Tumor Regression Grading Prognostic in Rectal Cancer

Megan Brooks

April 24, 2014

New research confirms the prognostic value of tumor regression grading (TRG) after preoperative chemoradiotherapy (CRT) for locally advanced rectal carcinoma.

At 10 years, complete and intermediate tumor regression after preoperative CRT was associated with improved metastasis-free and disease-free survival, independent of clinicopathologic parameters, according to updated results from the CAO/ARO/AIO-94 trial.

"Biologically, this is an exciting finding, as poor tumor regression reflects an inherently aggressive malignant biologic disease that is, at the same time, less responsive to CRT and more likely to develop distant metastases," said study investigator Emmanouil Fokas, MD, from the Department of Radiotherapy and Oncology at the University of Frankfurt in Germany.

"The clinical implication is important, as it can help identify different prognostic groups when treated homogeneously," Dr. Fokas told Medscape Medical News. "Indeed, there is an ongoing discussion on whether TRG could help in adapting treatment toward a more or less aggressive route, depending on the response to CRT in patients with rectal cancer," he explained.

Although there is "still work to be done, it is expected that TRG will improve clinical decision making in the near future," he noted.

The 10-year follow-up data confirm earlier findings from the CAO/ARO/AIO-94 trial, which demonstrated the superiority of preoperative over postoperative CRT for local control.

The new results were published online April 21 in the Journal of Clinical Oncology.

In 2005, the investigators reported that, in an exploratory analysis of TRG data, complete pathologic response (TRG 4) and intermediate pathologic response (TRG 2+3) after preoperative CRT were associated with improved disease-free survival after a median follow-up of 41 months (J Clin Oncol. 2005;23:8688-8696).

Now, they report long-term TRG data from the trial after a median follow-up of 132 months. TRG after preoperative CRT was determined in 386 surgical specimens, ranging from TRG 4 (no viable tumor cells) to TRG 0 (no signs of regression).

At 10-years, the rate of distant metastasis was significantly lower (P = .005) and disease-free survival significantly higher (P = .008) for TRG 4 (complete regression) than for TRG 2+3 (intermediate regression) and TRG 0+1 (poor regression), they report.

Table: Ten-Year Outcomes by TRG Status

Outcome TRG 4, % TRG 2+3, % TRG 0+1, %
Distant metastasis 10.5 29.3 39.6
Disease-free survival 89.5 73.6 63.0


"Robust" Analysis

The investigators note that the 3-tiered TRG classification system needs to be prospectively tested in multiple datasets to validate its reproducibility in a wider setting.

"Future trials should be specifically designed to validate the impact of TRG on patient-relevant goals. Also, a consensus for a universally approved tumor regression classification is needed," Dr. Fokas said.

This is a "well-designed and robust analysis" of the prognostic impact of TRG in patients with rectal adenocarcinoma treated by preoperative CRT and total mesorectal excision, according to an accompanying editorial.

"Previously published studies from other groups have reported similar results, including a significant impact of TRG on local control, incidence of metastasis, disease-free survival, and overall survival," write Vincenzo Valentini, MD, from the Policlinico Universitario A. Gemelli in Rome, Italy, and Bruce D. Minsky, MD, from the University of Texas M.D. Anderson Cancer Center in Houston.

"This study, however, differs from others reported in the literature because of the homogeneity of the surgical and adjuvant treatments performed, large number of prospectively enrolled patients, and long follow-up (median, 132 months)," they point out.

The editorialists agree that more study is needed. There are a number of suggested methods for assessing tumor regression after preoperative therapy, and the various classification systems proposed for rectal cancer "need to be cross-validated for their predictive value and reproducibility in a broader setting."

"While we await these additional studies, TRG provides a valuable tool to assist in clinical decision making," Drs. Valentini and Minsky conclude.

The study was supported by a grant from German Cancer Aid. Dr. Fokas, Dr. Valentini, and Dr. Minsky have disclosed no relevant financial relationships. Two of the study authors report relationships with Roche and sanofi-aventis.

J Clin Oncol. Published online April 21, 2014. Abstract, Editorial


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