Clinical Investigation
Clinical Parameters Predicting Pathologic Tumor Response After Preoperative Chemoradiotherapy for Rectal Cancer

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Purpose

To identify pretreatment clinical parameters that could predict pathologic tumor response to preoperative chemoradiotherapy (CRT) for rectal cancer.

Methods and Materials

The study involved 351 patients who underwent preoperative CRT followed by surgery between October 2001 and July 2006. Tumor responses to preoperative CRT were assessed in terms of tumor downstaging and tumor regression. Statistical analyses were performed to identify clinical factors associated with pathologic tumor response.

Results

Tumor downstaging (defined as ypT2 or less) was observed in 167 patients (47.6%), whereas tumor regression (defined as Dworak's Regression Grades 3 or 4) was observed in 103 patients (29.3%) and complete regression in 51 patients (14.5%). Multivariate analysis found that predictors of downstaging were pretreatment hemoglobin level (p = 0.045), cN0 classification (p < 0.001), and serum carcinoembryonic antigen (CEA) level (p < 0.001), that predictors of tumor regression were cN0 classification (p = 0.044) and CEA level (p < 0.001), and that the predictor of complete regression was CEA level (p = 0.004).

Conclusions

The data suggest that pretreatment CEA level is the most important clinical predictor of pathologic tumor response. It may be of benefit in the selection of treatment options as well as the assessment of individual prognosis.

Introduction

Postoperative chemoradiotherapy (CRT) improves local control and survival in locally advanced rectal cancer (1). In the past, radical surgery followed by postoperative CRT was considered standard treatment. However, preoperative CRT for advanced rectal cancer has been increasingly used in recent years and has now become a standard treatment, and a recent prospective, randomized trial confirmed the superiority of preoperative over postoperative CRT in terms of local control and toxicity (2).

In contrast to the postoperative setting, preoperative CRT allows a relatively short-term evaluation because it offers alternative endpoints based on pathologic tumor response. The most commonly used endpoint is tumor downstaging. Numerous studies have reported that tumor downstaging after preoperative radiotherapy with or without chemotherapy followed by surgical resection is associated with decreased recurrence and improved survival 3, 4, 5, 6, 7, 8, 9. Another endpoint for assessing pathologic tumor response is tumor regression grade after preoperative CRT. A variety of definitions and techniques for identifying and scoring the residual cancer exist, and several studies have reported correlations between tumor regression grade and long-term clinical outcomes 8, 10, 11, 12. On the basis of these reports, the ability to predict the pathologic tumor response before treatment would be of clinical advantage in that it may provide additional information for permitting tailored treatment options as well as for assessing the individual prognosis.

Using specific molecular markers or gene expression profiling, many translational studies have sought to identify the biologic properties of tumors that might predict therapeutic response 13, 14, 15, 16, 17, 18, 19. Although those studies identified a number of potentially important predictors, the results have not yet had clinical impact owing to variable findings between studies and because the techniques used are complex and time consuming in terms of clinical application. Thus, despite numerous studies, neither molecular marker nor gene expression profiling data have identified definitive predictors of tumor response. In contrast, there has been no systematic investigation of clinical parameters that may predict preoperative CRT tumor response.

With this background, the present study sought to identify pretreatment clinical parameters that may predict pathologic tumor response to preoperative CRT.

Section snippets

Patients

Between October 2001 and July 2006, 388 patients with primary rectal cancer underwent preoperative CRT at the National Cancer Center, Republic of Korea. Medical records were reviewed to analyze clinical prognostic parameters and to identify the following inclusion criteria: (1) histologically confirmed rectal adenocarcinoma, (2) tumor located within 8 cm of the anal verge, (3) locally advanced (cT3-4 classification) and curatively resectable tumor evaluated with magnetic resonance imaging (MRI)

Patient characteristics

Of the 388 patients, 20 refused surgery, 7 were treated with transanal excision because of comorbidities or strong refusal of anal ablation, and 10 were transferred to other hospitals closer to their residence. Therefore, 351 patients who met the inclusion criteria were analyzed in this study. Table 1 shows detailed patient characteristics. The study population was mostly male (66.7%) and had a median age of 57 years (range, 31–83 years). Almost all patients had a cT3 classification of their

Discussion

A wide spectrum of tumor responses has been reported after preoperative CRT for locally advanced rectal cancer, and the clinical meaning of such responses in terms of prognosis has been the subject of many investigations. Tumor response prediction before surgery may be of benefit to effective management. The prognostic factors for predicting long-term clinical outcomes have mostly been based on histopathologic parameters after curative resection in preoperative setting studies 3, 4, 5, 6, 7, 8,

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  • Cited by (0)

    Supported by the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (Grant No. 0412-CR01-0704-0001).

    Conflict of interest: none.

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