Prognosis of extracolonic findings on clinical computed tomographic colonography: A single-center experience.

Computed tomographic colonography (CTC) is less invasive than colonoscopy and barium enemas and has garnered significant attention in various large-scale clinical trials because of its potential utility in colorectal cancer screening and analysis [ 1 – 3 ]. CTC frequently determines extracolonic lesions, but the implications of these results for treatment plan modifications remain unclear. In the CT Colonography Reporting and Data System (C-RADS), these findings are categorized under the E category [ 4 ]. As a relatively new tool for colorectal investigation, CTC plays a growing role in clinical settings. In the European context, CTC is predominantly used for secondary assessments or follow-up examinations [ 5 ]. The United States Preventive Services Task Force, a key authority in preventive medicine, recommends grade-A colorectal screening for individuals aged 50–75 years every 5 years, with CTC considered a viable screening modality [ 6 ]. In Japan, CTC has been covered by insurance since 2012, but it is limited to cases with suspected colorectal malignancies. Furthermore, CTC is often used as an alternative screening tool for patients with positive fecal occult blood test results when colonoscopy is not feasible, providing an essential option for opportunistic screening and comprehensive colorectal assessment.

This study aimed to evaluate the clinical implications of extracolonic findings detected through CTC, specifically to determine the correlation between extracolonic lesions and prognosis in patients undergoing clinical CTC and to identify the association of such findings with their clinical trajectories.

The primary indications for examination included colorectal tumor (58%), gastric tumor (18%), gynecological disease (6%), incomplete endoscopy (5%), and other reasons (13%). Nonionic transvenous iodine-based contrast agents were used in 61% of the cases. Among the 103 cases (mean observation period [OP]: 2,183 days), the distribution in the Past E category was E1, E2, E3, and E4 in 18 (17%, mean OP: 2,821 days), 39 (38%, 2,759 days), 6 (6%, 2,150 days), and 40 (39%, 1,338 days), respectively ( Fig 1 ). Significantly, five E4 cases (5% of the total and 12.5% within E4) demonstrated incidental abnormalities unrelated to the primary disease, which had not been previously diagnosed. Among these, two cases (endometriosis with colonic adhesions and renal pelvic carcinoma) underwent surgical intervention and were pathologically confirmed (mean OP: 3,151 days). The remaining three cases (metastatic renal tumor, pelvic tumor, and abdominal aortic aneurysm) received no treatment because of disease progression (mean OP: 411 days). The distribution of patients in the Revised E category was 7 in E1 (7%, mean OP: 3,749 days), 44 in E2 (43%, mean OP: 2,633 days), 6 in E3 (6%, mean OP: 2,538 days), and 46 in E4 (45%, mean OP: 1,466 days) ( Table 1 ). The survival curves for the Past E and Revised E categories show differences in overall trends between category E4 showed a poor prognosis and the trends of the E2 and E3 curves intersected. The 5-year survival rates were 87%, 92%, 100%, and 48% for the Past E1, E2, E3, and E4 (p < 0.0001, log-rank test) categories and 100%, 90%, 80%, and 53% for the Revised E1, E2, E3, and E4 categories, respectively ( p < 0.0001, log-rank test). The survival curves showed differences in the E1 and E3 trends between the Revised E and Past E categories. Observation period (OP) refers to the time elapsed between the initial diagnosis and either the patient’s death or the last confirmed survival date in the medical records. In this study, the E4 category was observed more frequently in the general population. The mean OP was shorter for the E4 category than for the other categories. The concordance rate between the Past E and Revised E categories was high at 0.83 (95% confidence interval [CI]: 0.77–0.88), reflecting some discrepancies ( Table 2 ). In the cross-tabulation between the Past E and Revised E categories, a trend toward increasing categories was observed, with 16 cases showing an upward shift and five showing a downward shift due to re-evaluation. The most frequent change was from Past E1 to Revised E2, primarily due to the discovery of microcystic lesions and other minor findings. Additionally, six cases were reclassified from Past E1, E2, and E3 to Revised E4. The most frequent change was from Past E1 to Revised E2, primarily due to the discovery of microcystic lesions and other minor findings. Additionally, six cases were reclassified from Past E1, E2, and E3 to Revised E4. Moreover, 18 patients were referred for further examination due to Past E findings, including 4 with E2, 5 with E3, and 9 with E4 findings. These supplementary examinations included CT, MRI, PET-CT, cytology, and biopsy. No adverse events were associated with these examinations. Four patients were diagnosed with benign conditions in the case of E2 category findings. Meanwhile, five patients demonstrating Past E3 results underwent observational follow-up without any treatment intervention. None of the patients in the Past E2 or E3 categories required further examinations that necessitated changes to the treatment plan (mean OP for E2: 2,889 days; mean OP for E3: 2,976 days). Of the nine patients classified under the Past E4 category who were re-examined, six achieved a positive response to treatment, including complete surgical resection or partial response to chemotherapy (mean OP: 1,286 days). One of the nine patients who had an incidental discovery of an abdominal aortic aneurysm discovered was scheduled for treatment after management of the primary lesion but unfortunately died due to other causes before undergoing this treatment (OP: 162 days) ( Table 3 ). A positive response to treatment refers to a significant reduction in lesion size or complete resection of the lesion, either through surgical intervention or chemotherapy. Recurrence/metastasis refers to the reappearance of the primary tumor or its spread to other organs during the observation period. Scheduled for treatment but died refers to patients who had been diagnosed with conditions requiring treatment for abdominal aortic aneurysm but passed away before the planned treatment could be administered. The mean OP was 1,338 days for patients with Past E4 findings (n = 40) in terms of prognosis post-CTC, in contrast to 2,719 days for patients with combined Past E1, E2, and E3 results (n = 63). The results of Kaplan–Meier analysis revealed that patients in the Past E4 category (mean survival: 5.6 years) had a significantly worse prognosis ( p < 0.0001, log-rank test) compared to those with other extracolonic findings (mean survival: 10.1 years) across the remaining categories (E1, E2, and E3 combined) ( Fig 1 ). The hazard ratio was found to be 8.2 (95%CI: 3.7–18.4) for the Past E1, E2, and E3 categories combined compared with the Past E4 category. Within the Past E4 category, no significant difference in survival was observed between groups in which CTC was performed for the primary complaint of colorectal cancer (mean survival: 8.7 years) and groups with primary complaints other than colorectal cancer (mean survival: 8.0 years). The Revised E category also showed significant differences in prognoses between the E1, E2, and E3 categories (mean survival: 10.0 years) and the E4 category (mean survival:6.2) (p < 0.0001) ( Fig 2 ). The hazard ratio was 5.2 (95%CI: 2.4–11.2) for the Revised E1, E2, and E3 combined categories compared with the Revised E4 category. The Kaplan – Meier analysis comparing the combined E1, E2, and E3 categories with the E4 category revealed significant differences in the survival rates in the Past and Revised categories ( p < 0.0001, Log-rank test). The 5-year survival rates were 91% for past E1, E2, and E3 and 48% for past E4, compared with 90% for revised E1, E2, and E3 and 53% for revised E4.

Post-detection follow-up of extracolonic lesions in patients with E2 and E3 findings primarily involved exclusionary diagnoses without substantive treatment plan changes. The prognosis was worse for the patients with category E4 findings than for those with category E1, E2, and E3 findings among the extracolonic lesions detected during clinical CTC. Irrespective of the underlying disease, the E4 category finding is crucial in clinical CTC because it provides important guidance for clinicians and assists in the development of appropriate treatment plans.

This study was approved by our institutional review board, and written informed consent was obtained from all participants prior to their inclusion. A total of 103 patients underwent clinical CTC examinations at Gifu University Hospital between May 2012 and February 2013. The cohort consisted of 59 males (mean age: 67.3 years; range: 40–85 years) and 44 females (mean age: 66.9 years; range: 42–88 years). Clinical indication–based CTC examinations, including follow-up for suspected colorectal abnormalities, were performed. CTC was conducted following a complete colonoscopy using a 64-row multi-detector CT (750HD, GE Healthcare) without a tagging unit. Patients underwent plain or contrast-enhanced CT scans in prone or lateral and supine positions, with automatic exposure control set at a standard dose for preoperative assessments (supine and lateral noise index [NI] = 12 and supine NI = 10). An iodine dose of 600 mg/kg (Iomeron 350 mgI, Eisai Co., Ltd.) was administered over 30 s for contrast-enhanced CT. We used a bolus tracking method for the dynamic study. An automatic carbon dioxide insufflator (PROTOCO2L, EIDIA) was used to dilate the colon. Prone or lateral and supine images were acquired in a single breathhold. Image reconstruction used iterative reconstruction (ASiR 30%, GE Corporation) with a slice thickness of 1.25 mm and an interval of 1.25 mm without any gap for CTC. The CTC images were analyzed using an image workstation (Advantage workstation 4.2, GE Healthcare), and clinical reports were generated using diagnostic software (ShadeQuest, Yokokawa Medical). Four radiologists with varying levels of experience (one with 3 years, two with 4 years, and one with 14 years) participated in the readings. All readings were subsequently reviewed and confirmed by the most experienced radiologist, who had 14 years of experience and had conducted > 300 CTC examinations. All reports were investigated to identify extracolonic findings and categorized according to their respective E categories outlined in the C-RADS. Lesion descriptions, including those of lymph nodes and similar findings, were classified according to suspicion level. Findings of “possible” or higher were categorized as E4. Findings with lower suspicion levels were classified as E3. For the present study purpose, all CT images were re-evaluated to ensure greater accuracy in E-category classification. This review was independent of the E categories used in clinical practice. Additional re-evaluations were conducted between June and August 2024. Three gastrointestinal radiologists, with 6, 12, and 26 years of experience, respectively, reassessed the E categories for all extracolonic lesions to reach a consensus. For the sake of clarity throughout this paper, the clinically used E categories will be referred to as “Past E” and the re-evaluated ones will be referred to as “Revised E.” The patients’ electronic medical records were reviewed from the time of examination until treatment, follow-up, or death. The list of patients who provided consent was pseudonymized, ensuring linkable anonymity, and their prognoses and clinical outcomes were tracked through electronic medical records from December 29, 2023, to January 29, 2024. Analyses were performed to assess the effect of identifying lesions categorized as Past E2 or higher on changes to the treatment plan. We evaluated additional diagnostic examinations triggered by extracolonic findings on CTC, such as CT, magnetic resonance imaging (MRI), positron emission tomography-CT (PET-CT), biopsy, and cytology. Electronic medical records were used to track all examinations to evaluate their influence on the treatment strategy. We determined if complete surgical resection, any form of chemotherapy, or radiation therapy resulted in at least one instance of partial response or complete response. The treatment outcomes, specifically the ability to achieve a clinical response on the basis of extracolonic lesion identification, were confirmed by reviewing the patients’ clinical records and treatment histories.

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