Diagnosis Of Recurrent Colorectal Cancer Research Articles

Combined 18-FDG-PET/Contrast-Enhanced CT in the Diagnosis of Recurrent Colorectal Cancer: A Prospective Monocentric Pilot Study

Contrast-enhanced CT scan and 18DG-PET are used in the staging and surveillance of Colorectal Cancer (CRC). We here evaluate the feasibility and performances of systematically combining 18-FDG-PET and contrastenhanced CT whether as a stand-alone diagnostic examination, or as 2 separate examinations, for the early detection of recurrent colorectal cancer. 45 patients underwent 159 planned diagnostic follow-up sessions: 109 (68%) were performed as a combined modality during the same examination and 50 were performed as two separate examinations and acquired at different timepoints. Fourteen patients experienced recurrence during the study period. The sensitivity of 18-FDG-PET and contrast-enhanced CT scan in detecting a recurrent disease was 84.4% and 86.6 % respectively with a specificity of 96% and 97% respectively. 18-FDG-PET and contrast-enhanced CT findings’ were concordant in 79% of cases. The overall sensitivity and specificity in detecting CRC recurrence were 80% and 99% respectively in the combined procedure and 89% and 98% respectively in the two-time procedure. The positive predictive value of the procedure (combined or two-time procedure) for the detection of recurrent CRC was 100% with, however a shorter delay for decision with the combined [7.7 vs. 12.2 days] (p<0.05). The combined procedure is feasible in almost 2/3 of cases. When compared to the two-time procedure, it is performant in detecting recurrent CRC with shorter delay to therapy.

Evaluation of Circulating Tumor DNA for Methylated BCAT1 and IKZF1 to Detect Recurrence of Stage II/Stage III Colorectal Cancer (CRC).

Most recurrences of early-stage colorectal cancer detected with current surveillance measures are widespread and incurable. Circulating tumor DNA (ctDNA) may facilitate earlier diagnosis of recurrent colorectal cancer and improve cancer-related outcomes. Plasma from patients undergoing standard surveillance after definitive treatment for stage II/III colorectal cancer was assayed with COLVERA and carcinoembryonic antigen (CEA) at a single time point. Results were correlated with radiographic imaging. Assay performance, including sensitivity and specificity for recurrence, were compared. Impact of potentially confounding variables was also explored. 322 patients were included in the final analysis, and 27 recurrences were documented over a median follow-up period of 15 months. Sensitivity for recurrence was 63% [confidence interval (CI), 42.4-80.6] and 48% (CI, 28.7-68.1) for COLVERA and CEA (≥5 ng/mL), respectively (P = 0.046), while specificity was 91.5% (CI, 87.7-94.4) and 96.3% (CI, 93.4-98.1), respectively (P = 0.016). Smoking and age were independent predictors of CEA but not COLVERA positivity. COLVERA was more sensitive but less specific than CEA in detecting recurrent colorectal cancer. Short median follow-up may have been responsible for apparent false positives in COLVERA. Studies with serial sampling and longer follow-up are needed to assess whether earlier detection of colorectal cancer recurrence translates into clinical benefit. This prospective study showed that COLVERA (a two-gene ctDNA assay) was more sensitive for detection of recurrence in a cohort of patients undergoing surveillance after definitive therapy for stages II and III colorectal cancer.

Diagnostic value of (18)F-FDG PET/CT as first choice in the detection of recurrent colorectal cancer due to rising CEA.

BackgroundThe diagnostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) as the first imaging approach in the evaluation of rising carcinoembryonic antigen (CEA) is not clear. The objective of this study was to investigate the value of 18F-FDG PET/CT in patients with colorectal cancer (CRC) and suspected recurrence based on rising CEA.MethodsA total of 73 patients with CRC were referred to PET/CT after radical surgery. Generally, all patients were scheduled to follow a CT-based post-surgical follow-up regimen. In the case of rising CEA, 18F-FDG PET/CT was performed in most patients with contrast-enhanced CT. The PET/CT images were independently reviewed by two readers. The presence or absence of recurrence was based on histology and/or standardized clinical follow-up.ResultsAmong 35 patients who had confirmed recurrence of CRC, PET/CT demonstrated recurrence with a sensitivity of 85.7 %, a specificity of 94.7 %, a positive predictive value of 93.8 %, and a negative predictive value of 87.8 %. The SUVmax ranged from 1.3 to 19.9. The mean time since the last postoperative imaging and PET/CT was 8 months (median 4 months). CEA values at referral ranged from 1.5 to 164.0 μg/L (median 5.6 μg/L). The diagnostic properties of PET/CT were analyzed in subgroups of patients with a single rising CEA sample (30 patients, 41 %), 31 patients (43 %) with two or more consecutive increases, and 12 patients (16 %) with persistently elevated values.Conclusions18F-FDG PET/contrast-enhanced CT has high diagnostic accuracy in the diagnosis of recurrent CRC, even in patients in a conventional CT-based follow-up program.

Does CEA and CA 19-9 combined increase the likelihood of 18F-FDG in detecting recurrence in colorectal patients with negative CeCT?

The purpose of this prospective study was to investigate the role of 2-(fluorine-18)-fluoro-2-deoxy-D-glucose ((18)F-FDG) PET/computed tomography (CT) in the diagnosis of recurrent colorectal cancer (CRC) in patients with increased tumor markers and negative contrast-enhanced computed tomography (CeCT) results. Forty-three patients (27 male; median age 66 years, range 31-93 years) with increasing tumor markers and negative CeCT during follow-up for treated CRC underwent (18)F-FDG PET/CT examinations. The serum values of carcinoembryonic antigen (CEA) (n=29) and CA 19-9 (n=20) were normal after completion of treatment, with subsequent increasing concentrations. Among the 43 patients, (18)F-FDG PET/CT was true positive in 32 (74.4%), false positive in two (4.7%), false negative in one (2.3%), and true negative in eight (1%) patients. On the patient-basis analysis, (18)F-FDG PET/CT had a sensitivity of 97% (confidence interval: 0.82-0.99), a specificity of 80% (0.44-0.96), a positive predictive value of 94% (0.78-0.98), and a negative predictive value of 88% (0.5-0.99). There was no statistically significant correlation between CRC recurrence and CEA and CA19-9 levels (P=0.561 and 0.55, respectively). Only in the group of patients (n=6) with both tumor markers increased did (18)F-FDG PET/CT have 100% accuracy in revealing recurrent disease. (18)F-FDG PET/CT is highly sensitive in the diagnosis of recurrent CRC in patients with increasing levels of tumor markers and negative CeCT regardless of the type or level of tumor marker; however, the combination of elevated CEA and CA 19-9 increases the likelihood of (18)F-FDG in detecting recurrence.

A role of 18F-fluorodeoxyglucose positron emission/computed tomography in a strategy for abdominal wall metastasis of colorectal mucinous adenocarcinoma developed after laparoscopic surgery

Metastasis to the abdominal wall including port sites after laparoscopic surgery for colorectal cancer is rare. Resection of metastatic lesions may lead to greater survival benefit if the abdominal wall metastasis is the only manifestation of recurrent disease. A 57-year-old man, who underwent laparoscopic surgery for advanced mucinous adenocarcinoma of the cecum 6 years prior, developed a nodule in the surgical wound at the lower right abdomen. Although tumor markers were within normal limits, the metastasis to the abdominal wall and abdominal cavity from the previous cecal cancer was suspected. An abdominal computed tomography scan did not provide detective evidence of metastasis. 18F-fluorodeoxyglucose positron emission/computed tomography (18F-FDG PET/CT) was therefore performed, which demonstrated increased 18F-fluorodeoxyglucose uptake (maximum standardized uptake value: 3.1) in the small abdominal wall nodule alone. Histopathological examination of the resected nodule confirmed the diagnosis of metastatic mucinous adenocarcinoma. Prognosis of intestinal mucinous adenocarcinoma is reported to be poorer than that of non-mucinous adenocarcinoma. In conclusion, this case suggests an important role of 18F-FDG PET/CT in early diagnosis and decision-making regarding therapy for recurrent disease in cases where a firm diagnosis of recurrent colorectal cancer is difficult to make.

Performance of integrated FDG PET/contrast-enhanced CT in the diagnosis of recurrent colorectal cancer: Comparison with integrated FDG PET/non-contrast-enhanced CT and enhanced CT

The aim of our study was to evaluate the accuracy of integrated positron emission tomography and computed tomography (PET/CT) using (18)F-fluorodeoxyglucose (FDG) with IV contrast for depiction of suspected recurrent colorectal cancer and to assess the impact of PET/contrast-enhanced CT findings on clinical management compared with PET/non-contrast-enhanced CT and CT component. One hundred seventy patients previously treated for colorectal cancer underwent PET/CT consisting of non-enhanced and contrast-enhanced CT for suspected recurrence. PET/contrast-enhanced CT, PET/non-contrast-enhanced CT and enhanced CT were interpreted by two experienced radiologists by consensus for each investigation. Lesion status was determined on the basis of histopathology, radiological imaging and clinical follow-up for longer than 6 months. Patient-based analysis showed that the sensitivity, specificity and accuracy of PET/contrast-enhanced CT were 93.2 (69/74), 95.8 (92/96) and 94.7% (161/170), respectively, whereas those of PET/non-contrast-enhanced CT were 89.2 (66/74), 94.8 (91/96) and 92.4% (157/170), respectively, and those of enhanced CT were 79.7 (59/74), 93.8 (90/96) and 87.6% (149/170), respectively. Sensitivity and accuracy differed significantly among the three modalities (Cochran's Q test: p = 0.0004 and p = 0.0001, respectively).The findings of PET/contrast-enhanced CT resulted in a change of management for 64 of the 170 patients (38%) and had an effect on patient management in 12 patients (7%) diagnosed by enhanced CT alone and 4 patients (2%) diagnosed by PET/non-contrast-enhanced CT. Integrated PET/contrast-enhanced CT is an accurate modality for assessing colorectal cancer recurrence and led to changes in the subsequent appropriate therapy.

PET/CT detects abdominal wall and port site metastases of colorectal carcinoma

Abdominal wall metastases from colorectal cancer (CRC) may be resected with curative results. Such lesions, often indicators of additional intra-abdominal lesions, may appear in surgical scars, stomas and port site metastases after laparoscope-assisted surgery (LAS). Post-operative changes, primarily surgical scars, alter local physical findings making early detection of small lesions challenging. The purpose of this study was to retrospectively evaluate the contribution of PET/CT to the diagnosis of recurrent colorectal cancer in the post-operative abdominal wall. 120 patients were referred for PET/CT with suspected recurrent CRC based on clinical, radiological or laboratory findings. All underwent whole body PET/CT imaging. 12 of these 120 (10%), were found to have abdominal wall lesions. A total of 16 abdominal wall lesions were detected, located to surgical scars, stomas, drain and laparoscope ports. Additional findings on PET/CT in this group included liver metastases, intra-abdominal lesions and retroperitoneal lymph node involvement. In general, the patients in this small group were young with high grade tumours presenting in advanced stages. In conclusion, PET/CT appears to be a sensitive tool for the diagnosis of abdominal wall recurrence of CRC. The accuracy of localization afforded by the fused functional and anatomic images makes PET/CT a likely tool for diagnosing abdominal wall lesions, including port site metastases of other aetiologies.

CEA, CA 242, CA 19-9, CA 72-4 and hCGβ in the Diagnosis of Recurrent Colorectal Cancer

Objective: The purpose of this study was to compare the utility of serum CEA, CA 19-9, CA 242, CA 72-4 and human chorionic gonadotropin (hCG)β in the follow-up of 102 surgically treated colorectal cancer patients, out of which 40 patients developed clinical recurrence. Methods: In patients with recurrent disease, serum samples were obtained at the time of clinical recurrence, and in the disease-free group, they were obtained postoperatively. The combined use of the markers was evaluated with logistic regression analysis. The sensitivities of the different tumour markers at various specificity levels were compared by receiver operating characteristic (ROC) curve analysis. Results: When the five tumour markers, Dukes stage and location of the primary tumour were evaluated together in the same model, only CEA provided significant diagnostic information (p < 0.0005) in addition to the location of the primary tumour (p = 0.003). The diagnostic information provided by the other serum tumour markers was insignificant, although CA 72-4 approached borderline significance (p = 0.053). ROC curves were constructed and the difference in the values of the area under the curve (AUC) between the different serum tumour markers was determined at the time of clinical recurrence. Of the individual markers, the highest AUC was observed for CEA (AUC = 0.931). The difference in AUC values between CEA and the other tumour markers was highly significant (p ≤ 0.001). Conclusions: CEA had the highest diagnostic accuracy in detecting recurrent colorectal cancer. Inclusion of CA 19-9, CA 242, CA 72-4 or hCGβ in the model did not improve the accuracy, although CA 72-4 approached borderline significance (p = 0.053). Thus, CEA seems to retain its position as the surveillance marker of choice for patients surgically treated for colorectal cancer.

15. Sensitivity of FDG CDET (2D Dual-Head Coincidence Gamma Camera) for the Detection of Occult or Doubtful Recurrences of Colorectal Cancer: Histopathological Correlation

Purpose: The aim of this study was to evaluate the efficacy of FDG-CDET for the detection of recurrences of colorectal cancer, in occult disease or in doubtful cases at conventional imaging (CI). In all the evaluated cases, the result of FDG-CDET was compared with post surgical histology both on patient and on site bases.Methods and patients: After fasting for 6h or more, 150-250 MBq of 18F-FDG were injected i.v. and 2D imaging (whole-body scan and at least a tomoscintigram) was started 45 min. later, using a PICKER CDET gamma camera. Among the 214 examinations (ex) performed for detection of recurrences of colorectal cancer between Jul 1997 and Feb 2000, we only considered the 58 cases with negative or questionable CI and a post surgical histologic proof.Results: Patients were referred in three different contexts:1. suspicion of recurrence (SR) due to raising CEA levels with normal CI i.e. occult disease (18 ex: 13 TP, 3 FN, 2 FP on patient basis, 17 TP, 9 FN, 4 FP on site basis)2. SR due to equivocal image(s) at follow-up CI (25 ex: 18 TP, 5 FN, 2 TN on patient basis, 21 TP, 10 FN, 2 TN on site basis)3. SR due to both raising CEA levels and equivocal CI (15 ex: 13 TP, 2 FN on patient basis, 16 TP, 8 FN, 3 TN, 1 FP on site basis).4. The overall sensitivity was 44/54 = 81% on patient basis and 54/81 = 67% on site basis. Specificity could not be evaluated because of the very small number of patients re-operated in case of negative FDG-CDET.5. Conclusion: When conventional imaging could not contribute, i.e. a sensitivity of zero by definition, FDG-CDET accurately diagnosed a recurrence in 81% of the patients and located 67% of all recurrent lesions. These results confirm, with post surgical histology as the only gold standard, that FDG-CDET is a powerful tool for diagnosis of recurrent colorectal cancer in difficult cases. It could be used as the first line examination as soon as a recurrence is suspected, in order to avoid less contributive imaging procedures.

Effect of radioimmunoscintigraphy on the management of recurrent colorectal cancer.

Radioimmunoscintigraphy (RIS) is being used increasingly as a new investigation in the diagnosis of recurrent colorectal cancer. This study assessed the efficacy of 99mTc-radiolabelled PR1A3 scanning in a cohort of patients with possible recurrent colorectal cancer and the effects of scan interpretation on subsequent clinical management. The scans and case notes of patients scanned over a 3-year period were reviewed. Forty-seven scans in 40 patients were available for analysis. In 39 instances in which scan interpretation could be verified accurately, sensitivity for recurrent colorectal cancer was 22 of 23 (96 per cent), specificity for recurrent colorectal cancer was eight of 16 (50 per cent), positive predictive value for recurrence was 22 of 30 (73 per cent) and negative predictive value for recurrence was eight of nine (89 per cent). In 16 of the 40 patients, scan interpretation strengthened a management decision or altered management. This was beneficial to ten patients and possibly detrimental to six. This study demonstrated that RIS is sensitive in the detection of recurrent colorectal cancer and benefited the patient in one-quarter of cases. For the majority of patients, accurate detection of recurrent disease cannot be followed by curative therapy, but there is an important subgroup of patients in whom RIS alters management beneficially. However, a randomized prospective study is needed to confirm this.

The use of biliary CEA measurements in the diagnosis of recurrent colorectal cancer

To assess the usefulness of biliary CEA determinations in the diagnosis of recurrent tumour, gallbladder bile was sampled in patients who underwent laparotomy for proven or suspected recurrent colorectal cancer and in control patients. Biliary CEA concentrations in controls were < 5 ng/ml, whereas significantly elevated CEA concentrations were found in the bile of all patients with tumour recurrence. Serum concentrations in these patients were elevated in 77% only. In a series of 12 patients with (a) suspicious lesion(s) on liver imaging but normal serum CEA concentration during follow-up, biliary CEA determination differentiated clearly between metastases and benign lesions. Biliary CEA determination seems to aid detection of tumour recurrence at an early stage and may preclude unnecessary surgery in patients with undefined liver lesions.

Value of radioimmunoscintigraphy with technetium-99m labelled anti-CEA monoclonal antibody (BW431/26) in the detection of colorectal cancer

This study was undertaken as part of a Coordinated Research Programme initiated by the International Atomic Energy Agency to evaluate the usefulness of radioimmunoscintigraphy (RIS) in the management of patients with colorectal cancer. Technetium-99m labelled BW431/26, a monoclonal antibody against carcinoembryonic antigen (CEA), was used. The study included 73 patients (31 females and 42 males). Sixty-eight patients were suspected of having recurrent colorectal adenocarcinoma while another five were suspected to have primary colorectal cancer. Images were acquired at 10 min and 4 and 24 h following the injection of radioantibody. The efficacy of RIS in tumour detection was evaluated by the findings at surgery, histological investigation and/or other diagnostic modalities and clinical follow-up. Four of five patients with suspected primary colorectal cancer gave true-positive results (three at primary sites, one at the site of a metastatic lesion) while one was false-positive. The overall accuracy of RIS in the diagnosis of recurrent colorectal cancer was 87%. Its sensitivity in the detection of locoregional or abdominal recurrence and liver metastases was 97% and 89% respectively. RIS was more accurate than computed tomography (CT) scan in the detection of pelvic recurrence and liver metastases while CT scan was far superior to RIS in detecting lung metastases. RIS proved most useful in patents who had rising CEA levels on clinical follow-up but in whom other work-up, including CT scan, was negative. The advantages of RIS include the ability to detect tumour recurrence prior to other investigations and to identify tumour recurrence in areas such as the pelvis, where CT and magnetic resonance imaging have their greatest weaknesses in diagnosing recurrent disease. The imaging accuracy is significantly increased when combined CT and antibody imaging is performed.

Contribution of PET in the diagnosis of recurrent colorectal cancer: comparison with conventional imaging

The clinical value of total body PET with FDG was evaluated in 76 patients presenting with or suspected of recurrent local or distant colorectal cancer. PET results were compared to those of routine imaging (CT pelvis, CT/US liver and CXR). The accuracy of PET for local disease was 95% which was superior to CT-pelvis (accuracy 65%). PET accuracy for liver metastases (98%) compared favourably to CT/US-liver accuracy (93%). Unexpected extra-hepatic mestastases were detected by PET in 14 locations in 10 patients. Also, a primary breast cancer was found in one patient. The main value of PET appeared an improved staging of apparently resectable, local or distant recurrent disease. Thereby, a more adequate indication of major secondary surgery could be attained.