Our research review identified 9 studies that described extracolonic findings in CT colonography in more than 100 consecutive research subjects, used a well-defined subject population, and included a categorization of gravity for the extracolonic findings (). Most studies defined significant extracolonic findings as imaging findings requiring further investigation, having an impact on the medical treatment the subject was receiving (based on the correlation of the findings with the subject’s symptoms or history), or requiring image-guided or operative treatment.
Incidental Extracolonic Findings in CT Colonography Research
In general, slightly more than half of research subjects in screening or asymptomatic populations had any type of extracolonic finding (median, 52 percent; weighted mean, 53 percent of research subjects).7
In contrast, when research subjects were comprised of symptomatic patient populations or patients with known colorectal disease, this frequency was higher (and could even be the large majority of subjects; median, 69 percent; weighted mean, 59 percent of research subjects).8
Across all studies, research subjects often had more than one IF. However, the frequency of extracolonic findings of potential medical significance was significantly less. Across CT colonography studies examining asymptomatic research subjects, the proportion of research subjects having a significant extra-colonic finding that necessitated further investigation or medical/surgical treatment was eight percent weighted average (median nine percent; range 5-11 percent), with the largest study of over 1200 patients having five percent of subjects with such findings.9
In studies examining symptomatic subjects, 16 percent (weighted average) of research subjects (median 17 percent; range 8-25 percent)10
had a significant extracolonic findings that necessitated further investigation or medical/surgical treatment. The number of subjects who underwent any subsequent type of medical or surgical intervention was highly variable, ranging from 1.3-2.3 percent in asymptomatic subject groups11
to 6-19 percent in symptomatic subject groups.12
The mean for both groups was 7.8 percent (SD 6.3 percent). Very few subjects in the asymptomatic population underwent surgery as result of identification of IFs (<2.3 percent).13
This percentage was higher (up to 15 percent) in the symptomatic population.14
While the mean cost for the work-up of IFs appears minimal on a per-subject basis (approximately $25-$34, based on Medicare reimbursement rates), these estimates do not include the therapeutic cost of treating the discovered abnormality (e.g., nephrectomy for renal cell carcinoma). Moreover, the financial burden incurred from the work-up and treatment of extracolonic findings can be significant for any individual. For example, one prominent radiologist underwent a CT colonography exam that resulted in negative colonic findings, but identified multiple indeterminate extra-colonic findings. He then underwent multiple investigations to elucidate the nature of these indeterminate imaging findings, including two invasive procedures (a thoracoscopy and a liver biopsy). None of these additional tests or procedures resulted in the identification of a serious or acute disease, but his health care costs exceeded $50,000 and included in-hospital recovery time.15
The medical importance of even extracolonic findings categorized as “significant” — that is, those for which most physicians would agree that further investigation or medical/surgical intervention is needed — can be highly variable. Some findings reported as highly significant will eventually prove medically insignificant after further work-up is performed. Some of the most common significant IFs, such as renal cell carcinomas or large abdominal aortic aneurysms, are easily treatable with clear benefit to the subject. However, the impact of discovering an advanced cancer (to which the subject will eventually succumb) is less clear, e.g., a patient with an advanced lung cancer that is detected at a late stage (). In this instance, research CTC exams result in lead time bias (i.e., the screening test detects a disease before it is symptomatic, but this earlier identification and treatment of the disease does not result in change in outcome or time of death).
Figure 1 69-year-old male ex-smoker with a history of pulmonary fibrosis underwent CT colonography for research purposes. The transverse image of the lower chest shows a large pulmonary nodule with cavitation (arrow). The biopsy demonstrated multifocal squamous (more ...)
CT colonography research exams can detect some early cancers that can be treated at curable stages (). A recent meta-analysis examined the identification of early cancers (i.e., surgically resectable cancers without nodal or distant metastases) across published colonography studies, and found that such cancers were identified in 0.9 percent of research subjects (or 0.6 percent, when excluding elderly and frail patients who likely could not undergo curative surgery because of comorbid conditions),16
and noted that this frequency is similar to the 0.7 percent estimated frequency of limited (i.e., non-metastatic) colon cancers detected by colonoscopy in asymptomatic adults.17
Figure 2 50-year-old asymptomatic male with no comorbidities underwent CT colonography for research purposes. The transverse image of the abdomen shows incidentally noted mesenteric adenopathy (arrows pointing to enlarged lymph nodes). The colon itself was negative (more ...)
The study of 1253 asymptomatic subjects we included in our review discovered eight cases of unsuspected extracolonic malignancy (one case per 200; 0.6 percent).18
Similarly, Thomas Gluecker et al. reported uncovering at least seven unsuspected neoplasms in a healthy screening population of 681 subjects (one percent).19
Amy Hara et al. reported discovering two renal cell carcinomas that necessitated curative surgery in a smaller screening sample (264 patients).20
While research CTC may discover extracolonic malignancies at an early (treatable) stage, the CT colonography imaging technique does not permit detection and characterization of all intra-abdominal pathologies. This is because research CTC exams generally employ a low radiation dose without intravenous contrast, while clinical abdominal CT exams generally use a standard radiation dose and intravenous contrast. Hara et al.21
reported that 12.5 percent (3/24) of subjects undergoing research CTC had extracolonic findings that were radiographically occult (i.e., not detectable) on their low-dose, non-contrast research CTC exam, but which were subsequently seen on normal-dose, contrast-enhanced CT done within one year. Changes in acquisition techniques therefore directly affect the number and type of significant IFs referred for further evaluation. Adrian Spreng et al. examined symptomatic subjects referred for colonos-copy using normal radiation doses and intravenous contrast in some CTC exams.22
He found that with these changes in acquisition technique and in his subject population, the proportion of subjects with IFs was very large (75 percent) and that nearly one-fifth of subjects underwent treatment for an extracolonic finding.23
Consequently, research subjects need to be informed of the potential for significant extracolonic findings according to the type of exam they are undergoing, and should be cautioned that imaging of the abdomen and pelvis may not reveal all abnormalities.
While the clinical import of many significant extracolonic findings is understood (e.g., abdominal aortic aneurysms or lymphomas), there are many findings such as lung nodules, ovarian masses, and low-attenuation masses in solid organs that are indeterminate in nature, thus requiring further imaging or surveillance (Figures and ).24
In addition, most grading schemes for the severity of extracolonic findings include a “medium” significance category in which the import of an IF depends upon the clinical symptom-atology (e.g., gallstones, kidney stones, hiatal hernia of the stomach, and diverticulosis of the colon). Extracolonic findings in the musculoskeletal system are rare and usually clinically insignificant, except for the rare spondylolysis or unsuspected osseous metastases.25
The frequency of IFs in CT colonography research is similar to the frequency in other studies using unenhanced CT of the abdomen and pelvis.26
Figure 3 57-year-old asymptomatic female with no comorbidities underwent CT colonography for research purposes. The transverse image of the abdomen shows 4 cm cystic adnexal structure in the pelvis. The colon itself was negative for any precancerous lesions. Following (more ...)
Figure 4 73-year-old asymptomatic male with no comorbidities underwent CT colonography for research purposes. The transverse image of the abdomen shows incidentally found 3.3 cm aortic aneurysm. The primary physician was communicated, and the patient was advised (more ...)
Radiologists have developed a formal classification system for extracolonic findings in patients undergoing CT colonography for their own health care (i.e., not research subjects).27
The Virtual Colonoscopy Working Group proposed a reporting system (CRADS) with five categories named E0 through E4 in increasing order of clinical importance. The E0 category includes exams in which evaluation of extracolonic abnormalities is severely limited by imaging artifacts. E1 denotes normal extracolonic structures or normal anatomic variants, and E2 encompasses findings that do not merit further work-up or management (). Examples of E2 include simple liver or renal cysts, vertebral hemangiomas, and asymtopmatic cholilithiasis. While E0, E1, and E2 correspond to imaging findings of low medical significance, E3 is used for findings of indeterminate significance such as a complex renal cyst. Findings of indeterminate significance are findings, which are probably (but not definitively) benign, and for which further work-up or treatment might occur at the discretion of the patient and her physician. All potentially important findings are classified in the E4 category, including solid renal masses, lymphadenopathy, aortic aneurysms, and non-uniformly calcified pulmonary nodules greater than or equal to 1 cm. The effects of C-RADS categorization were recently reported by two practices, one reporting that the incidence of E4 lesions was 2.2 percent,28
and the other reporting a significant difference in the frequency of E4 lesions between screening and non-screening populations (with the former having more).29
57-year-old asymptomatic male underwent CT colonography for research purposes. The transverse image of the abdomen shows a 6.5 cm simple renal cyst that was categorized as an insignificant finding. No follow-up was recommended.
We also reviewed the literature on whether potentially significant extracolonic findings are communicated to subjects or their primary care physicians. Perry Pickhardt et al. did not relay IFs directly to subjects, but communicated such findings to their primary care physicians.30
Judy Yee et al. also notified the primary care physician by telephonic communication, but no official report was generated.31
Similarly, Hara et al. communicated by sending letters notifying the primary care physician when a highly important lesion was found and wrote a formal CT report.32
While it may appear unusual that CTC researchers have reported contacting subjects’ physicians rather than subjects themselves, a report by Giovanni Casola and colleagues presented at the Fourth International Symposium on Virtual Colonoscopy exposed the potential for subjects to ignore or delay the work-up of significant IFs if primary care physicians are not contacted.33
Casola et al. reviewed clinical radiology reports from a group of 1200 self-referred patients who paid out-of-pocket expenses for a screening body CT at a whole-body screening center. These patients had CT reports mailed to them. Casola et al. counted reports that identified “indeterminate or suspicious findings for malignancy” or findings “highly suggestive of malignancy or life-threatening condition” and contacted these patients five years later.34
Nearly one-third of patients were unaware of their worrisome CT findings from five years before, suggesting that many of these patients never pursued medical consultation or follow-up of worrisome findings. Considering the potentially life-threatening consequence of at least some of these findings, it appears that leaving the evaluation of these lesions to the discretion of the subject (who may be unaware of their gravity or speed with which the finding should be pursued) is problematic.
Survey of CT Colonography Research Programs
To study how CTC research programs have handled IFs, we surveyed by e-mail the CTC researchers presenting during the plenary session of the 5th Annual Virtual Colonoscopy Symposium (October 2004, n=25). Speakers at the plenary sessions of this conference generally represented academic medical centers with large, active research programs in colonography. Ten principle investigators (7 U.S.; 3 European) or their study coordinators (n=2; both U.S.) responded to the survey. All research programs (12/12; 100 percent) reported having a radiologist examine every CT dataset for potentially significant extracolonic findings, 92 percent (11/12) on the same day that the CT research exam is performed. A slight majority (7/12; 58 percent) reported all extracolonic findings, whereas 42 percent (5/12) reported only potentially significant extracolonic findings. The mechanism of conveying extracolonic findings varied widely, and a slight majority (7/12; 58 percent) reported using two or more methods to relate potentially significant extracolonic findings to research subjects and/or their physicians. Eighty-three percent (10/12) of researchers generated a clinical report to detail extracolonic findings, with slightly less (8/12; 67 percent) contacting the subject’s physician directly (by letter 3/12, 25 percent; or phone/fax 5/12, 42 percent). Forty-two percent (5/12) of researchers contacted the subject directly. Thirty-three percent (4/12) of studies generated only a clinical report.
In contrast to what the patient was told verbally during the consent process, only 42 percent (5/12) of researchers reported that their written consent form told subjects if and when extracolonic findings would be reviewed, and only 17 percent (2/12) of consent forms told subjects how potentially significant extracolonic findings would be reported to them.
All but one institution (11/12; 92 percent) discussed the potential for discovering incidental (extracolonic) findings of medical significance verbally during the informed consent process. Seventy-five percent (9/12) of researchers discussed the potential for needing extra medical tests to address IFs discovered, while a similar number discussed the non-specificity of image findings at CT colonography (explaining that further testing or imaging could be necessary). In contrast to what the patient was told verbally during the consent process, only 42 percent (5/12) of researchers reported that their written consent form told subjects if and when extracolonic findings would be reviewed, and only 17 percent (2/12) of consent forms told subjects how potentially significant extracolonic findings would be reported to them. Only one of the researchers surveyed reported that studying extracolonic findings was a primary aim of his research colonography studies.