Mediastinal lymph node staging in suspected lung cancer: comparison of positron emission tomography with F-18-fluorodeoxyglucose and mediastinoscopy

BACKGROUND: In patients with bronchogenic carcinoma, mediastinal lymph node staging is essential for determining treatment options. In this retrospective analysis we compared the results of positron emission tomography (PET) using F-18 fluorodeoxyglucose with those of mediastinoscopy in nodal staging for suspected bronchogenic carcinoma. METHODS: From March 1997 to June 2001, 102 patients (86 male,16 female, age 62 +/- 9 years) underwent both PET and mediastinoscopy for radiologically suspected mediastinal lymph node disease in bronchogenic carcinoma. Total body emission scans were acquired 90 to 150 minutes after injection of 230 MBq of F-18 fluorodeoxyglucose. Mediastinoscopic evaluation of lymph node stations was performed according to the method of Mountain and Dresler (1R, 1L, 2L, 2R, 4L, 4R,7). Patients were eligible if surgical staging was performed within 6 weeks after the PET scan. RESULTS. Of the 102 patients, benign lesions were diagnosed in 15. In 87 patients malignant disease was proven by histology, and bronchogenic carcinoma was found in 82. Of 469 nodal stations analyzed, malignancy was documented by histology in 84. In PET analysis 79 true-positive and 304 true-negative samples were found. Five lymph node stations were false negative, and 81 samples were false positive. False-positive findings in PET frequently were seen in inflammatory lung disease. The sensitivity of PET was 94.1%, specificity was 79% with a diagnostic accuracy of 81.6%. The positive predictive value of PET was 49.3%, and the negative predictive value was 98.4%. CONCLUSIONS: In patients with positive PET scan results histologic verification appears necessary for exact lymph node staging. In view of the negative predictive value mediastinoscopy can be omitted in patients with bronchogenic carcinoma whose PET scan results were negative.     

Factors associated with false-positive staging of lung cancer by positron emission tomography

BACKGROUND: Positron emission tomography imaging is gaining popularity as a noninvasive staging tool in non-small cell lung cancer. Nonmalignant processes can also affect radio-tracer uptake. This study seeks to identify factors associated with false-positive staging of mediastinal metastases. METHODS: A retrospective review was performed of 100 patients with early stage non-small cell lung cancer referred for positron emission tomography scan evaluation. All had pathologic confirmation of their disease. Positron emission tomography scans, radiology records, operative reports, and pathology results were reviewed. Patients with positron emission tomography scans interpreted as positive for mediastinal involvement and negative pathology at operation were selected. RESULTS: Seven patients were found to have a false-positive positron emission tomography evaluation for mediastinal metastases. All but 1 patient had a concurrent inflammatory process or an anatomic factor associated with the false positive. The sensitivity and specificity in detecting involved mediastinal nodes was 87.5% and 90.7%, respectively. The negative predictive value was 95.8%. CONCLUSIONS: Although positron emission tomography has been established as an accurate modality to stage non-small cell lung cancer, false-positive evaluation of mediastinal metastases can occur in the setting of concurrent inflammatory lung diseases or for centrally located tumors. Pathologic evaluation of mediastinal disease should be pursued whenever suggested by a positive positron emission tomography scan especially in the face of those factors described.     

Preoperative intrathoracic lymph node staging in patients with non-small-cell lung cancer: accuracy of integrated positron emission tomography and computed tomography

Objective: To evaluate the accuracy of integrated positron emission tomography with ¹⁸F-fluoro-2-deoxy-d-glucose (FDG) and computed tomography (PET/CT) in preoperative intrathoracic lymph node staging in patients with non-small-cell lung cancer (NSCLC) and to ascertain the role of invasive staging in verifying positron emission tomography (PET)/computed tomography (CT) results. Methods: Retrospective, single institution study of consecutive patients with suspected or pathologically proven, potentially resectable NSCLC undergoing integrated PET/CT scanning in the same PET centre. Lymph node staging was pathologically confirmed on tissue specimens obtained at mediastinoscopy and/or thoracotomy. Statistical evaluation of PET/CT results was performed on a per-patient and per-nodal-station bases. Results: A total of 1001 nodal stations (723 mediastinal, 148 hilar and 130 intrapulmonary) were evaluated in 159 patients. Nodes were positive for malignancy in 48 (30.2%) out of 159 patients (N1 = 17; N2 = 30; N3 = 1) and 71 (7.1%) out of 1001 nodal stations (N1 = 24; N2 = 46; N3 = 1). At univariate analysis, lymph node involvement was significantly associated (p < 0.05) with the following primary tumour characteristics: increasing diameter, maximum standardised uptake value >9, central location and presence of vascular invasion. PET/CT staged the disease correctly in 128 out of 159 patients (80.5%), overstaging occurred in nine patients (5.7%) and understaging in 22 patients (13.8%). The overall sensitivity, specificity, positive and negative predictive values, and accuracy of PET/CT for detecting metastatic lymph nodes were 54.2%, 91.9%, 74.3%, 82.3% and 80.5% on a per-patient basis, and 57.7%, 98.5%, 74.5%, 96.8% and 95.6% on per-nodal-station basis. With regard to N2/N3 disease, PET/CT accuracy was 84.9% and 95.3% on a per-patient basis and on per-nodal-station basis, respectively. Referring to nodal size, PET/CT sensitivity to detect malignant involvement was 32.4% (12/37) in nodes <10 mm, and 85.3% (29/34) in nodes ≥10 mm. Conclusion: Our data show that integrated PET/CT provides high specificity but low sensitivity and accuracy in intrathoracic nodal staging of NSCLC patients and underscore the continued need for surgical staging.     

Axillary staging using positron emission tomography in breast cancer patients qualifying for sentinel lymph node biopsy

Axillary lymph node dissection (ALND) is the standard of care for nodal staging of patients with invasive breast cancer. Due to significant somatic and psychological side effects, replacement of ALND with less invasive techniques is desirable. The goal of this study was to evaluate the clinical usefulness of axillary lymph node (ALN) staging by means of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in breast cancer patients qualifying for sentinel lymph node biopsy (SLNB). FDG-PET was performed within 1 week before surgery in 24 clinically node-negative breast cancer patients with tumors smaller than 3 cm. Sentinel lymph nodes (SLNs) were identified by preoperative lymphoscintigraphy following peritumoral technetium 99m-labeled colloid albumin injection, and by intraoperative gamma detector and blue dye localization. Following SLNB, a standard ALND was performed. Serial sectioning and immunohistochemistry of the SLN as well as standard histologic examination of the non-SLN was performed. FDG-PET detected all primary breast cancers. Staging of ALNs by PET was accurate in 15 of 24 patients (62.5%), whereas PET staging was false negative in 8 of 10 node-positive patients and false-positive in 1 patient. The sensitivity, specificity, positive predictive value, and negative predictive value of FDG-PET for nodal status was 20%, 93%, 67%, and 62%, respectively. The mean diameter of false-negative ALN metastases was 7.5 mm (range 1-15 mm). Lymph node staging using FDG-PET is not accurate enough in clinically node-negative patients with breast cancer qualifying for SLNB and should not be used for this purpose.     

The use of 18F-FDG positron emission tomography to detect mediastinal lymph nodes in metastatic breast cancer

BackgroundTo assess the predictive value of ¹⁸F-fluorodeoxyglucose positron-emission tomography (FDG–PET/CT) in detecting mediastinal lymph node metastasis with histopathologic verification in breast cancer (BC) patients.Materials and methodsBetween February 2012 and October 2019, 37 BC patients who underwent histopathological verification for FDG-PET positive mediastinal lymph nodes were retrospectively analyzed. Nine patients (24%) were screened before beginning treatment, while 27 (76%) were screened at the time of disease progression, an average of 39 months after completion of initial treatment.ResultsThe histopathologic diagnosis revealed lymph node metastasis from BC in 15 patients (40%) and benign disease in 22 patients (60%). The standardized uptake value (SUV_max) of mediastinal lymph nodes was significantly higher in patients with lymph node metastasis compared to those with benign histology (9.0 ± 3.5 vs. 5.9 ± 2.4; P = 0.007). The cut-off value of SUV_max after the ROC curve analysis for pathological lymph node metastasis was 6.4. Two of the 15 patients with mediastinal SUV_max ≤ 6.4 and 13 of the 22 patients with SUV_max > 6.4 had lymph node metastasis. Age and pathological findings were prognostic factors for overall survival in univariate analysis. The treatment decision was changed in 19 patients (51%) after mediastinoscopic evaluation of the entire cohort.ConclusionsThis is the first study to support the need for pathologic confirmation of a positive PET/CT result following evaluation of mediastinal lymph nodes for staging BC, either at initial diagnosis or at the time of progression. Treatment decisions were consequently altered for nearly half of the patients.     

A novel approach to positron emission tomography in lung cancer

18F-fluorodeoxyglucose positron emission tomography-computed tomography is integral to the staging of lung cancer. We describe the combined use of diagnostic preoperative 18F-fluorodeoxyglucose positron emission tomography-computed tomography, intraoperative 18F-fluorodeoxyglucose handheld gamma probe detection, and immediate postoperative 18F-fluorodeoxyglucose positron emission tomography-computed tomography patient and specimen imaging for improved staging and determination of adequacy of mediastinal lymph node dissection.     

Meta-analysis of positron emission tomographic and computed tomographic imaging in detecting mediastinal lymph node metastases in nonsmall cell lung cancer

A systematic review was undertaken to select studies that compared the accuracy of 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography with computed tomographic imaging in detecting mediastinal lymph node metastases in patients with nonsmall cell lung cancer. Two authors selected relevant articles according to predefined criteria. With a meta-analytic method, summary receiver operating characteristic curves were constructed. The point on the receiver operating characteristic curve with equal sensitivity and specificity for 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography was Q* = 0.90 (95% confidence interval [CI], 0.86 to 0.95). For computed tomography it was 0.70 (95% CI, 0.65 to 0.75). The difference was highly significant (p < 0.0001). We conclude that 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography is more accurate than computed tomography in detecting mediastinal lymph node metastases.     

The role of integrated positron emission tomography-computerized tomography in evaluating and staging patients with non-small cell lung cancer

The stage of non-small cell lung cancer (NSCLC) determines that the treatment strategy and proper staging lead to improved survival. Integrated positron emission tomography/computerized tomography (CT) scan provides more accurate staging and better targets for biopsy than traditional methods such as CT scans of the chest and upper abdomen, bone scans, and magnetic resonance imaging scans. Integrated positron emission tomography/CT is the best initial test for an indeterminate pulmonary nodule that is 8 mm or greater; for the noninvasive staging of patients with NSCLC, it is the only test that produces a quantitative assessment of an NSCLC's virulence or biologic aggressiveness in a particular patient and is the best tool for restaging patients after radiation and and/or chemotherapy. Finally, its use as a tool for postoperative surveillance is under study.     

Non-sentinel lymph node metastases in breast cancer patients with metastatic sentinel nodes

BACKGROUND: Sentinel lymph node biopsy (SLNB) has been shown to be relatively accurate in axillary nodal staging in breast cancer. In more than half of the patients with metastatic sentinel lymph node (SLN), the SLN was the only lymph node involved in the axilla. Methods: A retrospective analysis was performed for those female Chinese breast cancer patients who underwent SLNB. All patients had axillary dissection after SLNB. Those patients with metastatic SLN were selected for analysis. Various tumour factors and SLN factors were analysed to study the association with residual lymph node metastasis. Results: A total of 139 SLNB was performed. The success rate of SLN localization, false negative rate and accuracy were 92%, 9% and 95%, respectively. Fifty-five patients had metastases in the SLN. In 38 patients (69%), SLN was the only lymph node involved in the axilla. Tumours <3 cm, a single metastatic SLN, presence of micro metastases and the absence of extracapsular spread in the SLN were associated with the absence of metastasis in the non-sentinel lymph nodes. Conclusion: Sentinel lymph node biopsy is accurate in the nodal staging of Chinese breast cancer patients. Several factors such as tumour <3 cm, a single metastatic SLN, micro metastases and the absence of extracapsular spread in the sentinel node(s) are useful predictors for the absence of residual disease in the axilla. With further studies and verification, these factors may prove to be important in determining which patients with metastatic SLN will require further axillary treatment. Until such information is available, axillary dissection should be performed when positive sentinel nodes are found.     

The role of positron emission tomography in selecting patients with metastatic cancer for adrenalectomy

Metastases to the adrenal glands usually signal disseminated disease. However, isolated metastases do occur that may be curable with adrenalectomy. Functional imaging with positron emission tomography (PET) can differentiate benign from malignant pathology and isolated from disseminated metastases. The purpose of this study was to determine whether PET scanning can influence the outcome of adrenalectomy for metastatic disease. We conducted a retrospective review of eight patients undergoing adrenalectomy for presumed isolated metastatic disease from 1985 through 1997. The patients included six women and two men with an average age of 58 (range, 36-74). Their primary tumors were six lung carcinomas, one renal cell carcinoma, and one colon carcinoma. The adrenal masses were located on the right in six patients, on the left in one, and bilaterally in one. Before operation, all patients were evaluated by chest and abdominal CT. Four patients were also evaluated by PET scan. Six right, one left, and one bilateral adrenalectomies were performed. Associated organ resections included two right partial nephrectomies and one right total nephrectomy, one left partial nephrectomy, two distal pancreatectomies, one splenectomy, and two partial hepatic resections. All eight patients survived operation. There were no major perioperative complications, but one patient required readmission for congestive heart failure. Three of the four patients who did not have PET scanning died from 4 to 48 months after operation with disseminated disease from lung, colon, and renal carcinoma respectively. The remaining patient who did not have PET scanning is alive and well 11 years later. Two of the four patients who had PET scans showing isolated disease are alive at 28 and 43 months after operation, whereas the other two died of disseminated disease at 29 and 36 months after operation. We conclude that 1) adrenalectomy can provide survival benefit in patients with isolated metastases, and 2) PET scanning is useful in confirming isolated metastatic disease and selecting patients for adrenalectomy.     

Micrometastasis to lymph nodes in stage I left lung cancer patients

BACKGROUND: To evaluate the frequency and clinicopathological characteristics of lymph node micrometastasis in left lung cancer patients diagnosed to be stage IA and IB based on routine histopathologic examinations, we examined the lymph nodes in patients who had undergone an extended mediastinal lymphadenectomy, using immunohistochemical methods. METHODS: Paraffin-embedded tissue sections from the lymph nodes in 49 patients with stage I left lung cancers were studied. We used AE1/AE3 as the anticytokeratin and Ber-EP4 as the antiepithelial cell antibodies when performing immunohistochemical staining. RESULTS: We identified micrometastasis of the lymph nodes in 13 (26.5%) of 49 patients with stage I left lung cancer. NO disease was reclassified as N1 disease in 5 cases, N2 disease in 6 cases, and N3 disease in 2 cases. The location of the micrometastatic lymph nodes proved to be wide regions including the contralateral and highest mediastinal nodes, and 6 (46.2%) out of the 13 patients with micrometastasis were thus presumed not to be completely eliminated by a standard lymphadenectomy through an ipsilateral thoracotomy. The five year survival rate of patients with reclassified N1 to N3 disease was 74%, and the presence of micrometastasis was found to have no significant effect on the outcomes. CONCLUSIONS: The micrometastatic involvement of the lymph nodes was both more frequent and extensive than expected even in stage I left lung cancer. These results suggest that an extended mediastinal lymphadenectomy may therefore be required for the locoregional control of stage I left lung cancer patients.     

The prognostic value of lymph node staging with prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and extended pelvic lymph node dissection in node-positive patients with prostate cancer

Objectives

To investigate whether patients with suspected pelvic lymph node metastases (molecular imaging [mi] N1) on staging prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) had a different oncological outcome compared to those in whom the PSMA PET/CT did not reveal any pelvic lymph node metastases (miN0).

Patients and Methods

All patients with pelvic lymph node metastatic (pN1) disease after robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND) between January 2017 and December 2020 were included. To assess predictors of biochemical progression of disease after RARP, a multivariable Cox regression analysis was performed, including number of tumour-positive lymph nodes, diameter of the largest nodal metastasis, and extranodal extension.

Results

In total, 145 patients were diagnosed with pN1 disease after ePLND. The median biochemical progression-free survival in patients with miN0 on PSMA PET/CT was 13.7 months, compared to 7.9 months in patients with miN1 disease (P = 0.006). On multivariable Cox regression analysis, both number of tumour-positive lymph nodes (>2 vs 1–2: hazard ratio [HR] 1.97; P = 0.005) and diameter of the largest nodal metastasis (HR 1.12; P < 0.001) were significant independent predictors of biochemical progression of disease.

Conclusion

Patients in whom pelvic lymph node metastases were suspected on preoperative PSMA imaging (miN1), patients diagnosed with >2 tumour-positive lymph nodes, and patients with a larger diameter of the largest nodal metastasis had a significantly increased risk of biochemical disease progression after surgery.