resection alone (HR = 1.82; 95% CI, 1.19-2.77; P = .01). Cox regression showed worse DSS for patients aged 60 years or older (HR = 2.04; 95% CI, 1.42-2.93; P < .001). The results from the Cox regression model are summarized in Table 3.

Place holder to copy figure label and caption
Figure 2.

Kaplan-Meier curves. A, Kaplan-Meier curve demonstrating improved disease-specific survival (P = .01) for patients with stage I disease undergoing resection alone compared with patients who respond to neoadjuvant radiation therapy and have disease downstaged to stage 0 or I. The median survival was not reached for either group. B, Kaplan-Meier curve demonstrating similar overall survival in patients who are responders to neoadjuvant radiation therapy compared with patients with stage I rectal cancer undergoing resection alone. The curves were statistically significantly different (P = .04); however, the curves cross, giving the log-rank test low power to detect a true difference. The median survival was not reached for either group.

Graphic Jump Location
Table Graphic Jump LocationTable 3. Cox Regression of Disease-Specific and Overall Survival of Responders to Neoadjuvant Radiation Therapy vs Patients With Stage I Disease Undergoing Resection Alonea

A Kaplan-Meier OS curve comparing responders to neoadjuvant XRT with patients with stage I disease undergoing resection alone can be seen in Figure 2B. The 3- and 5-year OSs of patients with stage I disease undergoing resection alone were 88% and 79%, respectively (responders had a 3-year OS of 91% and a 5-year OS of 82%). This difference was statistically significant (P = .04). However, OS was not statistically significant via Cox regression (HR = 0.89; 95% CI, 0.71-1.12; P = .89). Cox regression (Table 3) demonstrated worse OS for patients aged 60 years or older (HR = 3.96; 95% CI, 3.30-4.76; P < .001) and for patients with moderately differentiated tumors (HR = 1.30; 95% CI, 1.08-1.55; P = .01) but improved OS for women (HR = 0.79; 95% CI, 0.71-0.88; P < .001).

Review of a large cohort of patients in this study demonstrates that patients who respond to neoadjuvant XRT for rectal adenocarcinoma and have disease downstaged to American Joint Committee on Cancer stage 0 or I on pathologic analysis after surgical resection have improved DSS and OS compared with patients with disease that remains at stage II or III after neoadjuvant therapy.

This study from a large population database confirms findings in recent single-institution studies showing that complete or near-complete responders to neoadjuvant XRT have improved survival. Garcíia-Aguilar et al14 demonstrated a 95% 5-year OS in patients with a complete pathologic response to neoadjuvant chemoradiation therapy. Guillem et al20 also demonstrated that patients with a greater than 95% response rate to neoadjuvant therapy had a 93% 5-year OS and had significantly improved OS compared with patients with a less than 95% response rate. We have previously shown that patients with disease downstaged to stage 0 or I after neoadjuvant chemoradiation therapy had an 88% 5-year DSS at a median follow-up of 62 months, whereas patients with a complete pathologic response had a 100% 5-year OS and a 100% 5-year DSS.13

The results of this study also show that patients with disease downstaged to stage 0 or I have an excellent long-term DSS (approximately 94% at 5 years). Despite the excellent outcomes in these patients, DSS in responders still remained significantly less than that in patients with stage I disease who do not require neoadjuvant XRT (5-year DSS of approximately 97%). This statistical significance is likely owing to the very large number of patients (n = 7211) in the group with stage I disease undergoing resection alone. When comparing the OS, however, the outcomes are similar in each group. This indicates that patients with stage II or III rectal cancer who have a complete or near-complete response to neoadjuvant XRT can achieve survival rates similar to that of patients who present with stage I disease.

Furthermore, as others have shown, responders to neoadjuvant XRT may undergo local excision and still achieve excellent long-term outcomes.21,22 Carrying this concept one step further, Habr-Gama et al23,24 have shown that patients who have a complete clinical response to neoadjuvant XRT may be observed without surgical resection and maintain excellent outcomes. In a cohort of 99 patients managed nonoperatively after a complete clinical response to neoadjuvant chemoradiation therapy sustained for at least 12 months, they demonstrated a 5-year OS of 93% and a disease-free survival of 85%. Of the 5% of these patients who had an isolated local recurrence, all cases were able to be salvaged with surgical intervention.24

Rates of pathologic downstaging of rectal cancer vary from 19% to 61%.15,25 In this study, the rate of pathologic downstaging to stage 0 or I was 21% of patients who received neoadjuvant XRT. This finding is similar to a study by Shia et al16 in which 19% of their patients without stage IV disease had their disease downstaged to stage 0 or I. This finding is also similar to several other studies in which complete pathologic response rates ranged from 13% to 18%.13,14,20,25

Information on patients receiving preoperative or postoperative chemotherapy is not included in the SEER database; therefore, the effect of chemotherapy with XRT in the neoadjuvant setting or its overall effect on OS and DSS cannot be addressed. However, in the United States, standard neoadjuvant therapy generally includes fluorouracil-based chemotherapy with concomitant external-beam XRT (4500-5040 cGy [the conversion of centigray to rad is 1:1]), followed by surgical resection 4 to 8 weeks later, and then followed by 4 to 6 cycles of additional adjuvant fluorouracil-based chemotherapy. Therefore, an assumption has to be made that patients who received XRT would have received chemotherapy also. However, standard neoadjuvant treatment for rectal cancer in Europe involves high-fraction, short-course XRT followed by surgical resection after a short interval (5-14 days) and no subsequent chemotherapy. This treatment regimen has been shown to improve survival compared with surgery alone.5,26 Therefore, the role of chemotherapy in this analysis may not have a significant effect on outcomes in these patients. Although the use of adjuvant chemotherapy in this population is unknown, the similarity of outcomes of responders to neoadjuvant therapy (with stage 0 or I disease) and outcomes of patients with stage I disease undergoing resection alone, who do not require additional chemotherapy, calls into question the need for further adjuvant chemotherapy among those patients with a complete or near-complete pathologic response after neoadjuvant chemoradiation.

Preoperative staging of rectal cancer remains difficult. At best, transrectal ultrasonography shows 80% to 90% accuracy for T category and 70% to 75% for N category.2730 Preoperative staging information is unavailable in the SEER registry. Because neoadjuvant therapy is indicated in stage II and III rectal cancer, patients in the database who received neoadjuvant XRT were therefore assumed to have stage II or III disease at their initial diagnosis. Because it is difficult to assess minimal response rates (ie, stage III downstaged to stage II) even in a prospective fashion, responders to neoadjuvant XRT were considered only if the pathologic specimen was at stage 0 or I at the time of surgical resection. Patients with disease that remained at stage II or III on pathologic staging at the time of surgical resection after neoadjuvant XRT were assumed to have minimal or no response. Because some patients may have had neoadjuvant XRT and received only a local excision, only patients undergoing abdominoperineal resection or low anterior resection were included in this study.

Several studies have suggested that African American patients have higher mortality rates from colorectal cancer compared with white patients. We have previously shown significantly worse median survival for African American patients compared with white patients in both a university setting and a city hospital setting.31 Our results confirm the increased risk of death due to rectal cancer for African American patients even when adjusting for response to radiation, age, sex, and tumor grade in our Cox regression model. There are several reasons that have been investigated to explain these differences. They include such factors as the following: access to care, socioeconomic status, difference in screening, more progressive disease at diagnosis, genetic differences, and therapeutic differences32,33; however, these could not be addressed from the SEER database.

Other limitations of this study include the lack of information on the dose and/or completion of XRT. Inherent in database studies are the potential pitfalls of data quality. The SEER program is considered the standard for data quality around the world and is the authoritative source for cancer statistics in the United States. Furthermore, in an effort to be assured that the tumor staging data were accurate, a random sample of 1000 patients was validated. The primary tumor characteristics were obtained and converted into the TNM staging system, and these results were cross-referenced to the stage of disease as listed in the SEER program. There was a 100% correlation. Additionally, it should be noted that the median follow-up in this study is only 31 months. However, in a prospective study, neoadjuvant XRT previously demonstrated decreased local failure rates (2.4%) at 2 years.7

We have shown in a large population database that patients with rectal cancer who have a complete or near-complete response to neoadjuvant XRT have improved DSS and OS compared with those with a minimal response. Furthermore, the survival of patients with an excellent response to neoadjuvant XRT is similar to that in patients with stage I rectal cancer undergoing resection alone.

Correspondence: Nipun B. Merchant, MD, Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, 2220 Pierce Ave, Nashville, TN 37232-6860 (nipun.merchant@vanderbilt.edu).

Accepted for Publication: January 5, 2008.

Author Contributions:Study concept and design: Castaldo, Parikh, Pinson, Feurer, and Merchant. Acquisition of data: Castaldo. Analysis and interpretation of data: Castaldo and Feurer. Drafting of the manuscript: Castaldo. Critical revision of the manuscript for important intellectual content: Parikh, Pinson, Feurer, and Merchant. Statistical analysis: Castaldo and Feurer. Administrative, technical, and material support: Parikh, Pinson, and Merchant. Study supervision: Parikh, Pinson, and Merchant.

Financial Disclosure: None reported.

Funding/Support: This work was supported in part by an educational grant from Novartis Pharmaceuticals, Inc.

Previous Presentation: This paper was presented in part at the 92nd Annual Clinical Congress of the American College of Surgeons; October 11, 2006; Chicago, Illinois.

National Cancer Institute, A Snapshot of Colorectal Cancer.  Bethesda, MD National Cancer Institute2006;
Fisher  BWolmark  NRockette  H  et al.  Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01. J Natl Cancer Inst 1988;80 (1) 21- 29
PubMed Link to Article
Gastrointestinal Tumor Study Group, Prolongation of the disease-free interval in surgically treated rectal carcinoma. N Engl J Med 1985;312 (23) 1465- 1472
PubMed Link to Article
Stockholm Colorectal Cancer Study Group, Randomized study on preoperative radiotherapy in rectal carcinoma. Ann Surg Oncol 1996;3 (5) 423- 430
PubMed Link to Article
Swedish Rectal Cancer Trial, Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med 1997;336 (14) 980- 987
PubMed Link to Article
Cedermark  BJohansson  HRutqvist  LEWilking  NStockholm Colorectal Cancer Study Group, The Stockholm I trial of preoperative short term radiotherapy in operable rectal carcinoma: a prospective randomized trial. Cancer 1995;75 (9) 2269- 2275
PubMed Link to Article
Kapiteijn  EMarijnen  CANagtegaal  ID  et al. Dutch Colorectal Cancer Group, Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 2001;345 (9) 638- 646
PubMed Link to Article
Sauer  RBecker  HHohenberger  W  et al. German Rectal Cancer Study Group, Preoperative vs postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004;351 (17) 1731- 1740
PubMed Link to Article
Cammà  CGiunta  MFiorica  FPagliaro  LCraxì  ACottone  M Preoperative radiotherapy for resectable rectal cancer: a meta-analysis. JAMA 2000;284 (8) 1008- 1015
PubMed Link to Article
Mohiuddin  MWinter  KMitchell  E  et al. Radiation Therapy Oncology Group Trial 0012, Randomized phase II study of neoadjuvant combined-modality chemoradiation for distal rectal cancer: Radiation Therapy Oncology Group Trial 0012. J Clin Oncol 2006;24 (4) 650- 655
PubMed Link to Article
Rullier  EGoffre  BBonnel  CZerbib  FCaudry  MSaric  J Preoperative radiochemotherapy and sphincter-saving resection for T3 carcinomas of the lower third of the rectum. Ann Surg 2001;234 (5) 633- 640
PubMed Link to Article
Ruo  LTickoo  SKlimstra  DS  et al.  Long-term prognostic significance of extent of rectal cancer response to preoperative radiation and chemotherapy. Ann Surg 2002;236 (1) 75- 81
PubMed Link to Article
Balch  GCMithani  SKShyr  Y  et al.  Prognostic significance of response to neoadjuvant chemoradiation therapy for rectal cancer [abstract 1047]. Proc Am Soc Clin Oncol 2003;22261
Garcíia-Aguilar  JHernandez de Anda  ESirivongs  PLee  SHMadoff  RDRothenberger  DA A pathologic complete response to preoperative chemoradiation is associated with lower local recurrence and improved survival in rectal cancer patients treated by mesorectal excision. Dis Colon Rectum 2003;46 (3) 298- 304
PubMed Link to Article
Janjan  NAAbbruzzese  JPazdur  R  et al.  Prognostic implications of response to preoperative infusional chemoradiation in locally advanced rectal cancer. Radiother Oncol 1999;51 (2) 153- 160
PubMed Link to Article
Shia  JGuillem  JGMoore  HG  et al.  Patterns of morphologic alteration in residual rectal carcinoma following preoperative chemoradiation and their association with long-term outcome. Am J Surg Pathol 2004;28 (2) 215- 223
PubMed Link to Article
National Cancer Institute, Surveillance, Epidemiology, and End Results (SEER) Program: SEER*Stat Database: Incidence, SEER 17 Regs Public-Use, Nov 2005 Sub (1973-2003 varying), Linked To County Attributes, Total US, 1969-2003 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April 2006, based on the November 2005 submission. http://www.seer.cancer.gov. Accessed June 1, 2007
National Cancer Institute, SEER: About the SEER Program.  Bethesda, MD National Cancer Institute2006;
Greene FL, Page DL, Fleming ID, et al, eds; American Joint Committee on Cancer, Cancer Staging Manual. 6th ed. New York, NY Springer2002;
Guillem  JGChessin  DBCohen  AM  et al.  Long-term oncologic outcome following preoperative combined modality therapy and total mesorectal excision of locally advanced rectal cancer. Ann Surg 2005;241 (5) 829- 838
PubMed Link to Article
Kim  CJYeatman  TJCoppola  D  et al.  Local excision of T2 and T3 rectal cancers after downstaging chemoradiation. Ann Surg 2001;234 (3) 352- 359
PubMed Link to Article
Schell  SRZlotecki  RAMendenhall  WMMarsh  RWVauthey  JNCopeland  EM  III Transanal excision of locally advanced rectal cancers downstaged using neoadjuvant chemoradiotherapy. J Am Coll Surg 2002;194 (5) 584- 591
PubMed Link to Article
Habr-Gama  APerez  RONadalin  W  et al.  Long-term results of preoperative chemoradiation for distal rectal cancer correlation between final stage and survival. J Gastrointest Surg 2005;9 (1) 90- 101
PubMed Link to Article
Habr-Gama  APerez  ROProscurshim  I  et al.  Patterns of failure and survival for nonoperative treatment of stage c0 distal rectal cancer following neoadjuvant chemoradiation therapy. J Gastrointest Surg 2006;10 (10) 1319- 1329
PubMed Link to Article
Moore  HGGittleman  AEMinsky  BD  et al.  Rate of pathologic complete response with increased interval between preoperative combined modality therapy and rectal cancer resection. Dis Colon Rectum 2004;47 (3) 279- 286
PubMed Link to Article
Martling  AHolm  TJohansson  HRutqvist  LECedermark  BStockholm Colorectal Cancer Study Group, The Stockholm II trial on preoperative radiotherapy in rectal carcinoma: long-term follow-up of a population-based study. Cancer 2001;92 (4) 896- 902
PubMed Link to Article
Hildebrandt  UKlein  TFeifel  GSchwarz  HPKoch  BSchmitt  RM Endosonography of pararectal lymph nodes: in vitro and in vivo evaluation. Dis Colon Rectum 1990;33 (10) 863- 868
PubMed Link to Article
Thaler  WWatzka  SMartin  F  et al.  Preoperative staging of rectal cancer by endoluminal ultrasound vs magnetic resonance imaging: preliminary results of a prospective, comparative study. Dis Colon Rectum 1994;37 (12) 1189- 1193
PubMed Link to Article
Tio  TLCoene  PPvan Delden  OMTytgat  GN Colorectal carcinoma: preoperative TNM classification with endosonography. Radiology 1991;179 (1) 165- 170
PubMed
Waizer  APowsner  ERusso  I  et al.  Prospective comparative study of magnetic resonance imaging vs transrectal ultrasound for preoperative staging and follow-up of rectal cancer: preliminary report. Dis Colon Rectum 1991;34 (12) 1068- 1072
PubMed Link to Article
Wudel  LJ  JrChapman  WCShyr  Y  et al.  Disparate outcomes in patients with colorectal cancer: effect of race on long-term survival. Arch Surg 2002;137 (5) 550- 556
PubMed Link to Article
Polite  BNDignam  JJOlopade  OI Colorectal cancer and race: understanding the differences in outcomes between African Americans and whites. Med Clin North Am 2005;89 (4) 771- 793
PubMed Link to Article
Polite  BNDignam  JJOlopade  OI Colorectal cancer model of health disparities: understanding mortality differences in minority populations. J Clin Oncol 2006;24 (14) 2179- 2187
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

Kaplan-Meier curves. A, Kaplan-Meier curve demonstrating improved disease-specific survival (P < .001) for patients with a good response to radiation therapy compared with those who fail to respond. The median survival was not reached in either group. B, Kaplan-Meier curve demonstrating improved overall survival for patients who respond to neoadjuvant radiation therapy compared with nonresponders (P < .001). The median survival was not reached for responders and was 7 years for nonresponders.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Kaplan-Meier curves. A, Kaplan-Meier curve demonstrating improved disease-specific survival (P = .01) for patients with stage I disease undergoing resection alone compared with patients who respond to neoadjuvant radiation therapy and have disease downstaged to stage 0 or I. The median survival was not reached for either group. B, Kaplan-Meier curve demonstrating similar overall survival in patients who are responders to neoadjuvant radiation therapy compared with patients with stage I rectal cancer undergoing resection alone. The curves were statistically significantly different (P = .04); however, the curves cross, giving the log-rank test low power to detect a true difference. The median survival was not reached for either group.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Demographic Characteristics of Patients With Rectal Cancer Grouped by Radiation Therapy
Table Graphic Jump LocationTable 2. Cox Regression of Disease-Specific and Overall Survivala
Table Graphic Jump LocationTable 3. Cox Regression of Disease-Specific and Overall Survival of Responders to Neoadjuvant Radiation Therapy vs Patients With Stage I Disease Undergoing Resection Alonea

References

National Cancer Institute, A Snapshot of Colorectal Cancer.  Bethesda, MD National Cancer Institute2006;
Fisher  BWolmark  NRockette  H  et al.  Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01. J Natl Cancer Inst 1988;80 (1) 21- 29
PubMed Link to Article
Gastrointestinal Tumor Study Group, Prolongation of the disease-free interval in surgically treated rectal carcinoma. N Engl J Med 1985;312 (23) 1465- 1472
PubMed Link to Article
Stockholm Colorectal Cancer Study Group, Randomized study on preoperative radiotherapy in rectal carcinoma. Ann Surg Oncol 1996;3 (5) 423- 430
PubMed Link to Article
Swedish Rectal Cancer Trial, Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med 1997;336 (14) 980- 987
PubMed Link to Article
Cedermark  BJohansson  HRutqvist  LEWilking  NStockholm Colorectal Cancer Study Group, The Stockholm I trial of preoperative short term radiotherapy in operable rectal carcinoma: a prospective randomized trial. Cancer 1995;75 (9) 2269- 2275
PubMed Link to Article
Kapiteijn  EMarijnen  CANagtegaal  ID  et al. Dutch Colorectal Cancer Group, Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 2001;345 (9) 638- 646
PubMed Link to Article
Sauer  RBecker  HHohenberger  W  et al. German Rectal Cancer Study Group, Preoperative vs postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004;351 (17) 1731- 1740
PubMed Link to Article
Cammà  CGiunta  MFiorica  FPagliaro  LCraxì  ACottone  M Preoperative radiotherapy for resectable rectal cancer: a meta-analysis. JAMA 2000;284 (8) 1008- 1015
PubMed Link to Article
Mohiuddin  MWinter  KMitchell  E  et al. Radiation Therapy Oncology Group Trial 0012, Randomized phase II study of neoadjuvant combined-modality chemoradiation for distal rectal cancer: Radiation Therapy Oncology Group Trial 0012. J Clin Oncol 2006;24 (4) 650- 655
PubMed Link to Article
Rullier  EGoffre  BBonnel  CZerbib  FCaudry  MSaric  J Preoperative radiochemotherapy and sphincter-saving resection for T3 carcinomas of the lower third of the rectum. Ann Surg 2001;234 (5) 633- 640
PubMed Link to Article
Ruo  LTickoo  SKlimstra  DS  et al.  Long-term prognostic significance of extent of rectal cancer response to preoperative radiation and chemotherapy. Ann Surg 2002;236 (1) 75- 81
PubMed Link to Article
Balch  GCMithani  SKShyr  Y  et al.  Prognostic significance of response to neoadjuvant chemoradiation therapy for rectal cancer [abstract 1047]. Proc Am Soc Clin Oncol 2003;22261
Garcíia-Aguilar  JHernandez de Anda  ESirivongs  PLee  SHMadoff  RDRothenberger  DA A pathologic complete response to preoperative chemoradiation is associated with lower local recurrence and improved survival in rectal cancer patients treated by mesorectal excision. Dis Colon Rectum 2003;46 (3) 298- 304
PubMed Link to Article
Janjan  NAAbbruzzese  JPazdur  R  et al.  Prognostic implications of response to preoperative infusional chemoradiation in locally advanced rectal cancer. Radiother Oncol 1999;51 (2) 153- 160
PubMed Link to Article
Shia  JGuillem  JGMoore  HG  et al.  Patterns of morphologic alteration in residual rectal carcinoma following preoperative chemoradiation and their association with long-term outcome. Am J Surg Pathol 2004;28 (2) 215- 223
PubMed Link to Article
National Cancer Institute, Surveillance, Epidemiology, and End Results (SEER) Program: SEER*Stat Database: Incidence, SEER 17 Regs Public-Use, Nov 2005 Sub (1973-2003 varying), Linked To County Attributes, Total US, 1969-2003 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April 2006, based on the November 2005 submission. http://www.seer.cancer.gov. Accessed June 1, 2007
National Cancer Institute, SEER: About the SEER Program.  Bethesda, MD National Cancer Institute2006;
Greene FL, Page DL, Fleming ID, et al, eds; American Joint Committee on Cancer, Cancer Staging Manual. 6th ed. New York, NY Springer2002;
Guillem  JGChessin  DBCohen  AM  et al.  Long-term oncologic outcome following preoperative combined modality therapy and total mesorectal excision of locally advanced rectal cancer. Ann Surg 2005;241 (5) 829- 838
PubMed Link to Article
Kim  CJYeatman  TJCoppola  D  et al.  Local excision of T2 and T3 rectal cancers after downstaging chemoradiation. Ann Surg 2001;234 (3) 352- 359
PubMed Link to Article
Schell  SRZlotecki  RAMendenhall  WMMarsh  RWVauthey  JNCopeland  EM  III Transanal excision of locally advanced rectal cancers downstaged using neoadjuvant chemoradiotherapy. J Am Coll Surg 2002;194 (5) 584- 591
PubMed Link to Article
Habr-Gama  APerez  RONadalin  W  et al.  Long-term results of preoperative chemoradiation for distal rectal cancer correlation between final stage and survival. J Gastrointest Surg 2005;9 (1) 90- 101
PubMed Link to Article
Habr-Gama  APerez  ROProscurshim  I  et al.  Patterns of failure and survival for nonoperative treatment of stage c0 distal rectal cancer following neoadjuvant chemoradiation therapy. J Gastrointest Surg 2006;10 (10) 1319- 1329
PubMed Link to Article
Moore  HGGittleman  AEMinsky  BD  et al.  Rate of pathologic complete response with increased interval between preoperative combined modality therapy and rectal cancer resection. Dis Colon Rectum 2004;47 (3) 279- 286
PubMed Link to Article
Martling  AHolm  TJohansson  HRutqvist  LECedermark  BStockholm Colorectal Cancer Study Group, The Stockholm II trial on preoperative radiotherapy in rectal carcinoma: long-term follow-up of a population-based study. Cancer 2001;92 (4) 896- 902
PubMed Link to Article
Hildebrandt  UKlein  TFeifel  GSchwarz  HPKoch  BSchmitt  RM Endosonography of pararectal lymph nodes: in vitro and in vivo evaluation. Dis Colon Rectum 1990;33 (10) 863- 868
PubMed Link to Article
Thaler  WWatzka  SMartin  F  et al.  Preoperative staging of rectal cancer by endoluminal ultrasound vs magnetic resonance imaging: preliminary results of a prospective, comparative study. Dis Colon Rectum 1994;37 (12) 1189- 1193
PubMed Link to Article
Tio  TLCoene  PPvan Delden  OMTytgat  GN Colorectal carcinoma: preoperative TNM classification with endosonography. Radiology 1991;179 (1) 165- 170
PubMed
Waizer  APowsner  ERusso  I  et al.  Prospective comparative study of magnetic resonance imaging vs transrectal ultrasound for preoperative staging and follow-up of rectal cancer: preliminary report. Dis Colon Rectum 1991;34 (12) 1068- 1072
PubMed Link to Article
Wudel  LJ  JrChapman  WCShyr  Y  et al.  Disparate outcomes in patients with colorectal cancer: effect of race on long-term survival. Arch Surg 2002;137 (5) 550- 556
PubMed Link to Article
Polite  BNDignam  JJOlopade  OI Colorectal cancer and race: understanding the differences in outcomes between African Americans and whites. Med Clin North Am 2005;89 (4) 771- 793
PubMed Link to Article
Polite  BNDignam  JJOlopade  OI Colorectal cancer model of health disparities: understanding mortality differences in minority populations. J Clin Oncol 2006;24 (14) 2179- 2187
PubMed Link to Article

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 12

Related Content

Customize your page view by dragging & repositioning the boxes below.

See Also...
Articles Related By Topic
Related Collections
PubMed Articles
JAMAevidence.com

The Rational Clinical Examination
Evidence Summary and Review 3