Diagnostic efficacy of [11C]choline positron emission tomography/computed tomography compared with conventional computed tomography in lymph node staging of patients with bladder cancer prior to radical cystectomy

Background

Current imaging techniques are of limited value for lymph node (LN) staging in bladder cancer (BCa) patients scheduled for radical cystectomy (RC).

Objective

Evaluate the diagnostic efficacy of [11C]choline positron emission tomography in combination with computed tomography (PET/CT) for LN staging of patients with BCa scheduled for RC and compare that efficacy with the diagnostic efficacy of CT and the gold standard of histopathologic evaluation.

Design, setting, and participants

From June 2004 to May 2007, 44 patients with localized BCa were staged with [11C]choline PET with low-dose CT for attenuation correction and simultaneous intravenous and rectal contrast-enhanced diagnostic CT before RC and pelvic lymph node dissection (PLND). LNs were dissected from the internal and external iliac arteries up to the origin of the inferior mesentery artery according to a template with 14 predefined anatomic fields.

Intervention

Diagnostic [11C]choline PET/CT before RC and regional LN dissection.

Measurements

Histopathologic findings of resected LN were correlated with the results of [11C]choline PET/CT and CT alone in a patient- and field-based manner. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of [11C]choline PET/CT and CT were assessed.

Results and limitations

LN metastases were found in 12 of 44 patients (27%). On patient-based analysis, sensitivity, specificity, PPV, NPV, and accuracy for [11C]choline PET/CT were calculated as 58%, 66%, 39%, 81%, and 64%, respectively; and for CT the calculated percentages were 75%, 56%, 39%, 86%, and 61%, respectively. Twenty-five of 471 dissected LN fields (5%) showed metastases. On field-based analysis, sensitivity, specificity, PPV, NPV, and accuracy for [11C]choline PET/CT were 28%, 95%, 21%, 96%, and 91%, respectively; for CT, the calculated percentages were 39%, 92%, 20%, 96%, and 90%, respectively. Limitations of this study are small patient number and the fact that not all patients underwent extensive PLND.

Conclusions

In patients with BCa who were scheduled for RC, preoperative LN staging with [11C]choline PET/CT was not able to improve diagnostic efficacy compared with conventional CT alone.     

Scanning with 18F-FDG-PET/CT for Detection of Pelvic Nodal Involvement in Inguinal Node-Positive Penile Carcinoma

Background

Penile carcinoma patients with inguinal lymph node involvement (LNI) have an increased risk for pelvic nodal involvement with or without distant metastases.

Objective

To evaluate the diagnostic accuracy of fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) with computed tomography (CT; 18F-FDG PET/CT) scanning in determining further metastatic spread in patients with tumour-positive inguinal nodes.

Design, setting, and participants

Eighteen patients with penile squamous cell carcinoma with unilateral or bilateral cytologically tumour-positive inguinal disease underwent whole-body 18F-FDG-PET/CT scanning for tumour staging.

Measurements

Images were blindly assessed by two nuclear medicine physicians. All scans were evaluated for pelvic nodal involvement per basin and for distant metastases. Histopathology (when available), radiologic imaging, and clinical follow-up (with a minimum of 1 yr) served as a reference standard. The diagnostic value of PET/CT scanning for predicting pelvic nodal involvement was evaluated using standard statistical methods.

Results and limitations

The reference was available in 28 of the 36 pelvic basins. Of the 11 tumour-positive pelvic basins, 10 were correctly predicted by PET/CT scan, as were all 17 tumour-negative pelvic basins. PET/CT scan showed a sensitivity of 91%, a specificity of 100%, a diagnostic accuracy of 96%, a positive predictive value of 100%, and a negative predictive value of 94% in detecting pelvic nodal involvement. Additionally, PET/CT scans showed distant metastases in five patients. In four patients, the presence of distant metastases could be confirmed, while in one patient, no radiologic confirmation was found for that particular lesion. A potential limitation is that the diagnostic accuracy of PET/CT scanning was calculated on 28 pelvic basins only. Furthermore, no comparison was made with conventional CT scans, as not all patients had undergone contrast-enhanced CT scans.

Conclusions

PET/CT scanning appears promising for detecting pelvic lymph node metastases with great accuracy, and it identifies distant metastases in penile carcinoma patients with inguinal LNI. In our practice, PET/CT scanning has become part of routine staging in such patients.     

Utility of Choline Positron Emission Tomography/Computed Tomography for Lymph Node Involvement Identification in Intermediate- to High-risk Prostate Cancer: A Systematic Literature Review and Meta-analysis

Context

Determination of tumour involvement of regional lymph nodes in patients with prostate cancer (PCa) is of key importance for the proper planning of treatment.

Objectives

To provide a critical overview of published reports and to perform a meta-analysis about the diagnostic performance of 18F-choline and 11C-choline positron emission tomography (PET) or PET/computed tomography (CT) in the lymph node staging of PCa.

Evidence acquisition

A Medline, Web of Knowledge, and Google Scholar search was carried out to select English-language articles published before January 2012 that discussed the diagnostic performance of choline PET to individualise lymph node disease at initial staging in PCa patients. Articles were included only if absolute numbers of true-positive, true-negative, false-positive, and false-negative test results were available or derivable from the text and focused on lymph node metastases. Reviews, clinical reports, and editorial articles were excluded. All complete studies were reviewed; thus qualitative and quantitative analyses were performed.

Evidence synthesis

From the year 2000 to January 2012, we found 18 complete articles that critically evaluated the role of choline PET and PCa at initial staging. The meta-analysis was carried out and consisted of 10 selected studies with a total of 441 patients. The meta-analysis provided the following results: pooled sensitivity 49.2% (95% confidence interval [CI], 39.9–58.4) and pooled specificity 95% (95% CI, 92–97.1). The area under the curve was 0.9446 (p < 0.05). The heterogeneity ranged between 22.7% and 78.4%. The diagnostic odds ratio was 18.999 (95% CI, 7.109–50.773).

Conclusions

Choline PET and PET/CT provide low sensitivity in the detection of lymph node metastases prior to surgery in PCa patients. A high specificity has been reported from the overall studies. Studies carried out on a larger scale with a homogeneous patient population together with the evaluation of cost effectiveness are warranted.     

Die Positronenemissionstomographie zur präoperativen Lymphknotendiagnostik bei Ösophaguskarzinom

Background

Exact preoperative staging is a prerequisite for the indication and the choice of appropriate operative technique for patients with esophageal carcinoma. The objective of this prospective study was to assess whether positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) increases the accuracy of preoperative lymph node staging with standard computed tomography (CT) and thus leads to a different surgical approach.

Patients and methods

Fifty-eight patients with carcinoma of the esophagus (46 men and 12 women) with a median age of 61 years underwent FDG-PET imaging of the neck, chest, and abdomen as well as CT of the chest and abdomen. Sensitivity, specificity, and accuracy were calculated for both imaging techniques to evaluate the detection of histologically verified lymph node metastases.

Results

The FDG-PET showed higher specificity, whereas CT proved to be more accurate for detecting lymph node metastases not only of the abdomen (73% vs 59%) but also of the thorax (73% vs 63%). Resections were transhiatal in 23 patients and transthoracal in 16. As a supplement to conventional CT diagnostic procedure, FDG-PET was not decisive for the surgical approach.

Conclusions

Altogether, pretherapeutical PET imaging did not increase the accuracy of lymph node staging for our patients with esophageal carcinoma, which had already been defined through CT. Therefore, no new consequences resulted for the surgical procedure. Due to the high costs involved with PET investigation, lymph node staging with it is momentarily indicated mainly for clinical studies and when CT does not offer unequivocal results. Increased sensitivity of the already advantageous whole-body FDG-PET imaging by means of tumor-affinitive radiopharmaceuticals and optimized apparatus resolution could lead to new indications for this staging procedure.     

18F-Fluoroethylcholine PET/CT Identifies Lymph Node Metastasis in Patients with Prostate-Specific Antigen Failure After Radical Prostatectomy but Underestimates Its Extent

Background

The detection of lymph node metastases (LNMs) is one of the biggest challenges in imaging in urology.

Objective

To evaluate the accuracy of combined 18F–fluoroethylcholine (FEC) positron emission tomography (PET)/computed tomography (CT) in the detection of LNMs in prostate cancer (PCa) patients with rising prostate-specific antigen (PSA) level after radical prostatectomy.

Design, settings, and participants

From June 2005 until November 2011, 56 PCa patients with biochemical recurrence after radical prostatectomy underwent bilateral pelvic and/or retroperitoneal lymphadenectomy based on a positive 18F-FEC PET/CT scan.

Outcome measurements and statistical analysis

The findings of PET/CT were compared with the histologic results.

Results and limitations

Median PSA value at the time of 18F-FEC PET/CT analysis was 6.0 ng/ml (interquartile range: 1.7–9.4 ng/ml). In 48 of 56 (85.7%) patients with positive 18F-FEC PET/CT findings, histologic examination confirmed the presence of PCa LNMs. Of 1149 lymph nodes that were removed and histologically evaluated, 282 (24.5%) harbored metastasis. The mean number of lymph nodes removed per surgical procedure was 21 (standard deviation: ±18.3). A lesion-based analysis yielded 18F-FEC PET/CT sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 39.7%, 95.8%, 75.7%, and 83.0%, respectively.A site-based analysis yielded sensitivity, specificity, PPV, and NPV of 68.4%, 73.3%, 81.3%, and 57.9%, respectively. Patients with negative PET/CT did not undergo surgery, thus sensitivity, specificity, and negative predictive value on a patient basis could not be calculated.

Conclusions

A positive 18F-FEC PET/CT result correctly predicted the presence of LNM in the majority of PCa patients with biochemical failure after radical prostatectomy but did not allow for localization of all metastatic lymph nodes and therefore was not adequately accurate for the precise estimation of extent of nodal recurrence in these patients.     

Major Reduction in Axillary Lymph Node Dissections After Neoadjuvant Systemic Therapy for Node-Positive Breast Cancer by combining PET/CT and the MARI Procedure

Background

Axillary lymph node dissection (ALND) is frequently performed for node-positive (cN+) breast cancer patients. Combining positron emission tomography/computed tomography (PET/CT) before-NST and the MARI (marking axillary lymph nodes with radioactive iodine seeds) procedure after neoadjuvant systemic therapy (NST) has the potential for avoiding unnecessary ALNDs. This report presents the results from implementation of this strategy.

Methods

All breast cancer patients treated with NST at the Netherlands Cancer Institute who underwent a PET/CT and the MARI procedure from July 2014 to July 2017 were included in the study. All the patients underwent tailored axillary treatment according to a protocol based on the combined results of PET/CT before NST and the MARI procedure after NST. With this protocol, patients showing one to three FDG-avid axillary lymph nodes (ALNs) on PET/CT (cN<4) and a tumor-negative MARI node receive no further axillary treatment. All cN (<4) patients with a tumor-positive MARI node receive locoregional radiotherapy, as well as patients with four or more FDG-avid ALNs [cN(4+)] and a tumor-negative MARI node after NST. An ALND is performed only for cN(4+) patients with a tumor-positive MARI node.

Results

The data of 159 patients who received a PET/CT before NST and a MARI procedure after NST were analyzed. Of these patients, 110 had one to three FDG-avid ALNs and 49 patients showed four or more FDG-avid ALNs on PET/CT before NST. For 130 patients (82%), ALND was omitted. Locoregional radiotherapy was administered to 91 patients (57%), and 39 patients (25%) received no further axillary treatment.

Conclusion

Combining pre-NST axillary staging with PET/CT and post-NST staging with the MARI procedure resulted in an 82% reduction of ALNDs for cN?+?breast cancer patients.

     

Lymph node-positive bladder cancer treated with radical cystectomy and lymphadenectomy: effect of the level of node positivity

Background

The extent of lymphadenectomy needed to optimize oncologic outcomes after radical cystectomy (RC) for patients with regionally advanced bladder cancer (BCa) is unclear.

Objective

Evaluate the effect of the location of lymph node metastasis on recurrence-free survival (RFS) and cancer-specific survival (CSS) for patients undergoing RC with a mapping pelvic lymph node dissection (PLND).

Design, setting, and participants

A study of 591 patients undergoing RC with mapping PLND was completed between 2000 and 2010. Median follow-up was 30 mo.

Intervention

RC with mapping PLND.

Measurements

We evaluated the impact of lymph node involvement by location on disease outcomes using the 2010 TNM staging system. Survival estimates were described using Kaplan-Meier methods. Gender, age, pathologic stage, histology, number of positive nodes, location of positive nodes, node density, use of perioperative chemotherapy, and grade were evaluated as predictors of RFS and CSS using multivariate Cox proportional hazard regression.

Results and limitations

Overall, 114 patients (19%) had lymph node involvement, and 42 patients (7%) had pN3 disease. On multivariate analysis, the number of positive lymph nodes (one or two or more) was significantly associated with increased risk of cancer-specific death (hazard ratio [HR]: 1.9 [95% confidence interval (CI), 1.04–3.46], p = 0.036; versus HR: 4.3 [95% CI, 2.25–8.34], p < 0.0005). Positive lymph node location was not an independent predictor of RFS or CSS. Five-year RFS for pN3 patients undergoing RC with PLND was 25% (95% CI, 10–42). This finding was not statistically different from our pN1 and pN2 patients (38% [95% CI, 22–54] and 35% [95% CI, 11–60], respectively). This study is limited by the lack of prospective randomization and a control group.

Conclusions

The outcome for patients with involved common iliac lymph nodes was similar to the outcome for patients with primary nodal basin disease. These data support inclusion of the common iliac lymph nodes (pN3) in the nodal staging system for BCa. Lymph node location was not an independent predictor of outcome, whereas the number of positive lymph nodes was an independent predictor of worse oncologic outcome (pN1, pN2). Further refinements of the TNM system to provide improved prognostication are warranted.     

Pathologic Nodal Staging Score for Bladder Cancer: A Decision Tool for Adjuvant Therapy After Radical Cystectomy

Background

Radical cystectomy (RC) with pelvic lymph node dissection (PLND) is the standard of care for high-risk non–muscle-invasive and muscle-invasive bladder cancer (BCa).

Objective

To develop a model that allows quantification of the likelihood that a pathologically node-negative patient has, indeed, no positive nodes.

Design, setting, and participants

We analyzed data from 4335 patients treated with RC and PLND without neoadjuvant chemotherapy at 12 international academic centers.

Interventions

Patients underwent RC and PLND.

Outcome measurements and statistical analysis

We estimated the sensitivity of pathologic nodal staging using a beta-binomial model and developed a pathologic (postoperative) nodal staging score (pNSS) that represents the probability that a patient is correctly staged as node negative as a function of the number of examined nodes.

Results and limitations

Overall, the probability of missing a positive node decreases with the increasing number of nodes examined (52% if 3 nodes are examined, 40% if 5 are examined, and 26% if 10 are examined). The proportion of having a positive node increased proportionally with advancing pathologic T stage and lymphovascular invasion (LVI). Patients with LVI who had 25 examined nodes would have a pNSS of 80% (pT1), 88% (pT2), and 66% (pT3–T4), whereas 10 examined nodes were sufficient for pNSS exceeding 90% in patients without LVI and pT0–T2 tumors. This study is limited because of its retrospective design and multicenter nature.

Conclusions

We developed a tool that estimates the likelihood of lymph node (LN) metastasis in BCa patients treated with RC by evaluating the number of examined nodes, the pathologic T stage, and LVI. The pNSS indicates the adequacy of nodal staging in LN-negative patients. This tool could help to refine clinical decision making regarding adjuvant chemotherapy, follow-up scheduling, and inclusion in clinical trials.     

The diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography and computed tomography in staging bladder cancer: a single-institution study and a systematic review with meta-analysis

Purpose

The purpose of this study was to assess the diagnostic accuracy of 18F-fluorodeoxyglucose with positron emission tomography and computed tomography (FDG–PET–CT) to predict nodal metastases in patients with bladder cancer (BC) scheduled to undergo radical cystectomy (RC).

Methods

We retrospectively reviewed records of patients diagnosed with BC and scheduled to undergo RC at our center from January 2011 through February 2015, who also underwent FDG–PET–CT at the time of diagnosis. All patients underwent RC and an extended pelvic lymph node dissection as the reference standard. The primary endpoints were the sensitivity, specificity and overall accuracy of FDG–PET–CT in detecting lymph node metastasis. We also examined its accuracy in identifying distant metastasis. In addition, we conducted a protocol-driven systematic review and meta-analysis of accuracy of FDG–PET–CT for preoperative staging of BC, as compared to CT alone, as reported in individual studies. To assess the methodological quality of eligible studies, we used the QUADAS-2 tool (a revised tool for the Quality Assessment of Diagnostic Accuracy Studies) and pooled diagnostic accuracy measures using Meta-DiSc statistical software.

Results

For detecting nodal metastases in 78 patients, the sensitivity of FDG–PET–CT was 0.56 (95 % CI 0.29–0.80) and the specificity, 0.98 (95 % CI 0.91–1.00). Pooled sensitivity and specificity for detecting lymph node metastasis were 0.57 and 0.95, respectively. Positive likelihood ratio was 9.02. All lesions that were suspicious for distant metastasis were found to be positive on biopsy.

Conclusion

FDG–PET–CT was more accurate than CT alone in staging BC in patients undergoing surgery. Standardization of FDG–PET–CT protocol and cost-effectiveness analysis are required before widespread implementation of this technology.

     

Sentinel Lymph Node Biopsy in pediatric soft tissue sarcoma patients: Utility and concordance with imaging

Background

The purpose of this study was to report our experience with sentinel lymph node biopsy (SLNB) for pediatric soft tissue sarcomas to add to the limited literature about its feasibility, utility, and concordance with pre-operative imaging, including CT and ¹⁸ F-FDG PET (PET) scanning.

Methods

Medical records of patients with a sarcoma who underwent SLNB as part of their treatment for a soft tissue sarcoma at our institution from 2000 to 2011 were identified and reviewed.

Results

Eight patients underwent SLNB for soft tissue sarcoma during the study period. Two patients had positive SLNBs; both of these patients had rhabdomyosarcoma. Three patients with pathologically enlarged lymph nodes on CT scan underwent PET functional imaging prior to SLNB. The PET suggested the presence of nodal disease in all three patients; however, only one of these patients had a positive SLNB.

Conclusions

Our series confirms that SLNB is feasible in pediatric sarcoma patients. Small numbers preclude definitive conclusions regarding the utility of SLNB compared with PET, however our data suggest functional imaging alone may not be sufficient to definitively determine lymph node status in these patients. Surgical lymph node sampling may still need to be performed to accurately identify nodal status in pediatric patients with soft tissue sarcoma.     

Performance characteristics of computed tomography in detecting lymph node metastases in contemporary patients with prostate cancer treated with extended pelvic lymph node dissection

Background

Computed tomography (CT) is a commonly used noninvasive procedure for prostate cancer (PCa) staging. All previous studies addressing the ability of CT scan to predict lymph node invasion (LNI) were based on historical patients treated with limited pelvic lymph node dissection (PLND).

Objective

Assess the value of CT in predicting LNI in contemporary PCa patients treated with extended PLND (ePLND).

Design, setting, and participants

We evaluated 1541 patients undergoing radical prostatectomy and ePLND between 2003 and 2010 at a single center. All patients were preoperatively staged using abdominopelvic CT scan. All lymph nodes with a short axis diameter ≥10 mm were considered suspicious for metastatic involvement.

Intervention

All patients underwent preoperative CT scan, radical retropubic prostatectomy, and ePLND, regardless of PCa features at diagnosis.

Measurements

The performance characteristics of CT scan were tested in the overall patient population, as well as according to the National Comprehensive Cancer Network (NCCN) classification and according to the risk of LNI derived from a nomogram developed on an ePLND series. Logistic regression models tested the relationship between CT scan findings and LNI. Discrimination accuracy was quantified with the area under the curve.

Results and limitations

Overall, a CT scan that suggested LNI was found in 73 patients (4.7%). Of them, only 24 patients (32.8%) had histologically proven LNI at ePLND. Overall, sensitivity, specificity, and accuracy of CT scan were 13%, 96.0%, and 54.6%, respectively. In patients with low-, intermediate-, or high-risk PCa according to NCCN classification, sensitivity was 8.3%, 96.3%, and 52.3%, respectively; specificity was 3.6%, 97.3%, and 50.5%, respectively; and accuracy was 17.9%, 94.3%, and 56.1%, respectively. Similarly, in patients with a nomogram-derived LNI risk ≥50%, sensitivity, specificity, and accuracy were only 23.9%, 94.7%, and 59.3%, respectively. At multivariable analyses, inclusion of CT scan findings did not improve the accuracy of LNI prediction (81.4% compared with 81.3%; p = 0.8). Lack of a central scan review represents the main limitation of our study.

Conclusions

In contemporary patients with PCa, the accuracy of CT scan as a preoperative nodal-staging procedure is poor, even in patients with high LNI risk. Therefore, the need for and the extent of PLND should not be based on the results obtained by CT scan.     

<Superscript>99m</Superscript>Tc-HDP bone scintigraphy and <Superscript>18</Superscript>F-sodiumfluoride PET/CT in primary staging of patients with prostate cancer

Introduction/Aim

Correct staging of patients with prostate cancer is important for treatment planning and prognosis. Although bone scintigraphy with ^99mTc-phosphonates (BS) is generally advised for staging by guidelines in high risk prostate cancer, this imaging technique is hampered by a high rate of inconclusive results and moderate accuracy. Potentially better imaging techniques for detection of bone metastases such as ¹⁸F-sodiumfluoride PET/CT (NaF PET/CT) are therefore being evaluated. In this observational cohort study we evaluate the performance and clinical impact of both BS and NaF PET/CT in primary staging of patients with prostate cancer.

Methods

The first of two cohorts consisted of patients who received a BS while the second included patients who received a NaF PET/CT for primary staging of prostate cancer. For both cohorts the number of positive, negative and equivocal findings, calculated diagnostic performance of the imaging modality in terms of sensitivity and specificity, as well as the impact on clinical management were studied. The ranges of the diagnostic performance were calculated both assuming that equivocal findings were positive and assuming that they were negative for bone metastases. For the NaF PET/CT cohort the number of patients with signs of lymph node metastases on low dose CT were also recorded, including the impact of these findings on clinical management.

Results

One-hundred-and-four patients underwent NaF PET/CT, whereas 122 patients underwent BS. Sensitivities of 97–100 and 84–95% and specificities of 98–100 and 72–100% were found on a patient basis for detection of bone metastases with NaF PET/CT and BS, respectively. Equivocal findings warranted further diagnostic procedures in 2% of the patients in the NaF cohort and in 16% in the BS cohort. In addition NaF PET/CT demonstrated lymph node metastases in 50% of the included patients, of which 25% showed evidence of lymph node metastases only.

Conclusion

Our data indicate better diagnostic performance of NaF PET/CT compared to BS for detection of bone metastases in primary staging of prostate cancer patients. Less equivocal findings are encountered with NaF PET/CT. Moreover, NaF PET/CT has additional value over BS since lymph node metastases are encountered frequently.

     

Routine restaging PET/CT and detection of initial recurrence in sentinel lymph node positive stage III melanoma

Background

Follow-up of patients with sentinel lymph node–positive stage III melanoma uses history, physical exam, and cross-sectional imaging. The aim of this study was to evaluate positron emission tomographic (PET)/computed tomographic (CT) scans in the detection of recurrence.

Methods

From 2003 to 2009, a single-institution prospective database of all cutaneous melanoma patients was used to identify sentinel lymph node–positive stage III patients with disease-free survival >1 year and 1 restaging PET/CT scan.

Results

Thirty-eight patients were identified, with a median follow-up period of 27.5 months. Seven (18%) developed recurrence (median time to recurrence, 25 months). Recurrences were detected as follows: 3 by patients, 1 by physician, 1 by PET/CT scan and lactate dehydrogenase, 1 by PET/CT scan, and 1 by brain magnetic resonance imaging. One hundred eight follow-up PET/CT scans were performed. Two of 38 patients had asymptomatic metastases detected by routine restaging PET/CT scan, and there were 9 scans with false-positive results.

Conclusions

With short follow-up, the utility of routine PET/CT scans in identifying unsuspected recurrence in patients with sentinel lymph node–positive stage III melanoma appears minimal.     

The Impact of Lymphadenectomy and Lymph Node Metastasis on the Outcomes of Radical Cystectomy for Bladder Cancer

Context

The presence of lymph node metastases and the extent of lymphadenectomy have both been shown to influence the outcome of patients with muscle-invasive bladder cancer.

Objective

Current standards for detection of lymph node metastases, lymph-node mapping studies, histopathologic techniques, and risk factors in relation to lymph node involvement are discussed. The impact of lymph node metastases and the extent of lymphadenectomy on the outcome of patients treated with radical cystectomy are analyzed.

Evidence acquisition

A systematic literature review of bladder cancer and lymph nodes was performed searching the electronic databases Pubmed/Medline, Cochrane, and Embase. Articles were selected based on title, abstract, study format, and content by a consensus of all participating authors.

Evidence synthesis

Lymph node status is highly consequential in bladder cancer patients because the presence of lymph node metastases is predictive of poor outcome. Knowledge of primary landing sites of lymph node metastases is important for optimum therapeutic management. Accurate pathologic work-ups of resected lymph node tissue are mandatory. Molecular markers could potentially guide therapeutic decisions in the future because they may enable the detection of micrometastatic disease. In current series, radical cystectomy with an extended lymphadenectomy seems to provide a clinically meaningful therapeutic benefit compared with a limited approach. However, the anatomic boundaries of lymph node dissection are still under debate. Therefore, large prospective multicenter trials are needed to validate the influence of extended lymph node dissection on disease-specific survival.

Conclusions

An extended pelvic lymph node dissection (encompassing the external iliac vessels, the obturator fossa, the lateral and medial aspects of the internal iliac vessels, and at least the distal half of the common iliac vessels together with its bifurcation) can be curative in patients with metastasis or micrometastasis to a few nodes. Therefore, the procedure may be offered to all patients undergoing radical cystectomy for invasive bladder cancer.     

Pathologic Nodal Staging Scores in Patients Treated with Radical Prostatectomy: A Postoperative Decision Tool

Background

Nodal metastasis is the strongest risk factor of disease recurrence in patients with localized prostate cancer (PCa) treated with radical prostatectomy (RP).

Objective

To develop a model that allows quantification of the likelihood that a pathologically node-negative patient is indeed free of nodal metastasis.

Design, setting, and participants

Data from patients treated with RP and pelvic lymph node dissection (PLND; n = 7135) for PCa between 2000 and 2011 were analyzed. For external validation, we used data from patients (n = 4209) who underwent an anatomically defined extended PLND.

Intervention

RP and PLND.

Outcome measurements and statistical analysis

We developed a novel pathologic (postoperative) nodal staging score (pNSS) that represents the probability that a patient is correctly staged as node negative based on the number of examined nodes and the patient's characteristics.

Results and limitations

In the development and validation cohorts, the probability of missing a positive node decreases with an increasing number of nodes examined. Whereas in pT2 patients, a 90% pNSS was achieved with one single examined node in both the development and validation cohort, a similar level of nodal staging accuracy was achieved in pT3a patients by examining five and nine nodes, respectively. The pT3b/T4 patients achieved a pNSS of 80% and 70% when 17 and 20 nodes in the development and validation cohort were examined, respectively. This study is limited by its retrospective design and multicenter nature. The number of nodes removed was not directly correlated with the extent/template of PLND.

Conclusions

Every patient needs PLND for accurate nodal staging. However, a one-size-fits-all approach is too inaccurate. We developed a tool that indicates a node-negative patient is indeed free of lymph node metastasis by evaluating the number of examined nodes, pT stage, RP Gleason score, surgical margins, and prostate-specific antigen. This tool may help in postoperative decision making.     

A New Multimodality Technique Accurately Maps the Primary Lymphatic Landing Sites of the Bladder

Background

Pathoanatomic studies have failed to map accurately the primary lymphatic landing sites of the urinary bladder.

Objective

To use single-photon emission computed tomography (SPECT) combined with computed tomography (CT) plus intraoperative gamma probe verification to map the primary lymphatic landing sites of the bladder.

Design, setting, and participants

Clinical trial of 60 consecutive cystectomy patients at a single centre.

Intervention

Flexible cystoscopy-guided injection of technetium nanocolloid into one of six non-tumour-bearing sites of the bladder for preoperative detection of radioactive lymph nodes (LNs) with SPECT/CT followed by intraoperative verification with a gamma probe. Backup extended pelvic LN dissection (PLND) for ex vivo detection of missed LNs.

Measurements

Three-dimensional projection of each LN site.

Results and limitations

A median of 4 (range: 1–14) radioactive LNs were detected per site and patient. Ninety-two percent of all LNs were found distal and caudal to where the ureter crosses the common iliac arteries. Eight percent were found proximal to the uretero-iliac crossing, none without simultaneous detection of additional radioactive LNs within the endopelvic region. Extended PLND resected 92% of all primary lymphatic landing sites; limited PLND resected only 52%. A few LNs may have been missed despite preoperative SPECT/CT, intraoperative gamma probe verification, and extended backup PLND.

Conclusions

Multimodality SPECT/CT plus intraoperative gamma probe show the template of the bladder's primary lymphatic landing sites to be larger than is often thought. PLND limited to the ventral portion of the external iliac vessels and obturator fossa removes only about 50% of all primary lymphatic landing sites, whereas extended PLND along the major pelvic vessels, including the internal iliac, external iliac, obturator, and common iliac region up to the uretero-iliac crossing, removes about 90%.

Trial registration

ClinicalTrials.gov, ISRCTN39379749.     

Optimizing the Approach for Lymph Node Dissection during Laparoscopic Radical Cystectomy

Background

Lymph node dissection (LND) for muscle-invasive bladder cancer is one of the integral steps of radical cystectomy. In addition to staging, adequate LND has been found to alter both the prognosis for and the course of the disease after radical cystectomy.

Objective

To point out several essential steps that provide optimal exposure for LND during laparoscopic radical cystectomy for muscle-invasive bladder cancer.

Design, setting and participants

From August 2006 to September 2008, we performed 10 laparoscopic cystectomies with an extended LND using this approach at our institution. Patient and tumor characteristics, the anatomic extent of the LND, the number of lymph nodes examined, and the postoperative complications encountered were evaluated.

Surgical procedure

Essential steps include (1) a modified five-trocar arrangement; (2) use of a 30° telescope during LND; (3) prior complete mobilization of the sigmoid colon, allowing its retraction using an umbilical tape; (4) accomplishment of most of the bilateral LND from the right side; and (5) performance of LND after removal of the specimen.

Measurements

The primary end points were adequate intraoperative exposure of the template and number of lymph nodes retrieved. The secondary end point was evaluation of postoperative lymph node recurrence as an assessment of a complete LND.

Results and limitations

Mean total operative time was 512.5 min (range: 420–660), with a mean operative time of 143 min (range: 115–165) for the extended LND. Adequate exposure was successful in all 10 patients. The average number of lymph nodes examined was 25.5 (range: 19–32), with 4 nodes positive for metastasis. No patients had pelvic or lymph node metastasis at a mean follow-up of 14.8 mo (range: 4–30). Limitations included an analysis of a small series of patients.

Conclusions

This new approach provides optimal exposure for an adequate laparoscopic LND during radical cystectomy, without any compromise.     

Validation of the AJCC TNM Substaging of pT2 Bladder Cancer: Deep Muscle Invasion Is Associated with Significantly Worse Outcome

Background

The current TNM bladder cancer staging system stratifies bladder muscle invasion into superficial (pT2a) and deep (pT2b). Controversy exists regarding the significance of the extent of muscle invasion on clinical outcome.

Objective

Our aim was to compare the cancer-specific outcomes of patients with pT2 urothelial carcinoma of the bladder (UCB) at radical cystectomy (RC) in a large international cohort of patients.

Design, setting, and participants

The records of patients treated with RC for UCB at six centers were reviewed. Of the 2605 reviewed patients, 565 (21.7%) had pT2 disease. None of the patients received preoperative systemic chemotherapy or radiotherapy.

Measurements

Patients’ characteristics and outcome were evaluated.

Results and limitations

The median patient age in the entire group was 66.2 yr. Of the 565 patients with pT2 UCB, 249 patients (44.1%) had substage pT2a; 316 patients (55.9%) had pT2b. One hundred and eleven patients (19.6%) had metastases to regional lymph nodes. Median follow-up was 50.5 mo. Recurrence-free survival (73.2% vs 58.7%) and cancer-specific survival (78.0% vs 65.1%) estimates were significantly better for pT2a patients compared with those with pT2b (p = 0.002 and p = 0.001, respectively). Pathologic T2 substaging was associated with worse recurrence-free and cancer-specific survival after adjusting for the effects of standard pathologic features (p = 0.011 and p = 0.006, respectively). The statistical significance of these associations was reconfirmed in subgroup analysis limited to those patients with pathologically negative lymph nodes.

Conclusions

In this large international cohort, pathologic substaging helped to stratify patients with lymph node–negative pT2 UCB into statistically significantly different risk groups. These data support the value of the current American Joint Committee on Cancer TNM staging.     

Diagnosis and treatment of lymph node metastases in pediatric rhabdomyosarcoma in the Netherlands: A retrospective analysis

Background

In pediatric rhabdomyosarcoma (RMS), evaluation of lymph node involvement (N1) is an important staging aspect, but difficult to assess. The aim of our study was to evaluate the assessment of lymph node infiltration and impact on outcome in N1 RMS patients.

Methods

We identified 277 non-metastatic RMS patients diagnosed and treated between 1990 and 2008. Patients with recorded N1 disease were evaluated for their diagnostic procedures and outcome.

Results

In 13.7% N1 status was reported. In 19 of 34 N1 patients, lymph node biopsies were performed for histologically confirmation. Different treatment modalities were used to treat lymph node metastases. In total 23 of 31 patients received local treatment of the node (11/23 RT, 4/23 surgery, and 8/23 both). All patients received chemotherapy. Lymph node relapse occurred in 7 of 31 patients who were treated with one or two modalities. Only 1 (14%) of 8 patients treated with three modalities relapsed. In N0 patients 10 (4.2%) of 239 had a regional lymph node relapse, and 9 of 10 died.

Conclusion

Lymph node metastases are an essential part of staging. Node positivity contributes to relapse of disease. Nodal relapse is also associated with a high mortality rate. These data imply that nodal assessment needs to be optimal and standardized for improved staging.     

Robotic-Assisted Laparoscopic Extended Pelvic Lymph Node Dissection for Prostate Cancer: Surgical Technique and Experience with the First 99 Cases

Background

To date, there is still a paucity of data in the literature on robotic-assisted laparoscopic extended pelvic lymph node dissection (RALEPLND) in patients with prostate cancer.

Objective

To assess the technical feasibility of RALEPLND and to present our surgical technique.

Design, setting, and participants

From April 2006 to March 2008, we performed RALEPLND in 99 patients prior to robotic-assisted laparoscopic radical prostatectomy. Indications for RALEPLND were a prostate-specific antigen (PSA) ≥10 ng/ml or a preoperative Gleason score ≥7. The data were evaluated retrospectively.

Surgical procedure

The transperitoneal approach was used in all cases. In order to gain optimal access to the common iliac bifurcation, the five trocars were placed in a more cephalad position than in patients undergoing radical prostatectomy without RALEPLND. After identification of important landmarks, the lymphatics covering the external iliac vein, the obturator lymphatic packet, and the lymphatics overlying the internal iliac artery were removed on both sides.

Measurements

The total lymph node yield, the frequency of lymph node metastases, and the complication rate.

Results and limitations

The median patient age was 64 yr (range: 45–78). The median preoperative PSA level was 7.7 ng/ml (range: 1.5–84.6). The median number of lymph nodes harvested was 19 (range: 8–53). In 16 patients (16%), we found lymph node metastasis. Complications occurred in seven patients (7%).

Conclusions

RALEPLND is feasible, and its lymph node yield is well in the range of open series. The robotic-assisted laparoscopic approach in itself does not seem to limit a surgeon's ability to perform a complete extended pelvic lymph node dissection.