Tumor Regression Grading as Prognostic Factor in Patients with Locally Advanced Rectal Cancer Treated with Preoperative Radiochemotherapy

Reviewer: S. Jack Wei, MD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 12 de octubre del 2004

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Presenter: C. Roedel
Presenter's Affiliation: German Rectal Cancer Trial Group
Type of Session: Scientific

Background

  • It has been previously reported by the German Rectal Cancer Trial Group that preoperative chemoradiatherapy (CTRT) for rectal cancer improves local control, improves the rate of sphincter function preservation, and may decrease toxicity compared to postoperative therapy.
  • The Tumor Regression Grading (TRG) is a measure of the amount of response of a tumor to chemotherapy and radiation therapy.
  • Several previous studies have shown that increasing the time between preoperative CTRT and surgical resection for rectal cancer has lead to improved TRG and subsequently improved rates of sphincter sparing resections.
  • However, it is unclear if TRG varies among patients for the same type of tumor that are treated in similar fashions.
  • In addition, it is unknown if the TRG impacts on outcome if a patient is able to undergo a pathologic complete resection despite the amount of TRG.
  • The current study retrospectively examines the TRG for patients undergoing preoperative CTRT to address these issues.

Materials and Methods

  • All patients in the study had rectal adenocarcinoma that was either T3 or T4 or had node positive disease.
  • 320 patients were treated preoperatively with concurrent CTRT consisting of 5-FU (1g/m2/d wks1&5).  Only patients treated preoperatively were included in this analysis.
  • Radiation was given in 1.8 Gy daily fractions to a total dose of 50.4 Gy.
  • Patients were taken for surgical resection 6 weeks after completion of CTRT with the vast majority undergoing surgery between 5 and 7 weeks after CTRT.
  • Pathologic TRG was assessed as follows:
    TRG 0       No response or progressive disease
    TRG 1       <25% reduction in tumor volume
    TRG 2       25-50% reduction in tumor volume
    TRG 3       >50% reduction in tumor volume
    TRG 4       Complete response

Results

  • Percent of patients with TRG Grade:
    TRG 0       8.3%
    TRG 1       15.3%
    TRG 2       13.8%
    TRG 3       52.2%
    TRG 4       10.3%
  • 10% of patients with TRG 4 (complete response) were found to have nodal involvement at time of surgery.
  • 5-year Disease-Free Survival (DFS) by TRG:
    TRG 0-1    63%
    TRG 2-3    75%
    TRG 4       80%
    p=0.017
  • 5-year Local Recurrence by TRG:
    TRG 0-1    6%
    TRG 2-3    4%
    TRG 4       0%
    p=NS
  • 5-year Distant Metastatic Rate by TRG:
    TRG 0-1    34%
    TRG 2-3    25%
    TRG 4       14%
    p<0.05
  • Residual T3 or T4 tumor after preoperative CTRT was prognostic for DFS (p=0.002)
  • On multivariate analysis, the most predictive factor for DFS was node positivity after preoperative CTRT.  5-year DFS was 85% for node negative patients vs. 46% for node positive patients

Author's Conclusions

  • TRG varies for the same types of tumors despite uniform treatment
  • TRG after preoperative CTRT is prognostic for DFS and may help guide further treatement

Clinical/Scientific Implications

The current study shows that despite uniform treatment, patients with similar types of tumors have varying degrees of response to treatment.  This illustrates a very important aspect of cancer biology: inherent differences exist among tumors which affects a tumor's growth rate, response to treatment, and the ultimate outcome in an individual patient.  This study shows that these inherent differences, which can be seen by differences in response to treatment, can lead to differing outcome among patients with similar tumors.  The concept of tumor heterogeneity is an emerging field in oncologic research.  Increasingly, physicians and scientists are attempting to identify patients with relative susceptibility or resistance to treatment or with tumors that behave more or less aggressively, so that treatment can be altered to adjust for these differences.  As research progresses, it is likely that the days of a "one-size-fits-all" approach to cancer management are numbered.   Instead, the future of oncologic treatment will likely include "tailored" treatment, customized to the inherent aspects of a given patient's cancer.


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