Clinical value of 18F-FDG PET/CT in assessing suspicious relapse after rectal cancer resection

Abstract

AIM: To evaluate the value of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in the restaging of resected rectal cancer.

METHODS: From January 2007 to Sep 2008, 21 patients who had undergone curative surgery resection for rectal carcinoma with suspicious relapse in conventional imaging or clinical findings were retrospectively enrolled in our study. The patients underwent 28 PET/CT scans (two patients had two scans, one patient had three and one had four scans). Locoregional recurrences and/or distant metastases were confirmed by histological analysis or clinical and imaging follow-up.

RESULTS: Final diagnosis was confirmed by histopathological diagnosis in 12 patients (57.1%) and by clinical and imaging follow-up in nine patients (42.9%). Eight patients had extrapelvic metastases with no evidence of pelvic recurrence. Seven patients had both pelvic recurrence and extrapelvic metastases, and two patients had pelvic recurrence only. ¹⁸F-FDG PET/CT was negative in two patients and positive in 19 patients. ¹⁸F-FDG PET/CT was true positive in 17 patients and false positive in two. The accuracy of ¹⁸F-FDG PET/CT was 90.5%, negative predictive value was 100%, and positive predictive value was 89.5%. Five patients with perirectal recurrence underwent ¹⁸F-FDG PET/CT image guided tissue core biopsy. ¹⁸F-FDG PET/CT also guided surgical resection of pulmonary metastases in three patients and monitored the response to salvage chemotherapy and/or radiotherapy in four patients.

CONCLUSION: ¹⁸F-FDG PET/CT is useful for evaluating suspicious locoregional recurrence and distant metastases in the restaging of rectal cancer after curative resection.

Key Words: ¹⁸F-fluorodeoxyglucose, Positron emission tomography/computed tomography, Rectal cancer, Follow-up, Restaging, Locoregional recurrence, Distant metastases

INTRODUCTION

Rectal cancer is one of the most common malignancies in the United States and one of the most frequent causes of cancer-related death[1]. The incidence of rectal cancer is rapidly increasing with changes in life styles and diets and is thus an emerging health issue in the Asian region, including Korea, Japan and China[2,3]. Over the past decade, significant progress has been made in the treatment of localized rectal cancer by advances in surgery, radiotherapy, and chemotherapy. However, distant metastasis and local recurrence continues to be a major problem following treatment of rectal cancer, and carries an extremely poor prognosis[4,5]. More importantly, distant metastasis and locoregional recurrence are seldom curable and produce debilitating symptoms that are difficult to palliate.

Endoscopic examination, conventional computed tomography (CT), and magnetic resonance imaging (MRI) are the main techniques used to follow-up of resected rectal cancer[6,7]. However, these techniques may be not reliable for detecting local recurrence and distant metastasis[8]. The reported increase in sensitivity of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) over CT and MRI has been attributed to the ability of ¹⁸F-FDG PET to detect metabolic abnormalities that precede the morphological changes seen by CT[9]. The whole body imaging of the ¹⁸F-FDG PET/CT study also contributes to the increased sensitivity through detection of distant metastatic lesions[10]. This study was undertaken to further define the utility of ¹⁸F-FDG PET/CT imaging in evaluating suspicious locoregional recurrence and distant metastases in the restaging of resected rectal cancer.

MATERIALS AND METHODS

Patients

In the period from January 2007 to July 2008, 21 patients (14 males and 7 female; age range, 27-78 years; mean age, 58.3 years), who had undergone curative surgery resection for rectal carcinoma and who had suspicious local recurrence and/or distant metastasis in conventional imaging or clinical findings, were retrospectively enrolled in our study. Twenty-one patients underwent 28 PET/CT scans (2 patients had two scans, one patient had three scans and one patient had four scans). The standard of reference for tumor recurrence consisted of histopathological confirmation or clinical and imaging follow-up information for at least 11 mo after PET/CT examinations.

¹⁸F-FDG PET/CT technique

The patients were asked to fast for at least four hours before undergoing ¹⁸F-FDG PET/CT to ensure that their blood glucose level was within the normal range (70-120 mg/dL) prior to intravenous injection of ¹⁸F-FDG. The patients received an intravenous injection of 370-666 MBq (10-18 mCi) of ¹⁸F-FDG. Data acquisition by an integrated PET/CT system (Discovery STE; GE Medical Systems, Milwaukee, WI, USA) was performed within 60 min after injection. The procedure of data acquisition was as follows: CT scanning was performed first, from the head to the pelvic floor, with 110 kV, 110 mA, a tube rotation time of 0.5 s, a 3.3-mm section thickness, which was matched to the PET section thickness. Immediately after CT scanning, a PET emission scan that covered the identical transverse field of view was obtained. Acquisition time was three minutes per table position. PET image data sets were reconstructed iteratively by applying the CT data for attenuation correction, and coregistered images were displayed on a workstation.

PET/CT image interpretation

Reviewer 1 and reviewer 2, who were aware of other clinical or imaging information, read the ¹⁸F-FDG PET/CT images on a high-resolution computer screen. The reviewers reached a consensus in cases of discrepancy. Reviewer 1 had 20 years of experience in both nuclear medicine and radiology, and reviewer 2 had 5 years of experience in both nuclear medicine and radiology. On the basis of knowledge of the normal biodistribution of ¹⁸F-FDG, lesions were identified as foci with increased tracer accumulation relative to that in comparable normal contralateral structures and surrounding soft tissues. The lesions were qualitatively graded as definitely or probably abnormal (categorized as representing a tumor) if the accumulation of ¹⁸F-FDG was markedly to moderately increased. Diffuse mildly increased activity or no increased activity (in the case of an abnormality identified on CT for which no corresponding abnormality was present on PET) was considered to be normal or benign disease.

RESULTS

Clinical presentation of recurrent disease

Mean time after treatment to PET/CT exam was 17.1 mo (1-51 mo) and mean follow up time after PET/CT exam was 11 mo (1-19 mo). At the time of recurrent rectal cancer being suspected, the mean patient age was 58.3 years with a tendency towards male gender distribution (66.7%). Suspicious locoregional recurrence and distant metastasis for examination with ¹⁸F-FDG PET/CT were an unexplained increase in carcinoembryonic antigen values (CEA) (n = 4), unexplained anal pelvic pain (n = 3), suspected pelvic recurrence and distant metastases at CT and MRI (n = 7), suspected pelvic recurrence at colonoscopy (n = 2), or suspected extrapelvic recurrence in follow-up (n = 5).

Locoregional recurrence and distant metastases

Final diagnosis was confirmed by histopathological evidence in 12 patients (57.1%) and by clinical follow-up in nine patients (42.9%). Eight patients (38.1%) had extrapelvic metastases with no evidence of pelvic recurrence. Seven patients (33.3%) had both pelvic recurrence and extrapelvic metastases, and two patients (9.5%) had pelvic recurrence only. ¹⁸F-FDG PET/CT was negative in two patients and positive in 19 patients. ¹⁸F-FDG PET/CT was true positive in 17 (80.9%) patients (Figures 1 and 2) and false positive in two (9.5%). Overall, the accuracy of ¹⁸F-FDG PET/CT was 90.5%, the negative predictive value was 100%, and the positive predictive value was 89.5%. The two false positive PET/CT findings were inflammation of retroperitoneal abscess and scar tissue in one patient, respectively (Figure 3). 90% of recurrence after curative resection occurs within the first 2 years. Fewer than 9% of recurrences occur after 2 years. Recurrent disease is frequently both pelvic recurrence and extrapelvic metastases (Table 1).

Figure 1 Perirectal recurrence. Endoscopic examination, transverse images and PET/CT images obtained 25 mo after surgery in a 39-year-old man. A: Colonoscopy at the level of tumor resection showed no evidence of recurrence; B: CT demonstrated perirectal soft tissue that might represent a local recurrent tumor or postoperative scar tissue (arrows); C, D: PET/CT revealed a perirectal lesion with high FDG uptake (arrows); E: Local recurrence was confirmed by PET/CT guided tissue core biopsy (arrow); F: Whole body PET/CT confirmed local recurrent tumor (arrow) and no distant metastasis.

Figure 2 Extrapelvic metastases and perirectal recurrence. Plain abdominal radiograph, ES and PET/CT images obtained 30 mo after rectal cancer resection in a 41-year-old man. A, B: Plain abdominal radiograph and colonoscopy revealed the obstruction at the anastomotic site (arrows); C-F: PET/CT showed perirectal recurrence, peritoneal carcinomatosis and liver metastases (arrows).

Figure 3 False-positive results. PET/CT obtained in a 34-year-old woman 16 mo after rectal cancer resection. A-C: ¹⁸F-FDG uptake in the left side of the pelvis was misinterpreted as tumor recurrence (arrows); D, E: ¹⁸F-FDG uptake in the left side of the pelvis was unchanged after 6 mo PET/CT scan (arrows); F: MRI showed no changes of lesion 11 mo follow-up after first PET/CT examination (arrow). The final diagnosis of scar tissue was established by clinical and imaging follow-up.

Table 1 Frequency of locoregional recurrence and distant metastases.

Group	Location of recurrences	Frequency n
Pelvic recurrence group	Pelvic side walls nodes metastases	1
	Perirectal recurrence	1
Pelvic recurrence and extrapelvic metastases group	Perirectal recurrence	6
	Pelvic side walls nodes metastases	3
	Retroperitoneal lymph nodes metastases	4
	Abdominal wall metastasis	1
	Inguinal lymph nodes metastases	2
	Neck lymph nodes metastases	2
	Liver metastases	2
	Spleen metastases	1
	Lung metastases	4
	Canalis spinalis metastasis	1
	Bone metastases	2
	Peritoneal carcinomatosis	1
Extrapelvic metastases without pelvic recurrence group	Retroperitoneal lymph nodes	2
	Neck lymph nodes metastases	1
	Left axillary nodes	1
	Liver metastases	2
	Lung metastases	4
	Bone metastases	3
	Peritoneal carcinomatosis	1
	Abdominal wall metastasis	1

Salvage treatment guided by ¹⁸F-FDG PET/CT image

Surgical resection of pulmonary metastases was performed for potentially curative treatment in three patients who had previously undergone resection for rectal carcinoma with a single and peripheral new lung lesion identified by whole body ¹⁸F-FDG PET/CT. A one-year follow-up period of the three patients revealed that two of the patients were in good condition and new lung lesion had appeared in one patient five months after the resection of lung metastases. ¹⁸F-FDG PET/CT image also was also used to monitor salvage chemotherapy in four patients after two cycles of treatment and revealed the early response to the treatment in these patients (Figure 4).

Figure 4 Monitoring responses to pelvic recurrence and liver metastases. Three PET/CT scans were obtained in a 55-year-old woman five months after rectal cancer resection. A: PET/CT demonstrated a locoregional recurrence and liver metastasis foci (arrows) before salvage treatment; B: PET/CT showed obvious decreasing of intense activity after two cycles of chemotherapy (arrows); C: After six cycles of chemotherapy, PETCT imaging follow-up revealed good control of pelvic recurrence and liver metastases (arrows).

CT guided tissue core biopsy modulated with ¹⁸F-FDG PET/CT image

Five patients who suffered from perirectal recurrence and endoscopic examination of whom failed to get samples for histopathological diagnosis, underwent CT guided tissue core biopsy modulated with ¹⁸F-FDG PET/CT imaging (Figure 1). ¹⁸F-FDG PET/CT scan and biopsy procedure were completed in each patient with the same PET/CT system on a single day. These patients avoided exploratory laparotomy to obtain samples for histopathological evidence of recurrence.

DISCUSSION

The frequency of local recurrence after resection of rectal carcinoma is not negligible. Locoregional recurrence after resection of rectal carcinoma is a difficult clinical problem that adversely affects both survival and quality of life[11]. Following potentially curative standard/conventional surgical resection for adenocarcinoma of the rectum, the incidence of locoregional or distant treatment failure is related to the extent of transmural disease and the associated involvement of regional lymph nodes in metastases[12-14]. The incidence of locoregional failure is 8% to 21% in American Joint Committee on Cancer (AJCC) stage I disease, 29% to 44% in AJCC stage II disease, and 50% to 61% in AJCC stage III disease. The incidence of distant failure (as a component of failure) is up to 28% in AJCC stage I disease, 47% in AJCC stage II disease, and up to 74% in AJCC stage III disease[15-17]. However, surgical salvage of locoregional recurrence and distant metastases can be performed safely and can result in substantial long-term survival benefits for selected patients[18,19].

The current treatment strategy for rectal cancer aims detecting locoregional recurrence early by conventional medical modalities. Endoscopic examination is not always useful in such cases, because local recurrence of rectal cancer is often perirectal[20]. In our study, 10 patients had accepted endoscopic examinations one month before ¹⁸F-FDG PET/CT scan, which only revealed two suspicious locoregional recurrences. Conventional CT and MRI are also not reliable for detecting local recurrence in some clinical situations, because benign postoperative scar tissue can produce a mass that mimics recurrence[21,22]. Conventional anatomical methods for tumor detection might not accurately distinguish benign and malignant processes based on size criteria alone, and interpretation might be difficult when prior surgery or radiation therapy results in distortion of the normal anatomy[23]. In the current study, 15 patients underwent locoregional CT or MRI scan one month before the ¹⁸F-FDG PET/CT scan, which only revealed seven patients with suspicious local recurrences or distant metastases.

The major advantages of ¹⁸F-FDG PET/CT are the ability to perform full body examinations, the potential to detect locoregion recurrence and distant metastases in one single examination, and the possibility of distinguishing new active disease from scar or necrotic tissue[24,25]. It has been reported that PET/CT using the radiolabeled glucose analog ¹⁸F-FDG was valuable in detecting locoregional recurrence of colorectal cancer, particularly when anatomic imaging modalities have presented equivocal interpretations[26]. According to our results, early detection of extrapelvic metastases is also very important. Our data demonstrated that only 9.5% (2/21) patients had pelvic recurrence, 38% (8/21) patients had extrapelvic metastases with no evidence of pelvic recurrence and 33.3% (7/21) patients had both pelvic recurrence and extrapelvic metastases. In contrast to the results of endoscopic examination and CT/MRI scans, whole body ¹⁸F-FDG PET/CT is useful for the early detection of locoregion recurrence and extrapelvic metastases of resected rectal carcinoma, which are the key factors influencing salvage treatment plans for the candidates.

Salvage treatment for the relapse of rectal cancer consisted of radiotherapy alone or combined with chemotherapy and/or surgical resection[27]. Note that ¹⁸F-FDG PET/CT could be the best criterion for choosing individual salvage treatment plans[28,29]. Resections are effective for some patients with hepatic or pulmonary metastases of colorectal cancer, but the best selection criteria for resections and the effective treatment for recurrence after the resections have not been determined[30]. However, identifying candidates for this aggressive surgical approach is controversial, because the tumor and host factors that allow systemic disease to be controlled with local therapy are unknown[31]. ¹⁸F-FDG PET/CT provides important additional information in patients with presumed resectable colorectal metastases to the liver, leading to a change of therapy in one fifth of patients[32,33].

In our study, surgical resection of pulmonary metastases was used in three patients who had previously undergone resection for rectal carcinoma with a single and peripheral new lung lesion identified by whole body PET/CT. A one-year follow-up period revealed that two of the patients were in a good condition but that a new lung lesion had appeared in the third patient five months after the resection of lung metastases. ¹⁸F-FDG PET/CT image was used to guide chemotherapy and radiotherapy in four patients who suffered pelvic recurrence and extrapelvic metastases. Our data, although in a limited series of patients with a relatively short follow-up, showed that the use of whole body PET/CT scan will be helpful for making salvage treatment plans.

Five patients suffered from perirectal recurrence and endoscopic examination failed to get samples for histopathological diagnosis. In such clinical conditions, minimally invasive image-guided biopsy might be the first choice. CT guided biopsy is the most common technique for pathological diagnosis[34]. CT guidance is favorable in small lesions, has reliable three-dimensional control of the biopsy needle path, and, with contrast enhancement, CT can allow discrimination of lesions and vital anatomic vascular and neural structures. However, CT may not accurately distinguish benign postoperative scar tissue and local recurrence based on anatomical characters alone[35]. We performed CT guided tissue core biopsy modulated with ¹⁸F-FDG PET/CT imaging in five patients, which might have improved the diagnostic ability of PET/CT, especially when a definite diagnosis was difficult to make. This diagnostic algorithm has the possibility to complete diagnosis and staging of malignant solid tumors in one day.

Our study had several limitations. The first was our small sample size, which might have limited the statistical significance of the results. Due to the retrospective nature of the study, we did not get all of the medical details for some of the patients. There are also some disadvantages associated with PET/CT imaging[36,37]. For example, small tumors might go undetected because partial-volume effects result in a falsely low measurement of true ¹⁸F-FDG activity. Another drawback of PET/CT is that ¹⁸F-FDG frequently accumulates in areas of inflammation. In our study, the two false positive PET/CT results were inflammation of retroperitoneal abscess and anastomotic granulation tissue, respectively. Physiological variants and benign pathological causes of ¹⁸F-FDG uptake can be specifically recognized and properly categorized in other instances.

It is possible that ¹⁸F-FDG PET/CT scanning can make a valuable contribution in the detection of locoregional recurrence and distant metastases after rectal cancer resection. The use of ¹⁸F-FDG PET/CT might assist the clinician in several ways: such as by guiding surgical resection of hepatic or pulmonary metastases; by improving treatment plans for salvage chemotherapy and radiotherapy; by monitoring the early response to salvage treatment; and by guiding biopsies of suspicious lesions on CT and endoscopic examinations. Our results support the routine use of ¹⁸F-FDG PET/CT to evaluate suspicious locoregional recurrence and distant metastases in the restaging of rectal cancer after curative resection.

COMMENTS

Background

The paper tries to evaluate the value of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in the restaging of resected rectal cancer. They report an accuracy of ¹⁸F-FDG PET/CT of 90.5%, a negative predictive value of 100% and a positive predictive value of 89.5%, when used in patients with rectal cancer to evaluate locoregional recurrence. They conclude that ¹⁸F-FDG PET/CT is useful as a routine technique to evaluate suspicious locoregional recurrence and distant metastases in the restaging of rectal cancer after curative resection. The study was well designed and performed and appropriate methods were used, however, some changes would help to improve the manuscript

Innovations and breakthroughs

The authors use ¹⁸F-FDG PET/CT in 21 patients. They carried out one scan for all patients and up to four scans for one patient who had undergone curative surgical resection for rectal carcinoma to determine suspicious relapse. They demonstrated the usefulness of this technique to evaluate recurrences and/or distant metastases. Also, they confirmed the results with histological analysis or clinical and imaging follow-up.

Applications

This is a powerful technology for tumor visualization, staging and recurrence diagnosis.

Peer review

This is an interesting article on the application of PET-CT to the study of the relapse after rectal cancer resection. The conclusions are sound and might be of interest for the clinical community.