Clinical investigation
Rectum
The relationship of pathologic tumor regression grade (TRG) and outcomes after preoperative therapy in rectal cancer

These data were presented during the poster discussion session at the 44th Annual Meeting of ASTRO in New Orleans, LA, on October 6–10, 2002.
https://doi.org/10.1016/j.ijrobp.2004.11.017Get rights and content

Purpose: To examine the relationship between tumor regression grade (TRG) and outcomes in patients with rectal cancer treated with preoperative therapy.

Methods and Materials: Specimens from 144 patients with cT3,4 rectal cancer who had received preoperative radiation ± chemotherapy and had a minimum follow-up of 3 years were retrospectively reviewed. TRG, which involves examining the residual neoplastic cells and scoring the degree of both cytological changes, including nuclear pyknosis or necrosis and/or eosinophilia, as well as stromal changes, including fibrosis (either dense or edematous) with or without inflammatory infiltrate and giant-cell granulomatosis around ghost cells and keratin, was quantified in five grades according to the Mandard score (Cancer 1994;73:2680–2686). The greater the response, the lower the TRG score. The median follow-up was 72 months (range, 40–143 months).

Results: Of the 144 patients, 19% were TRG1, 12% were TRG2, 21% were TRG3, 46% were TRG4, and 1% were TRG5. To simplify the analysis, TRG was combined into two groups: TRG1–2 and TRG3–5. By univariate analysis, none of the pretreatment factors examined, including age, circumference, length, distance from the anorectal ring, pretreatment T and N stage, and INDpre (defined as the pretreatment reference index size based on digital rectal examination), had an impact on 5-year outcomes, including local control, metastases-free survival, disease-free survival, and overall survival. Postoperative parameters, including pathologic T stage (pT), pathologic N stage (pN), and TRG, did significantly influence 5-year outcomes. These included local failure: pT0–2: 5% vs. pT3–4: 19%, p = 0.007; pN0: 7% vs. pN1–3: 26%, p = 0.002; TRG1–2: 2% vs. TRG3–5: 17%, p = 0.013; metastasis-free survival: pT0–2: 86% vs. pT3–4: 62%, p = 0.005; pN−: 86% vs. pN*: 42%, p < 0.001; TRG1–2: 91% vs. TRG3–5: 66%, p = 0.004; disease-free survival: pT0–2: 83% vs. pT3–4: 54%, p = 0.001; pN0: 80% vs. pN1–3: 39%, p < 0.001; TRG1–2: 91% vs. TRG3–5: 58%, p < 0.001; and overall survival: pT0–2: 85% vs. pT3–4: 65%, p = 0.007; pN0: 86% vs. pN1–3: 45%, p < 0.001; TRG1–2: 89% vs. TRG3–5: 68%, p = 0.004. By multivariate analysis combining all pre- and posttreatment parameters, only pN (p < 0.001) and TRG (p = 0.005) significantly predicted disease-free survival. Furthermore, TRG predicted the incidence of pathologic nodal involvement (p < 0.0001).

Conclusions: By univariate analysis, TRG is a predictor for local failure, metastases-free survival, and overall survival. By multivariate analysis, it predicts improved disease-free survival. Given the ability of TRG to predict those patients with N* disease, it may be helpful, in combination with other clinicopathologic factors, in selecting patients for a more conservative procedure, such as local excision rather than radical surgery, after preoperative therapy.

Introduction

In the last several years, a number of studies examining the use of preoperative chemoradiation (CMT) in patients with cT3–4 rectal cancer have reported pathologic complete response rates (pCR) of 9–29%, as well as an increased ability to perform sphincter-sparing surgery (1, 2, 3, 4, 5, 6).

Many series report that patients who achieve a pCR after preoperative CMT, independent of their initial clinical T and N stage, have improved long-term outcomes, including local control, metastases-free survival, and overall survival (6, 7, 8, 9, 10, 11, 12). In patients who achieve less than a pCR, there is heterogeneity in definitions and techniques of identifying and scoring the presence of residual tumor after preoperative CMT. For example, stage pT3 has been defined as responses ranging from gross disease remains in the perirectal fat to those with a few foci of microscopic residual disease outside the bowel wall. Most series report that the degree of response is predictive of outcomes (6, 10). For example, Wheeler et al. have suggested that patients with only microscopic foci in the mesorectum had a better prognosis compared with patients with T3 (transmural) disease (13).

The aim of this study is to evaluate the relationship between the tumor regression grade (TRG) pathologic scoring system, which is based on the characteristics of the disposition of residual neoplastic cells in the specimen, and 5-year outcomes in patients with rectal cancer treated with preoperative radiation therapy with or without concomitant chemotherapy.

Section snippets

Methods and materials

A total of 216 patients with cT3–4 and/or N* rectal cancer were treated with preoperative radiation with or without concurrent chemotherapy between March 1990 and February 2000 in the Department of Radiation Oncology at the Catholic University, Rome, Italy. For this analysis, 144 patients were identified who had a minimum follow-up of 3 years and the availability of the pathologic specimen for the determination of TRG score. The remaining 72 patients were excluded because of inadequate

Patient characteristics (pretreatment)

A total of 144 patients (96 male, 48 female) with a minimum follow-up of 3 years had TRG analysis of pathologic specimen. The median age was 64 years (range, 25–81 years). The tumor stage at initial (pretreatment) diagnosis and tumor grade are seen in Table 1.

The median length of the tumor was 50 mm (SD, 17.6, range, 10–150 mm). The number of quarters of rectal wall invaded by the tumor were measured on CT scan images; the results are as follows: 1 wall, 8 (6%); 2 walls, 69 (48%); 3 walls, 17

Discussion

Retrospective data suggest that pathologic downstaging after preoperative radiotherapy with or without concomitant chemotherapy is associated with improved outcomes (6, 7, 8, 9, 10, 12). Patients with pT0–2 stage disease after preoperative therapy have local failure rates of 0–6% and 5-year survivals of 90–100%. However, there is heterogeneity in the definitions as well as the techniques of identifying and scoring the presence of residual tumor after preoperative therapy. Therefore, we have

Conclusion

Tumor regression grade seems to be a prognostic factor for disease-free survival in patients receiving preoperative therapy for rectal cancer. In addition, it is a prognostic factor for local failure, metastasis-free survival, and overall survival. Given the ability of TRG to predict those patients with N* disease, in combination with other clinicopathologic factors, it may be helpful after preoperative therapy in selecting patients for a more conservative procedure, such as local excision

References (31)

  • C. Rodel et al.

    Apoptosis as cellular predictor for histopathologic response to neoadjuvant radiochemotherapy in patients with rectal cancer

    Int J Radiat Oncol Biol Phys

    (2002)
  • R.S. Chari et al.

    Preoperative radiation and chemotherapy in the treatment of adenocarcinoma of the rectum

    Ann Surg

    (1995)
  • A. Grann et al.

    Preliminary results of preoperative 5-fluorouracil, low-dose Leucovorin and concurrent radiation therapy for clinically resectable T3 rectal cancer

    Dis Colon Rectum

    (1997)
  • J.P. Gerard et al.

    Preoperative radiotherapy of rectal cancerThe Lyons experience, 1985–1996. Prognostic study apropos of 312 patients

    Ann Chir

    (1999)
  • L. Ruo et al.

    Long-term prognostic significance of extent of rectal cancer response to preoperative radiation and chemotherapy

    Ann Surg

    (2002)
  • Cited by (364)

    View all citing articles on Scopus
    View full text