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European Journal of Nuclear Medicine... Aug 2023To develop and evaluate a lymph node invasion (LNI) prediction model for men staged with [Ga]Ga-PSMA-11 PET.
Development and external validation of a multivariable [Ga]Ga-PSMA-11 PET-based prediction model for lymph node involvement in men with intermediate or high-risk prostate cancer.
PURPOSE
To develop and evaluate a lymph node invasion (LNI) prediction model for men staged with [Ga]Ga-PSMA-11 PET.
METHODS
A consecutive sample of intermediate to high-risk prostate cancer (PCa) patients undergoing [Ga]Ga-PSMA-11 PET, extended pelvic lymph node dissection (ePLND), and radical prostatectomy (RP) at two tertiary referral centers were retrospectively identified. The training cohort comprised 173 patients (treated between 2013 and 2017), the validation cohort 90 patients (treated between 2016 and 2019). Three models for LNI prediction were developed and evaluated using cross-validation. Optimal risk-threshold was determined during model development. The best performing model was evaluated and compared to available conventional and multiparametric magnetic resonance imaging (mpMRI)-based prediction models using area under the receiver operating characteristic curves (AUC), calibration plots, and decision curve analysis (DCA).
RESULTS
A combined model including prostate-specific antigen, biopsy Gleason grade group, [Ga]Ga Ga-PSMA-11 positive volume of the primary tumor, and the assessment of the [Ga]Ga-PSMA-11 report N-status yielded an AUC of 0.923 (95% CI 0.863-0.984) in the external validation. Using a cutoff of ≥ 17%, 44 (50%) ePLNDs would be spared and LNI missed in one patient (4.8%). Compared to conventional and MRI-based models, the proposed model showed similar calibration, higher AUC (0.923 (95% CI 0.863-0.984) vs. 0.700 (95% CI 0.548-0.852)-0.824 (95% CI 0.710-0.938)) and higher net benefit at DCA.
CONCLUSIONS
Our results indicate that information from [Ga]Ga-PSMA-11 may improve LNI prediction in intermediate to high-risk PCa patients undergoing primary staging especially when combined with clinical parameters. For better LNI prediction, future research should investigate the combination of information from both PSMA PET and mpMRI for LNI prediction in PCa patients before RP.
Topics: Male; Humans; Gallium Radioisotopes; Prostatic Neoplasms; Retrospective Studies; Lymph Nodes; Lymph Node Excision; Prostatectomy; Positron Emission Tomography Computed Tomography
PubMed: 37261472
DOI: 10.1007/s00259-023-06278-1 -
Journal of Gynecologic Oncology May 2023Cervical cancer is still present a major public health problem, especially in developing countries. In International Federation of Gynaecology and Obstetrics 2018,...
BACKGROUND
Cervical cancer is still present a major public health problem, especially in developing countries. In International Federation of Gynaecology and Obstetrics 2018, allowing assessment of retroperitoneal lymph nodes by imaging and/or pathological findings and, if deemed metastatic, the case is designated as stage IIIC (with r and p notations). Patients with lymph node metastases have lower overall survival (OS), progression free survival (PFS), and survival after recurrence, especially those who have unresectable macroscopical positive lymph nodes. Retrospective analysis suggests that there may be a benefit to debulking macroscopic nodes that would be otherwise difficult to sterilize with standard doses of radiation therapy. However, there are no prospective study reporting that resecting macroscopic nodes before concurrent chemoradiation therapy (CCRT) would improve PFS or OS of cervical cancer and no guidelines for surgical resection of bulky lymph nodes. The CQGOG0103 study is a prospective, multicenter and randomized controlled trial (RCT) evaluating lymph node dissection on stage IIICr of cervical cancer.
METHODS
Eligible patients are histologically confirmed cervical squamous cell carcinoma, adenocarcinoma, adeno-squamous cell carcinoma. Stage IIICr (confirmed by computed tomography [CT]/magnetic resonance imaging/positron emission tomography/CT) and the short diameter of image-positive lymph node ≥15 mm. 452 patients will be equally randomized to receive either CCRT (pelvic external-beam radiotherapy [EBRT]/extended-field EBRT + cisplatin [40 mg/m²] or carboplatin [the area under curve=2] every week for 5 cycles + brachytherapy) or open/minimally invasive pelvic and para-aortic lymph node dissection followed by CCRT. Randomization is stratified by status of para-aortic lymph node. The primary endpoint is PFS. Secondary endpoints are OS and surgical complications. A total of 452 patients will be enrolled from multiple hospitals in China within 4 years and followed up for 5 years.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04555226.
Topics: Female; Humans; Uterine Cervical Neoplasms; Lymph Node Excision; Lymph Nodes; Chemoradiotherapy; Adenocarcinoma; Retrospective Studies; Neoplasm Staging; Randomized Controlled Trials as Topic; Multicenter Studies as Topic; Clinical Trials, Phase III as Topic
PubMed: 36998225
DOI: 10.3802/jgo.2023.34.e55 -
BMC Cancer Jul 2020Systematic retroperitoneal lymphadenectomy has been widely used in the surgical treatment of advanced ovarian cancer patients. Nevertheless, the corresponding...
BACKGROUND
Systematic retroperitoneal lymphadenectomy has been widely used in the surgical treatment of advanced ovarian cancer patients. Nevertheless, the corresponding therapeutic may not provide a survival benefit. The aim of this study was to assess the effect of systematic retroperitoneal lymphadenectomy in such patients.
METHODS
Patients with advanced ovarian cancer (stage III-IV, according to the classification presented by the International Federation of Gynecology and Obstetrics) who were admitted and treated in Zhejiang Cancer Hospital from January 2004 to December 2013 were enrolled and reviewed retrospectively. All patients were optimally or suboptimally debulked (absent or residual tumor < 1 cm) and divided into two groups. Group A (no-lymphadenectomy group, n = 170): patients did not undergo lymph node resection; lymph nodes resection or biopsy were selective. Group B (n = 240): patients underwent systematic retroperitoneal lymphadenectomy.
RESULTS
A total of 410 eligible patients were enrolled in the study. The patients' median age was 51 years old (range, 28-72 years old). The 5-year overall survival (OS) and 2-year progression-free survival (PFS) rates were 78 and 24% in the no-lymphadenectomy group and 76 and 26% in the lymphadenectomy group (P = 0.385 and 0.214, respectively). Subsequently, there was no significant difference in 5-year OS and 2-year PFS between the two groups stratified to histological types (serous type or non-serous type), the clinical evaluation of negative lymph nodes or with macroscopic peritoneal metastasis beyond pelvic (IIIB-IV). Multivariate Cox regression analysis indicated that systematic retroperitoneal lymphadenectomy was not a significant factor influencing the patients' survival. Patients in the lymphadenectomy group had a higher incidence of postoperative complications (incidence of infection treated with antibiotics was 21.7% vs. 12.9% [P = 0.027]; incidence of lymph cysts was 20.8% vs. 2.4% [P < 0.001]).
CONCLUSIONS
Our study showed that systematic retroperitoneal lymphadenectomy did not significantly improve survival of advanced ovarian cancer patients with residual tumor < 1 cm or absent after cytoreductive surgery, and were associated with a higher incidence of postoperative complications.
Topics: Adenocarcinoma, Clear Cell; Adenocarcinoma, Mucinous; Adult; Aged; Cystadenocarcinoma, Serous; Cytoreduction Surgical Procedures; Endometrial Neoplasms; Female; Follow-Up Studies; Humans; Lymph Node Excision; Lymphatic Metastasis; Middle Aged; Neoplasm, Residual; Ovarian Neoplasms; Peritoneal Neoplasms; Prognosis; Retroperitoneal Space; Retrospective Studies; Survival Rate
PubMed: 32660444
DOI: 10.1186/s12885-020-07144-1 -
Urologic Oncology Nov 2022Extended Pelvic Lymph Node Dissection (ePLND) remains the most accurate technique for the detection of occult lymph node metastases (LNMs) in prostate cancer (CaP)...
INTRODUCTION AND OBJECTIVES
Extended Pelvic Lymph Node Dissection (ePLND) remains the most accurate technique for the detection of occult lymph node metastases (LNMs) in prostate cancer (CaP) patients. Here we aim to examine whether free-Indocyanine Green (F-ICG) could accurately assess the pathological nodal (pN) status in CaP patients during real-time lymphangiography as a potential replacement for ePLND.
MATERIALS AND METHODS
219 consecutive patients undergoing F-ICG-guided PLND, ePLND and radical prostatectomy (RP) for clinical-localized CaPwere included in this prospective single-center study. The pathological outcomes of F-ICG-guided PLND were compared to confirmatory ePLND. Parameters of a binary diagnostic test for the proper classification of the pN status of patients ('per-patient' analysis) and for the probability of detecting all the metastatic LNs ('per-node' analysis) were calculated. Outcome measures were prevalence, accuracy (Acc), sensitivity (Se), negative predictive value (NPV), and likelihood ratio of a negative F-ICG-guided PLND test result [LR(-)].
RESULTS
F-ICG-guided PLND successfully visualized LNs in all procedures with no adverse events. The overall per-patient F-ICG staging Acc was 97.7%, Se was 91.4%, with a NPV of 97.0%, and LR(-) of 8.6%. At the overall per-node level, 4,780 LNs were removed and 1,535 (32.1%) were fluorescent in vivo. F-ICG-guided PLND identified LNMs with a Se of 63.4%.
CONCLUSIONS
This study confirms that F-ICG-guided lymphangiography correctly staged almost 98% of patients. The high per-patient NPV suggested that avoiding ePLND is safe for most patients when F-ICG stained nodes were pN0. Thus, more conservative approaches might minimise perioperative morbidity during LNMs diagnosis in selected patients.
Topics: Male; Humans; Indocyanine Green; Prospective Studies; Lymph Nodes; Pelvis; Prostatectomy; Lymph Node Excision; Lymphatic Metastasis; Prostatic Neoplasms
PubMed: 36175317
DOI: 10.1016/j.urolonc.2022.08.005 -
International Journal of Environmental... Mar 2022In endometrial carcinoma (EC) patients, sentinel lymph node (SLN) biopsy has shown the potential to reduce post-operative morbidity and long-term complications, and to... (Review)
Review
BACKGROUND
In endometrial carcinoma (EC) patients, sentinel lymph node (SLN) biopsy has shown the potential to reduce post-operative morbidity and long-term complications, and to improve the detection of low-volume metastasis through ultrastaging. However, while it has shown high sensitivity and feasibility in low-risk EC patient groups, its role in high-risk groups is still unclear.
AIM
To assess the role of SLN biopsy through the cervical injection of indocyanine green (ICG) in high-risk groups of early-stage EC patients.
MATERIALS AND METHODS
Seven electronic databases were searched from their inception to February 2021 for studies that allowed data extraction about detection rate and accuracy of SLN biopsy through the cervical injection of ICG in high-risk groups of early-stage EC patients. We calculated pooled sensitivity, false negative (FN) rate, detection rate of SLN per hemipelvis (DRh), detection rate of SLN per patients (DRp), and bilateral detection rate of SLN (DRb), with 95% confidence interval (CI).
RESULTS
Five observational cohort studies (three prospective and two retrospective) assessing 578 high risk EC patients were included. SLN biopsy sensitivity in detecting EC metastasis was 0.90 (95% CI: 0.03-0.95). FN rate was 2.8% (95% CI: 0.6-11.6%). DRh was 88.4% (95% CI: 86-90.5%), DRp was 96.6% (95% CI: 94.7-97.8%), and DRb was 80% (95% CI: 75.4-83.9).
CONCLUSION
SLN biopsy through ICG cervical injection may be routinely adopted instead of systematic pelvic and para-aortic lymphadenectomy in surgical staging for high-risk groups of early-stage EC patients, as well as in low-risk groups.
Topics: Coloring Agents; Endometrial Neoplasms; Female; Humans; Indocyanine Green; Lymph Node Excision; Lymphatic Metastasis; Neoplasm Staging; Prospective Studies; Retrospective Studies; Sentinel Lymph Node Biopsy
PubMed: 35329403
DOI: 10.3390/ijerph19063716 -
Medicina (Kaunas, Lithuania) Oct 2022: Pelvic lymphadenectomy has been associated with radical hysterectomy for the treatment of early Cervical Cancer (ECC) since 1905. However, some complications are... (Meta-Analysis)
Meta-Analysis Review
: Pelvic lymphadenectomy has been associated with radical hysterectomy for the treatment of early Cervical Cancer (ECC) since 1905. However, some complications are related to this technique, such as lymphedema and nerve damage. In addition, its clinical role is controversial. For this reason, the sentinel lymph node (SLN) has found increasing use in clinical practice over time. Oncologic safety, however, is debated, and there is no clear evidence in the literature regarding this. Therefore, our meta-analysis aims to schematically analyze the current scientific evidence to investigate the non-inferiority of SLN versus PLND regarding oncologic outcomes. : Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched the PubMed and Scopus databases in June 2022 since their early first publications. We made no restrictions on the country. We considered only studies entirely published in English. We included studies containing Disease-Free Survival (DFS), Overall Survival (OS), Recurrence Rate (RR), and site of recurrence data. We used comparative studies for meta-analysis. We registered this meta-analysis to the PROSPERO site for meta-analysis with protocol number CRD42022316650. : Twelve studies fulfilled inclusion criteria. The four comparative studies were enrolled in meta-analysis. Patients were analyzed concerning Sentinel Lymph Node Biopsy (SLN) and compared with Bilateral Pelvic Systematic Lymphadenectomy (PLND) in early-stage Cervical Cancer (ECC). Meta-analysis highlighted no differences in oncological safety between these two techniques, both in DFS and OS. Moreover, most of the sites of recurrences in the SLN group seemed not to be correlated with missed lymphadenectomy. : Data in the literature do not seem to show clear oncologic inferiority of SLN over PLND. On the contrary, the higher detection rate of positive lymph nodes and the predominance of no lymph node recurrences give hope that this technique may equal PLND in oncologic terms, improving its morbidity profile.
Topics: Female; Humans; Sentinel Lymph Node; Uterine Cervical Neoplasms; Sentinel Lymph Node Biopsy; Lymph Node Excision; Lymph Nodes; Neoplasm Staging
PubMed: 36363496
DOI: 10.3390/medicina58111539 -
European Journal of Surgical Oncology :... Nov 2021To investigate surgical complications related to the staging procedure for endometrial cancer (EC) and to explore complication associations towards patient...
OBJECTIVE
To investigate surgical complications related to the staging procedure for endometrial cancer (EC) and to explore complication associations towards patient characteristics and survival.
METHODS
A population-based cohort study of women diagnosed with EC where primary surgery was performed at a tertiary centre between 2012 and 2016. The Swedish Quality Registry for Gynecological Cancer was used for identification, medical records reviewed and surgical outcomes, including complications according to Clavien-Dindo (CD), and comorbidity (Charlson's index) registered. Uni- and multivariable logistic regression analyses were performed with complications as outcome and multivariable Cox regression analysis with overall survival (OS) as endpoint.
RESULTS
In total 549 women were identified where 108 (19.7%) had CD grade II-V complications. In the multivariable regression analysis; surgical technique, BMI and lymph node dissection, but not comorbidity or age, were found to be risk factors for complications CD grade II-V, with OR of 0.32 (95%CI:0.18-0.56) for minimalinvasive surgery (MIS) compared to open, OR 2.18 (95%CI:1.37-3.49) for BMI ≥30 and OR 2.63 (95%CI:1.32-5.31) for pelvic and paraaortic lymphnode dissection. In Cox regression analysis, a significant lower OS was found within the first 1.5 years for the cohort of complications (CD II-V) compared to no complications.
CONCLUSION
Surgical staging with lymphadenectomy was found a risk factor for complications together with high BMI in EC. Using MIS was significantly associated with less complications. Overall survival was found to be negatively affected within the first years after complications. Our results may be taken into consideration when performing updated treatment guidelines including surgical staging.
Topics: Adult; Aged; Aged, 80 and over; Endometrial Neoplasms; Female; Humans; Laparotomy; Lymph Node Excision; Middle Aged; Neoplasm Staging; Obesity; Postoperative Complications; Registries; Survival Rate; Sweden
PubMed: 34238643
DOI: 10.1016/j.ejso.2021.06.034 -
Prostate Cancer and Prostatic Diseases Jun 2021Lymph-node (LN) metastasis in prostate cancer (PC) is a main risk factor for tumor recurrence after radical prostatectomy (RP). Molecular analysis facilitates detection...
BACKGROUND
Lymph-node (LN) metastasis in prostate cancer (PC) is a main risk factor for tumor recurrence after radical prostatectomy (RP). Molecular analysis facilitates detection of small-volume LN metastases with higher sensitivity than histopathology. We aimed to prospectively evaluate six candidate gene markers for detection of pelvic LN metastases and to determine their ability to predict biochemical recurrence-free survival (bRFS) in patients treated with RP.
METHODS
The expression of kallikrein 2, 3, and 4 (KLK2, KLK3, and KLK4), prostate-specific membrane antigen (PSMA), transmembrane serine protease 2 (TMPRSS2) and transient receptor potential cation channel subfamily M member 8 (TRPM8) was assessed using qPCR. We analyzed LNs from 111 patients (intermediate PC, n = 32 (29%); high-risk PC, n = 79 (71%)) who underwent RP and extended pelvic lymph-node dissection without neoadjuvant treatment.
RESULTS
Overall, 2411 LNs were examined by molecular and histopathologic examination. Histopathology detected 69 LN metastases in 28 (25%) patients. KLK2 and KLK3 diagnostically performed best and classified all pN1-patients correctly as molecular node-positive (molN1/pN1). The concordance on LN level was best for KLK3 (96%). KLK2, KLK3, KLK4, PSMA, TMPRSS2, and TRPM8 reclassified 27 (24%), 32 (29%), 29 (26%), 8 (7%), 13 (12%), and 23 (21%) pN0-patients, respectively, as node-positive (pN0/molN1). On multivariable cox regression analysis molecular LN status (molN1 vs. molN0) using KLK3 (HR 4.0, p = 0.04) and TMPRSS2 (HR 5.1, p = 0.02) were independent predictors of bRFS. Median bRFS was shorter in patients with only molecular positive LNs (molN1/pN0) for KLK3 (24 months, p = 0.001) and for TMPRSS2 (12 months, p < 0.001) compared to patients with negative nodes (molN0/pN0) (median bRFS not reached).
CONCLUSIONS
For diagnostic purposes, KLK3 showed highest concordance with histopathology for detection of LN metastases in PC patients undergoing RP. For prognostic purposes, KLK3 and TMPRSS2 expression were superior to histopathologic LN status and other transcripts tested for molecular LN status. We suggest a combined KLK3/TMPRSS2 panel as a valuable diagnostic and prognostic tool for molecular LN analysis.
Topics: Aged; Biomarkers, Tumor; Follow-Up Studies; Humans; Kallikreins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Neoplasm Recurrence, Local; Prognosis; Prospective Studies; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Serine Endopeptidases; Survival Rate
PubMed: 32978525
DOI: 10.1038/s41391-020-00283-3 -
Frontiers in Oncology 2021To evaluate the role of sentinel lymph node biopsy (SLNB) to avoid staging lymphadenectomies by detecting nodal metastasis in intermediate- and high-risk endometrial...
OBJECTIVE
To evaluate the role of sentinel lymph node biopsy (SLNB) to avoid staging lymphadenectomies by detecting nodal metastasis in intermediate- and high-risk endometrial cancer (EC).
METHODS
A single institutional retrospective study was performed including all patients with intermediate- and high-risk EC who underwent surgical nodal staging between January 2012 and December 2019. Patients with disseminated disease detected on imaging techniques or at the time of surgery were excluded. Patients were evaluable if they underwent nodal staging with SLNB and pelvic (PLD) and paraaortic (PALD) lymph node dissection. We analyzed the accuracy of the sentinel lymph node technique. Only patients with at least one sentinel lymph node (SLN) detected were included in the sensitivity and negative predictive value (NPV) analyses. The tracers used were technetium 99m, blue dye, and indocyanine green.
RESULTS
Eighty-eight patients presented intermediate- and high-risk EC (51 patients and 37 patients respectively) and underwent SLNB with consecutive PLD and PALD. The median (range) number of sentinel nodes retrieved was 2.9 (0-11). The global detection rate of SLN was 96.6% with a bilateral detection of 80.7% when considering all tracers used. However, when combination of indocyanine green and technetium was used the bilateral detection rate was 90.3%. Nodal metastases were detected in 17 (19.3%) cases, 8 (47%) of them corresponded to low volume metastasis (LVM), 7 (87.5%) of them diagnosed at ultrastaging pathologic exam. Finally, we obtained a sensitivity of 90%, a NPV of 97.5%, and a false negative rate (FNR) of 10% in the intermediate-risk EC compared to sensitivity of 85.7%, NPV of 96.6%, and FNR of 14.3% in the high-risk EC group. The only patient with isolated paraaortic nodal metastasis was found at the high-risk group, 1.1%.
CONCLUSIONS
According to our results, full lymphadenectomy could be avoided by performing SLNB in patients with intermediate-risk EC because the only false negative case detected was at the beginning of ICG learning curve. For high-risk EC patients we did not find enough evidence to support the systematic avoidance of staging full lymph node dissection. Nevertheless, SLNB should be performed in all cases of EC as it improves LVM diagnosis substantially.
PubMed: 33937061
DOI: 10.3389/fonc.2021.654285 -
Translational Andrology and Urology Dec 2020The full optimal extent of a pelvic lymph node dissection (PLND) at time of radical cystectomy (RC) has not yet been determined. The diagnostic role of LND is clear and... (Review)
Review
The full optimal extent of a pelvic lymph node dissection (PLND) at time of radical cystectomy (RC) has not yet been determined. The diagnostic role of LND is clear and is extremely important for identifying those who may benefit from adjuvant therapy. While retrospective analyses have demonstrated improved survival when the number of lymph nodes is increased and extended LNDs (eLNDs) are performed, these results have yet to be borne out in prospective randomized phase III trials. The recently published LEA AUO AB 25/02 trial is a promising attempt to determine the efficacy of eLND, but unfortunately falls short because of its limited design and therefore, did not demonstrate an improvement in recurrence-free survival (RFS). In an era of increased utilization of neoadjuvant chemotherapy (NAC) providing survival benefit, the ability to demonstrate improved survival with eLND is even more challenging. Currently, we are awaiting the results of SWOG S1011, expectations of achieving a positive trial with improved RFS remains unlikely.
PubMed: 33457268
DOI: 10.21037/tau-20-406