September 2, 2011 — Magnetic resonance imaging (MRI) assessment of rectal tumors before surgery predicts both disease-free and overall survival, which ultimately might help clinicians provide better treatment planning, according to the authors of a study published online August 29 in the Journal of Clinical Oncology.
In this study of 111 patients with locally advanced rectal cancer, participants were evaluated with MRI after neoadjuvant chemotherapy or radiation. The imaging tool assessed tumor regression grade (TRG), which indicates how much of the tumor has been replaced with fibrotic tissue and, thus, how well it responded to the therapy that preceded surgery. Patients were categorized as either "good" or "poor" responders, based on their MRI-based TRG.
The 5-year survival for patients with a poor response was 27%; for those with a good response, it was 72% (P = .001). The 5-year disease-free survival for poor responders was 31%; for good responders, it was 64% (P = .007).
The study's preoperative findings might help clinicians and their patients, suggest the investigators. The MRI evaluation "gives the multidisciplinary team a window of opportunity to refine treatment plans before definitive surgery," write the authors, led by Uday Patel, MD, from the Royal Marsden Hospital in Sutton, United Kingdom.
The authors cite 2 examples of potential changes in treatment plans.
"The role of systemic non-cross-resistant chemotherapy could be tested in patients with poor response, and the evaluation of the timing or even deferral of surgical resection could be tested in patients with good response," they write.
The study is a novel contribution to the literature. "This is the first time that a prospective study has demonstrated a correlation between radiologically determined tumor response and long-term outcomes," the authors say. Previously, MRI has been used to assess tumor response before surgical resection and to "enable appropriate selection of patients" for adjuvant therapy in this setting — but not outcomes.
Impact on Management
The findings have the potential to significantly affect the management of patients with rectal cancer, suggested an expert not involved with the study.
Performing MRI after initial chemoradiation therapy and before surgery might identify patients who could benefit from more aggressive therapy prior to surgery, agreed Morton Kahlenberg, MD, from the University of Texas Health Science Center, San Antonio, who is a member of the American Society of Clinical Oncology Cancer Communications Committee.
"This could change the standard of care for these patients, since using MRI may suggest the need for further treatment before surgery. Clinical trials are needed to address this important question," Dr. Kahlenberg commented in a press statement.
"Now Possible" to Assess Tumor Regression Before Surgery
In rectal cancer to date, the postsurgical pathologic assessment of TRG — and the degree of cancer tissue that is converted into fibrotic tissue — has been considered "an important predictor" of disease-free survival and a predictor of overall survival, say the authors.
A previously developed MRI-based TRG system, known as MERCURY (Magnetic Resonance Imaging in Rectal Cancer European Equivalence Study), was used in this study. Researchers from 5 countries enrolled patients who were considered to be high risk and who required preoperative therapy for downstaging or downsizing of the primary tumor. To qualify, patients had to have had tumors that were, on baseline pretreatment scans, categorized as advanced T3c, T3d, or T4, and had to have the potential involvement of circumferential resection margin or cancer at the tumor edges after surgery.
The 111 study participants underwent either preoperative chemoradiotherapy or long-course radiotherapy before total mesorectal excision surgery, and then underwent MRI after these treatments.
The MRI scans were reviewed to determine the degree of tumor replacement with fibrotic tissue and, thus, their TRG. On multivariate analysis, the MRI-assessed TRG hazard ratios (HRs) were independently significant for survival (HR, 4.40; 95% confidence interval [CI], 1.65 to 11.7) and disease-free survival (HR, 3.28; 95% CI, 1.22 to 8.80), the investigators report.
The study's MRI-determined TRG findings are an important achievement because TRG has heretofore been determined only after surgery by standard pathology, note the authors. "The relationship between pathologic TRG and outcome has been considered important in previous studies...in predicting [overall survival] and [disease-free survival]," write the authors. "Applying similar principles with MRI, we have now shown that it is possible to assess tumor regression before surgery."
In addition to assessing TRG, the investigators evaluated circumferential resection margin status after chemoradiotherapy. This is an important measure because it refers to either the remaining cancer at the tumor edges after treatment or to that predicted to remain after surgery. A positive surgical margin is considered a strong predictor of local recurrence, say the authors.
Indeed, the investigators found that preoperative MRI-evaluated circumferential resection margin independently predicted local recurrence (HR, 4.25; 95% CI, 1.45 to 12.51).
The study also included assessment of pathology staging by tumor and node.
Earlier studies have shown that histopathologic assessment of tumor and node tissue cells after surgery can predict local recurrence, disease-free survival, and overall survival, explain the authors. Of course, this assessment takes place after surgery and its value is limited by that fact, but it serves as a measuring stick for MRI.
In this study, T substaging for pathology (ypT stage, assessed after surgery) was standardized, say the authors. "Good" ypT stage was defined as stages T0, T1, T2, and T3a; "poor" was defined as stages T3b, T3c, T3d, and T4.
Five-year survival for poor posttreatment pathologic T stage (ypT) was 39%, compared with 76% for those assessed with good T stage (P = .001). Disease-free survival for the same was 38% vs 84% (P = .001), and local recurrence was 27% vs 6% (P = .018).
"Our data also show that both MRI T staging and TRG showed statistical correlation with ypT," write the authors about the relation between MRI-derived findings and the more traditional postsurgery pathologic findings.
Finally, the 5-year survival for patients with involved circumferential resection margin on pathology was 30%, compared with 59% for those without the involvement (P = .001), disease-free survival was 28% vs 62% (P = .02), and local recurrence was 56% vs 10% (P = .001).
Pathology node status did not predict outcomes, the authors note.
The study was supported by educational grants from Siemens Medical UK and the Pelican Cancer Foundation, by a program grant from Yorkshire Cancer Research, and by the National Institute for Health Research Biomedical Research Center. The authors have disclosed no relevant financial relationships.
J Clin Oncol. Published online August 29, 2011. Abstract
In this study of 111 patients with locally advanced rectal cancer, participants were evaluated with MRI after neoadjuvant chemotherapy or radiation. The imaging tool assessed tumor regression grade (TRG), which indicates how much of the tumor has been replaced with fibrotic tissue and, thus, how well it responded to the therapy that preceded surgery. Patients were categorized as either "good" or "poor" responders, based on their MRI-based TRG.
The 5-year survival for patients with a poor response was 27%; for those with a good response, it was 72% (P = .001). The 5-year disease-free survival for poor responders was 31%; for good responders, it was 64% (P = .007).
The study's preoperative findings might help clinicians and their patients, suggest the investigators. The MRI evaluation "gives the multidisciplinary team a window of opportunity to refine treatment plans before definitive surgery," write the authors, led by Uday Patel, MD, from the Royal Marsden Hospital in Sutton, United Kingdom.
The authors cite 2 examples of potential changes in treatment plans.
"The role of systemic non-cross-resistant chemotherapy could be tested in patients with poor response, and the evaluation of the timing or even deferral of surgical resection could be tested in patients with good response," they write.
The study is a novel contribution to the literature. "This is the first time that a prospective study has demonstrated a correlation between radiologically determined tumor response and long-term outcomes," the authors say. Previously, MRI has been used to assess tumor response before surgical resection and to "enable appropriate selection of patients" for adjuvant therapy in this setting — but not outcomes.
Impact on Management
The findings have the potential to significantly affect the management of patients with rectal cancer, suggested an expert not involved with the study.
Performing MRI after initial chemoradiation therapy and before surgery might identify patients who could benefit from more aggressive therapy prior to surgery, agreed Morton Kahlenberg, MD, from the University of Texas Health Science Center, San Antonio, who is a member of the American Society of Clinical Oncology Cancer Communications Committee.
"This could change the standard of care for these patients, since using MRI may suggest the need for further treatment before surgery. Clinical trials are needed to address this important question," Dr. Kahlenberg commented in a press statement.
"Now Possible" to Assess Tumor Regression Before Surgery
In rectal cancer to date, the postsurgical pathologic assessment of TRG — and the degree of cancer tissue that is converted into fibrotic tissue — has been considered "an important predictor" of disease-free survival and a predictor of overall survival, say the authors.
A previously developed MRI-based TRG system, known as MERCURY (Magnetic Resonance Imaging in Rectal Cancer European Equivalence Study), was used in this study. Researchers from 5 countries enrolled patients who were considered to be high risk and who required preoperative therapy for downstaging or downsizing of the primary tumor. To qualify, patients had to have had tumors that were, on baseline pretreatment scans, categorized as advanced T3c, T3d, or T4, and had to have the potential involvement of circumferential resection margin or cancer at the tumor edges after surgery.
The 111 study participants underwent either preoperative chemoradiotherapy or long-course radiotherapy before total mesorectal excision surgery, and then underwent MRI after these treatments.
The MRI scans were reviewed to determine the degree of tumor replacement with fibrotic tissue and, thus, their TRG. On multivariate analysis, the MRI-assessed TRG hazard ratios (HRs) were independently significant for survival (HR, 4.40; 95% confidence interval [CI], 1.65 to 11.7) and disease-free survival (HR, 3.28; 95% CI, 1.22 to 8.80), the investigators report.
The study's MRI-determined TRG findings are an important achievement because TRG has heretofore been determined only after surgery by standard pathology, note the authors. "The relationship between pathologic TRG and outcome has been considered important in previous studies...in predicting [overall survival] and [disease-free survival]," write the authors. "Applying similar principles with MRI, we have now shown that it is possible to assess tumor regression before surgery."
In addition to assessing TRG, the investigators evaluated circumferential resection margin status after chemoradiotherapy. This is an important measure because it refers to either the remaining cancer at the tumor edges after treatment or to that predicted to remain after surgery. A positive surgical margin is considered a strong predictor of local recurrence, say the authors.
Indeed, the investigators found that preoperative MRI-evaluated circumferential resection margin independently predicted local recurrence (HR, 4.25; 95% CI, 1.45 to 12.51).
The study also included assessment of pathology staging by tumor and node.
Earlier studies have shown that histopathologic assessment of tumor and node tissue cells after surgery can predict local recurrence, disease-free survival, and overall survival, explain the authors. Of course, this assessment takes place after surgery and its value is limited by that fact, but it serves as a measuring stick for MRI.
In this study, T substaging for pathology (ypT stage, assessed after surgery) was standardized, say the authors. "Good" ypT stage was defined as stages T0, T1, T2, and T3a; "poor" was defined as stages T3b, T3c, T3d, and T4.
Five-year survival for poor posttreatment pathologic T stage (ypT) was 39%, compared with 76% for those assessed with good T stage (P = .001). Disease-free survival for the same was 38% vs 84% (P = .001), and local recurrence was 27% vs 6% (P = .018).
"Our data also show that both MRI T staging and TRG showed statistical correlation with ypT," write the authors about the relation between MRI-derived findings and the more traditional postsurgery pathologic findings.
Finally, the 5-year survival for patients with involved circumferential resection margin on pathology was 30%, compared with 59% for those without the involvement (P = .001), disease-free survival was 28% vs 62% (P = .02), and local recurrence was 56% vs 10% (P = .001).
Pathology node status did not predict outcomes, the authors note.
The study was supported by educational grants from Siemens Medical UK and the Pelican Cancer Foundation, by a program grant from Yorkshire Cancer Research, and by the National Institute for Health Research Biomedical Research Center. The authors have disclosed no relevant financial relationships.
J Clin Oncol. Published online August 29, 2011. Abstract
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