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MRI is superior to CT for liver staging in colon cancer and should be investigated as the definitive liver staging modality in colon cancer

Alexandra W. Acher¹, Emily Winslow², and Scott B. Reeder¹
¹University of Wisconsin School of Medicine and Public Health, Madison, WI, United States, ²Georgetown University, Washington DC, MD, United States

Synopsis

Colon cancer is the 3rd most common cancer in the United States. Unfortunately, most patients present with Stage III or IV disease and disease recurrence is high despite advanced in systemic therapies. Despite evidence that gadoxetic acid-enhanced MRI is superior for the detection and diagnosis of colon cancer liver metastases, computed tomography remains the recommended staging and surveillance modality. The purpose of this abstract is to synthesize and analyze the evidence regarding the accuracy of liver MRI to stage and surveil CCLM, and to identify knowledge gaps to inform future research on staging and surveillance imaging for CCLM.

Introduction

Colon cancer (CC) is the 3rd most common cancer in the United States¹. Unfortunately, 35% of patients present with stage III1 and 25% present with stage IV disease2, 37.5% of whom are resectabe^2-4. Even with curative intent treatment, 5 year recurrence is high: 3-37% for Stage I-II, 20-57% for stage III, and 60-80% for stage IV disease^3,5,6, with 2% of Stage II, 2-15% of Stage III, and 45-50% of Stage IV recurring within 12 months of surgery (early recurrence)^7-9. These rates of recurrence are summarized in Figure 1. Given the survival benefit associated with oncologic hepatic metastectomy,^8-15 accurate staging and surveillance imaging diagnostics are imperative for optimized treatment. The National Comprehensive Cancer Network recommends multidetector computed tomography (MDCT) for staging and surveillance of all CC16, despite evidence that MRI is more sensitive and specific for defining CC liver metastases (CCLM)^17-26. The purpose of this abstract is to synthesize and analyze the evidence regarding the accuracy of liver MRI to stage and surveil CCLM, and to identify knowledge gaps to inform future research on staging and surveillance imaging for CCLM.

Diagnostic Performance of MDCT and MRI

When MDCT imaging is optimized for detecting CCLM, the sensitivity and specificity varies between 60-85%^19,27,28 and 80-95%²⁸, respectively. However, the mean sensitivity of MDCT is 65% for lesions < 1cm^21-26,29 and only 8% for lesions < 0.5cm²³, and further diminished by background hepatic steatosis^32,35,39,40. Dissemination of MRI systems with high-performance gradients, high magnetic field strength, high channel count phased arrays coils, advanced 3D breath-hold and free-breathing dynamic T1 weighted sequences, and diffusion weighted imaging (DWI) has improved detection of even subtle CCLM. Hepatobiliary gadolinium-based contrast agents, i.e. gadoxetic acid (GA), further improve the ability of MRI to detect and characterize focal liver lesions^30,31. In addition to GA-enhanced MRI, sequences recommended to detect and characterize liver lesions include fat suppressed T2-weighted fast spin-echo, 3D fat-suppressed SGRE T1-weighted, fat sensitive in- and out-of-phase (IOP) T1w SGRE, pre- and post-contrast dynamic T1w imaging during late arterial, portal venous, and delayed phases, and DWI^29,32-34. The cumulative sensitivity and specificity of these sequences for diagnosing CCLM is 85-98% and 80-90%, respectively^{18-23,26,35-38}, with a sensitivity > 90% for lesions < 1cm²⁰. The use of GA in combination with these sequences is increasingly regarded as the standard of care for detection and characterization of CCLM²⁰.

Early Recurrence – Actual Recurrence or Occult Disease?

Early hepatic recurrence is hypothesized to represent patients with more aggressive disease biology^8,39 or disease occult to imaging at staging^7,9,40. In support of the latter, trials comparing diagnostic accuracy of preoperative MDCT and GA-enhanced MRI for focal liver lesions found that 17% of patients had a change in their surgical plan after MRI³⁸. Retrospective comparison of the sensitivity of MDCT and MRI for detecting liver metastases found that MRI detected additional lesions in 40% of patients, a 6-fold increase in detection of lesions < 1 cm, and resulted in a change in treatment plan in 37% of patients¹⁹.

Potential Clinical Impact of Staging MRI on Clinical Outcomes

The potential impact of staging MRI is summarized in Figure 2. Assuming some proportion of “early recurrence” represents occult CCLM at CT-staging, the additive benefit of liver MRI can be estimated. Of the 101,420 CC diagnoses in 2019, 40% were Stage I-II, 35% were Stage III and 25% were Stage IV⁴¹. Assuming 2-15% of stage III disease will recur within 12 months⁴², 710 to 5,324 patients may have had occult hepatic metastases at staging. Assuming 95% sensitivity for MRI, occult disease may have been detected in 675 to 5,058 patients, which equates to 1 in 52 (assuming 2% early recurrence rate) or 1 in 7 (assuming 15% early recurrence rate) patients. Similarly, if early hepatic recurrence for stage IV patients who underwent curative intent surgery is 50%7-9, hepatic staging with MRI may change treatment in 4,516, or 1 in 5, of these patients.

Gaps in Knowledge

The above calculations are based on limited existing clinical data on the incidence and rates of recurrence of CC. Most studies are retrospective, use data from 1980 through early 2000, do not account for systemic therapy advancements, the advent of personalized oncology targeting tumor-specific mutations⁵⁷, liver hypertrophy modalities, ablation techniques, and the utilization of hepatic metastectomy. Additionally, data on the incidence of resectable stage IV disease are limited. Although synchronous liver metastases are reported to occur in 15% of all CC and are isolated to the liver in 75% of stage IV patients⁵, quantification of resectable hepatic disease is lacking. Studies describe that 10-37% of patients present with resectable disease^5,6, however, there are no standardized criteria for determining resectability. Not accounting for these factors makes data interpretation difficult. Prospective studies that delineate the resectability of stage IV disease and the incidence and timing of hepatic recurrence are needed.

Conclusion and Future Directions

Our analysis demonstrates that staging MRI may change management in 1 in 7 of Stage III patients and 1 in 5 Stage IV patients. Given the incidence of CCLM at staging, the incidence of early recurrence, and the survival benefit of hepatic metastectomy, more accurate determination of hepatic disease burden at staging and surveillance is needed. The clinical impact of improved radiologic accuracy should be assessed through randomized trials examining the impact of GA-enhanced liver MRI to conventional staging on recurrence-free and overall survival.

Acknowledgements

We wish to acknowledge support from the University of Wisconsin Institute for Clinical and Translational Research. Further, we wish to acknowledge GE Healthcare who provides research support to the University of Wisconsin. Finally, Dr. Reeder is a Romnes Faculty Fellow, and has received an award provided by the University of Wisconsin-Madison Office of the Vice Chancellor for Research and Graduate Education with funding from the Wisconsin Alumni Research Foundation.

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Figures

Incidence of CC by Stage and Incidence of Early and Late Recurrence: First column: incidence of CC by stage. Second column: incidence of early recurrence (recurrence < 12 months from curative intent surgery), by stage. For example, 50% of patients with resectable stage IV disease at diagnosis will have early recurrence. Third column: incidence of recurrence at 5 years. For example, 60-80% of patients with resectable stage IV disease at diagnosis will recur within 5 years.

Outline of stage-dependent incidence of CC, early recurrence, and potential MRI-based treatment changes. Assuming that early recurrence represents disease that was occult on staging imaging, the incidence of MRI-dependent treatment changes can be estimated. For example, Stage III patients have a reported incidence of early recurrence between 2-15%. Assuming an MRI sensitivity of 95%, MRI liver staging at diagnosis may have detected occult disease in 1 in 52 patients (assuming 2% early recurrence) or 1 in 7 patients (assuming 15% early recurrence).

Proc. Intl. Soc. Mag. Reson. Med. 29 (2021)

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