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JAMA Oncology Nov 2021The presence of pelvic nodal metastases at radical prostatectomy is associated with biochemical recurrence after prostatectomy.
Diagnostic Accuracy of 68Ga-PSMA-11 PET for Pelvic Nodal Metastasis Detection Prior to Radical Prostatectomy and Pelvic Lymph Node Dissection: A Multicenter Prospective Phase 3 Imaging Trial.
IMPORTANCE
The presence of pelvic nodal metastases at radical prostatectomy is associated with biochemical recurrence after prostatectomy.
OBJECTIVE
To assess the accuracy of prostate-specific membrane antigen (PSMA) 68Ga-PSMA-11 positron emission tomographic (PET) imaging for the detection of pelvic nodal metastases compared with histopathology at time of radical prostatectomy and pelvic lymph node dissection.
DESIGN, SETTING, AND PARTICIPANTS
This investigator-initiated prospective multicenter single-arm open-label phase 3 imaging trial of diagnostic efficacy enrolled 764 patients with intermediate- to high-risk prostate cancer considered for prostatectomy at University of California, San Francisco and University of California, Los Angeles from December 2015 to December 2019. Data analysis took place from October 2018 to July 2021.
INTERVENTIONS
Imaging scan with 3 to 7 mCi of 68Ga-PSMA-11 PET.
MAIN OUTCOMES AND MEASURES
The primary end point was the sensitivity and specificity for the detection pelvic lymph nodes compared with histopathology on a per-patient basis using nodal region correlation. Each scan was read centrally by 3 blinded independent central readers, and a majority rule was used for analysis.
RESULTS
A total of 764 men (median [interquartile range] age, 69 [63-73] years) underwent 1 68Ga-PSMA-11 PET imaging scan for primary staging, and 277 of 764 (36%) subsequently underwent prostatectomy with lymph node dissection (efficacy analysis cohort). Based on pathology reports, 75 of 277 patients (27%) had pelvic nodal metastasis. Results of 68Ga-PSMA-11 PET were positive in 40 of 277 (14%), 2 of 277 (1%), and 7 of 277 (3%) of patients for pelvic nodal, extrapelvic nodal, and bone metastatic disease. Sensitivity, specificity, positive predictive value, and negative predictive value for pelvic nodal metastases were 0.40 (95% CI, 0.34-0.46), 0.95 (95% CI, 0.92-0.97), 0.75 (95% CI, 0.70-0.80), and 0.81 (95% CI, 0.76-0.85), respectively. Of the 764 patients, 487 (64%) did not undergo prostatectomy, of which 108 were lost to follow-up. Patients with follow-up instead underwent radiotherapy (262 of 379 [69%]), systemic therapy (82 of 379 [22%]), surveillance (16 of 379 [4%]), or other treatments (19 of 379 [5%]).
CONCLUSIONS AND RELEVANCE
This phase 3 diagnostic efficacy trial found that in men with intermediate- to high-risk prostate cancer who underwent radical prostatectomy and lymph node dissection, the sensitivity and specificity of 68Ga-PSMA-11 PET were 0.40 and 0.95, respectively. This academic collaboration is the largest known to date and formed the foundation of a New Drug Application for 68Ga-PSMA-11.
TRIAL REGISTRATION
ClinicalTrials.gov Identifiers: NCT03368547, NCT02611882, and NCT02919111.
Topics: Aged; Gallium Isotopes; Gallium Radioisotopes; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prospective Studies; Prostate; Prostatectomy; Prostatic Neoplasms
PubMed: 34529005
DOI: 10.1001/jamaoncol.2021.3771 -
The New England Journal of Medicine Feb 2019Systematic pelvic and paraaortic lymphadenectomy has been widely used in the surgical treatment of patients with advanced ovarian cancer, although supporting evidence... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Systematic pelvic and paraaortic lymphadenectomy has been widely used in the surgical treatment of patients with advanced ovarian cancer, although supporting evidence from randomized clinical trials has been limited.
METHODS
We intraoperatively randomly assigned patients with newly diagnosed advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage IIB through IV) who had undergone macroscopically complete resection and had normal lymph nodes both before and during surgery to either undergo or not undergo lymphadenectomy. All centers had to qualify with regard to surgical skills before participation in the trial. The primary end point was overall survival.
RESULTS
A total of 647 patients underwent randomization from December 2008 through January 2012, were assigned to undergo lymphadenectomy (323 patients) or not undergo lymphadenectomy (324), and were included in the analysis. Among patients who underwent lymphadenectomy, the median number of removed nodes was 57 (35 pelvic and 22 paraaortic nodes). The median overall survival was 69.2 months in the no-lymphadenectomy group and 65.5 months in the lymphadenectomy group (hazard ratio for death in the lymphadenectomy group, 1.06; 95% confidence interval [CI], 0.83 to 1.34; P = 0.65), and median progression-free survival was 25.5 months in both groups (hazard ratio for progression or death in the lymphadenectomy group, 1.11; 95% CI, 0.92 to 1.34; P = 0.29). Serious postoperative complications occurred more frequently in the lymphadenectomy group (e.g., incidence of repeat laparotomy, 12.4% vs. 6.5% [P = 0.01]; mortality within 60 days after surgery, 3.1% vs. 0.9% [P = 0.049]).
CONCLUSIONS
Systematic pelvic and paraaortic lymphadenectomy in patients with advanced ovarian cancer who had undergone intraabdominal macroscopically complete resection and had normal lymph nodes both before and during surgery was not associated with longer overall or progression-free survival than no lymphadenectomy and was associated with a higher incidence of postoperative complications. (Funded by Deutsche Forschungsgemeinschaft and the Austrian Science Fund; LION ClinicalTrials.gov number, NCT00712218.).
Topics: Adult; Aged; Aged, 80 and over; CA-125 Antigen; Female; Humans; Kaplan-Meier Estimate; Lymph Node Excision; Lymphatic Metastasis; Middle Aged; Operative Time; Ovarian Neoplasms; Postoperative Complications; Progression-Free Survival; Proportional Hazards Models; Survival Rate; Treatment Failure; Young Adult
PubMed: 30811909
DOI: 10.1056/NEJMoa1808424 -
The Indian Journal of Medical Research Aug 2021Surgery plays an important role in the management of early-stage cervical cancer. Type III radical hysterectomy with bilateral pelvic lymph node dissection using open... (Review)
Review
Surgery plays an important role in the management of early-stage cervical cancer. Type III radical hysterectomy with bilateral pelvic lymph node dissection using open route is the standard surgical procedure. There is level I evidence against the use of laparoscopic/robotic approach for radical hysterectomy for cervical cancer. Emerging data support the use of sentinel lymph node biopsy and nerve sparing radical hysterectomy in carefully selected patients with early-stage disease. In locally advanced cervical cancer patients, the use of neoadjuvant chemotherapy (NACT) followed by radical surgery yields inferior disease-free survival compared to definitive concurrent chemoradiation therapy. Therefore, definitive concurrent chemoradiation is the standard treatment for locally advanced disease. Fertility preserving surgery is feasible in highly selected young patients. Role of less-radical surgical procedures in patients' with low-stage disease with good prognostic factors is under evaluation.
Topics: Consensus; Female; Humans; Hysterectomy; Lymph Node Excision; Neoadjuvant Therapy; Neoplasm Staging; Uterine Cervical Neoplasms
PubMed: 34854431
DOI: 10.4103/ijmr.IJMR_4240_20 -
European Urology Jul 2017There is controversy regarding the therapeutic role of pelvic lymph node dissection (PLND) in patients undergoing radical prostatectomy for prostate cancer (PCa). (Review)
Review
CONTEXT
There is controversy regarding the therapeutic role of pelvic lymph node dissection (PLND) in patients undergoing radical prostatectomy for prostate cancer (PCa).
OBJECTIVE
To systematically review the relevant literature assessing the relative benefits and harms of PLND for oncological and non-oncological outcomes in patients undergoing radical prostatectomy for PCa.
EVIDENCE ACQUISITION
MEDLINE, MEDLINE In-Process, Embase, and the Cochrane Central Register of Controlled Trials were searched up to December 2015. Comparative studies evaluating no PLND, limited, standard, and (super)-extended PLND that reported oncological and non-oncological outcomes were included. Risk-of-bias and confounding assessments were performed. A narrative synthesis was undertaken.
EVIDENCE SYNTHESIS
Overall, 66 studies recruiting a total of 275,269 patients were included (44 full-text articles and 22 conference abstracts). Oncological outcomes were addressed by 29 studies, one of which was a randomized clinical trial (RCT). Non-oncological outcomes were addressed by 43 studies, three of which were RCTs. There were high risks of bias and confounding in most studies. Conflicting results emerged when comparing biochemical and clinical recurrence, while no significant differences were observed among groups for survival. Conversely, the majority of studies showed that the more extensive the PLND, the greater the adverse outcomes in terms of operating time, blood loss, length of stay, and postoperative complications. No significant differences were observed in terms of urinary continence and erectile function recovery.
CONCLUSIONS
Although representing the most accurate staging procedure, PLND and its extension are associated with worse intraoperative and perioperative outcomes, whereas a direct therapeutic effect is still not evident from the current literature. The current poor quality of evidence indicates the need for robust and adequately powered clinical trials.
PATIENT SUMMARY
Based on a comprehensive review of the literature, this article summarizes the benefits and harms of removing lymph nodes during surgery to remove the prostate because of PCa. Although the quality of the data from the studies was poor, the review suggests that lymph node removal may not have any direct benefit on cancer outcomes and may instead result in more complications. Nevertheless, the procedure remains justified because it enables accurate assessment of cancer spread.
Topics: Adult; Aged; Aged, 80 and over; Disease-Free Survival; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Grading; Neoplasm Staging; Odds Ratio; Postoperative Complications; Prostatectomy; Prostatic Neoplasms; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 28126351
DOI: 10.1016/j.eururo.2016.12.003 -
European Journal of Cancer (Oxford,... Jul 2019To prospectively assess the diagnostic accuracy of a pelvic sentinel lymph node (SLN) algorithm in high-risk endometrial cancer (HREC). (Clinical Trial)
Clinical Trial
STUDY AIMS
To prospectively assess the diagnostic accuracy of a pelvic sentinel lymph node (SLN) algorithm in high-risk endometrial cancer (HREC).
PATIENTS AND METHODS
Consecutive women with presumed FIGO stage I-II HREC underwent robotic surgery at two academic centres by five accredited surgeons. An anatomically based algorithm was adhered to, following cervical injection of indocyanine green (ICG), with reinjection of tracer in case of non-display of predefined lymphatic pathways. After removal of SLNs, a pelvic and infrarenal para-aortic lymphadenectomy was performed. Primary end-point was sensitivity of the SLN-ICG algorithm. Secondary end-points were sensitivity of the overall SLN algorithm (including macroscopically suspect nodes as SLNs), SLN mapping rates and morbidity of the SLN procedure.
RESULTS
Two hundred fifty-seven women were analysed; 54 had pelvic lymph node metastases (LNMs), and 52 of those were correctly identified by the SLN-ICG algorithm. In two women (one with false-negative ICG-SLNs and one non-mapped woman), the pelvic LNMs were identified by the overall SLN algorithm. The SLN-ICG algorithm had a sensitivity of 98% (95% confidence interval [CI] 89-100) and a negative predictive value of 99.5% (95% CI 97-100). The sensitivity of the overall SLN algorithm was 100% (95% CI 92-100) and the negative predictive value was 100% (95% CI 98-100). The bilateral mapping rate was 95%. Two women (1%) had isolated para-aortic metastases. No adverse events occurred during the SLN procedure.
CONCLUSION
With a complete sensitivity to detect pelvic LNMs, the described pelvic SLN algorithm can, in the hands of experienced surgeons, exclude overall nodal involvement in 99% and thereby safely replace a full lymphadenectomy in HREC.
Topics: Adult; Aged; Aged, 80 and over; Algorithms; Endometrial Neoplasms; Female; Humans; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Pelvis; Robotic Surgical Procedures; Sensitivity and Specificity; Sentinel Lymph Node Biopsy; Surgery, Computer-Assisted
PubMed: 31181536
DOI: 10.1016/j.ejca.2019.04.025 -
JAMA Surgery Feb 2021Whether sentinel lymph node biopsy (SLNB) can replace lymphadenectomy for surgical staging in patients with high-grade endometrial cancer (EC) is unclear. (Comparative Study)
Comparative Study
IMPORTANCE
Whether sentinel lymph node biopsy (SLNB) can replace lymphadenectomy for surgical staging in patients with high-grade endometrial cancer (EC) is unclear.
OBJECTIVE
To examine the diagnostic accuracy of, performance characteristics of, and morbidity associated with SLNB using indocyanine green in patients with intermediate- and high-grade EC.
DESIGN, SETTING, AND PARTICIPANTS
In this prospective, multicenter cohort study (Sentinel Lymph Node Biopsy vs Lymphadenectomy for Intermediate- and High-Grade Endometrial Cancer Staging [SENTOR] study), accrual occurred from July 1, 2015, to June 30, 2019, with early stoppage because of prespecified accuracy criteria. The study included patients with clinical stage I grade 2 endometrioid or high-grade EC scheduled to undergo laparoscopic or robotic hysterectomy with an intent to complete staging at 3 designated cancer centers in Toronto, Ontario, Canada.
EXPOSURES
All patients underwent SLNB followed by lymphadenectomy as the reference standard. Patients with grade 2 endometrioid EC underwent pelvic lymphadenectomy (PLND) alone, and patients with high-grade EC underwent PLND and para-aortic lymphadenectomy (PALND).
MAIN OUTCOMES AND MEASURES
The primary outcome was sensitivity of the SLNB algorithm. Secondary outcomes were additional measures of diagnostic accuracy, sentinel lymph node detection rates, and adverse events.
RESULTS
The study enrolled 156 patients (median age, 65.5 years; range, 40-86 years; median body mass index [calculated as weight in kilograms divided by height in meters squared], 27.5; range, 17.6-49.3), including 126 with high-grade EC. All patients underwent SLNB and PLND, and 101 patients (80%) with high-grade EC also underwent PALND. Sentinel lymph node detection rates were 97.4% per patient (95% CI, 93.6%-99.3%), 87.5% per hemipelvis (95% CI, 83.3%-91.0%), and 77.6% bilaterally (95% CI, 70.2%-83.8%). Of 27 patients (17%) with nodal metastases, 26 patients were correctly identified by the SLNB algorithm, yielding a sensitivity of 96% (95% CI, 81%-100%), a false-negative rate of 4% (95% CI, 0%-19%), and a negative predictive value of 99% (95% CI, 96%-100%). Only 1 patient (0.6%) was misclassified by the SLNB algorithm. Seven of 27 patients with node-positive cancer (26%) were identified outside traditional PLND boundaries or required immunohistochemistry for diagnosis.
CONCLUSIONS AND RELEVANCE
In this prospective cohort study, SLNB had acceptable diagnostic accuracy for patients with high-grade EC at increased risk of nodal metastases and improved the detection of node-positive cases compared with lymphadenectomy. The findings suggest that SLNB is a viable option for the surgical staging of EC.
Topics: Adult; Aged; Aged, 80 and over; Endometrial Neoplasms; Female; Humans; Lymph Node Excision; Lymphatic Metastasis; Middle Aged; Neoplasm Grading; Neoplasm Staging; Predictive Value of Tests; Prospective Studies; Sensitivity and Specificity; Sentinel Lymph Node Biopsy
PubMed: 33175109
DOI: 10.1001/jamasurg.2020.5060 -
European Urology Oncology Aug 2021Pelvic lymph node dissection (PLND) is the most reliable procedure for lymph node staging. However, the therapeutic benefit remains unproven; although most radical... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Pelvic lymph node dissection (PLND) is the most reliable procedure for lymph node staging. However, the therapeutic benefit remains unproven; although most radical prostatectomies at academic centers are accompanied by PLND, there is no consensus regarding the optimal anatomical extent of PLND.
OBJECTIVE
To evaluate whether extended PLND results in a lower biochemical recurrence rate.
DESIGN, SETTING, AND PARTICIPANTS
We conducted a single-center randomized trial. Patients, enrolled between October 2011 and March 2017, were scheduled to undergo radical prostatectomy and PLND. Patients were assigned to limited or extended PLND by cluster randomization. Specifically, surgeons were randomized to perform limited or extended PLND for 3-mo periods.
INTERVENTION
Randomization to limited (external iliac nodes) or extended (external iliac, obturator fossa and hypogastric nodes) PLND.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
The primary endpoint was the rate of biochemical recurrence.
RESULTS AND LIMITATIONS
Of 1440 patients included in the final analysis, 700 were randomized to limited PLND and 740 to extended PLND. The median number of nodes retrieved was 12 (interquartile range [IQR] 8-17) for limited PLND and 14 (IQR 10-20) extended PLND; the corresponding rate of positive nodes was 12% and 14% (difference -1.9%, 95% confidence interval [CI] -5.4% to 1.5%; p = 0.3). With median follow-up of 3.1 yr, there was no significant difference in the rate of biochemical recurrence between the groups (hazard ratio 1.04, 95% CI 0.93-1.15; p = 0.5). Rates for grade 2 and 3 complications were similar at 7.3% for limited versus 6.4% for extended PLND; there were no grade 4 or 5 complications.
CONCLUSIONS
Extended PLND did not improve freedom from biochemical recurrence over limited PLND for men with clinically localized prostate cancer. However, there were smaller than expected differences in nodal count and the rate of positive nodes between the two templates. A randomized trial comparing PLND to no node dissection is warranted.
PATIENT SUMMARY
In this clinical trial we did not find a difference in the rate of biochemical recurrence of prostate cancer between limited and extended dissection of lymph nodes in the pelvis. This study is registered on ClinicalTrials.gov as NCT01407263.
Topics: Humans; Lymph Node Excision; Lymph Nodes; Male; Prostate; Prostatectomy; Prostatic Neoplasms
PubMed: 33865797
DOI: 10.1016/j.euo.2021.03.006 -
European Journal of Cancer (Oxford,... May 2021Pelvic lymph node dissection has been the standard of care for patients with early cervical cancer. Sentinel node (SN) mapping is safe and feasible and may increase the... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Pelvic lymph node dissection has been the standard of care for patients with early cervical cancer. Sentinel node (SN) mapping is safe and feasible and may increase the detection of metastatic disease, but benefits of omitting pelvic lymph node dissection in terms of decreased morbidity have not been demonstrated.
MATERIALS AND METHODS
In an open-label study, patients with early cervical carcinoma (FIGO 2009 stage IA2 to IIA1) were randomly assigned to SN resection alone (SN arm) or SN and pelvic lymph node dissection (SN + PLND arm). SN resection was followed by radical surgery of the tumour (radical hysterectomy or radical trachelectomy). The primary end-point was morbidity related to the lymph node dissection; 3-year recurrence-free survival was a secondary end-point.
RESULTS
A total of 206 patients were eligible and randomly assigned to the SN arm (105 patients) or SN + PLND arm (101 patients). Most patients had stage IB1 lesion (87.4%). No false-negative case was observed in SN + PLND arm. Lymphatic morbidity was significantly lower in the SN arm (31.4%) than in the SN + PLND arm (51.5%; p = 0.0046), as was the rate of postoperative neurological symptoms (7.8% vs. 20.6%, p = 0.01, respectively). However, there was no significant difference in the proportion of patients with significant lymphoedema between the two groups. During the 6-month postoperative period, the difference in morbidity decreased over time. The 3-year recurrence-free survival was not significantly different (92.0% in SN arm and 94.4% in SN + PLND arm).
CONCLUSION
SN resection alone is associated with early decreased lymphatic morbidity when compared with SN + PLND in early cervical cancer.
Topics: Adenocarcinoma; Adult; Carcinoma, Squamous Cell; Female; Follow-Up Studies; Humans; Hysterectomy; Lymph Node Excision; Middle Aged; Morbidity; Neoplasm Recurrence, Local; Prognosis; Prospective Studies; Sentinel Lymph Node Biopsy; Survival Rate; Uterine Cervical Neoplasms
PubMed: 33773275
DOI: 10.1016/j.ejca.2021.02.009 -
Journal of Gynecologic Oncology Mar 2021This review aims to introduce preoperative scoring systems to predict lymph node metastasis (LNM) and ongoing clinical trials to investigate the therapeutic role of... (Review)
Review
OBJECTIVES
This review aims to introduce preoperative scoring systems to predict lymph node metastasis (LNM) and ongoing clinical trials to investigate the therapeutic role of lymphadenectomy for endometrial cancer.
METHODS
We summarized previous reports on the preoperative prediction models for LNM and evaluated their validity to omit lymphadenectomy in our recent cohorts. Next, we compared characteristics of two ongoing lymphadenectomy trials (JCOG1412, ECLAT) to examine the survival benefit of lymphadenectomy in endometrial cancer, and described the details of JCOG1412.
RESULTS
Lymphadenectomy has been omitted for 64 endometrial cancer patients who met low-risk criteria to omit lymphadenectomy using our scoring system (LNM score) and no lymphatic failure has been observed. Other two models also produced comparable results. Two randomized phase III trials to evaluate survival benefit of lymphadenectomy are ongoing for endometrial cancer. JCOG1412 compares pelvic lymphadenectomy alone with pelvic and para-aortic lymphadenectomy to evaluate the therapeutic role of para-aortic lymphadenectomy for patients at risk of LNM. For quality assurance of lymphadenectomy, we defined several regulations, including lower limit of the number of resected nodes, and submission of photos of dissected area to evaluate thoroughness of lymphadenectomy in the protocol. The latest monitoring report showed that the quality of lymphadenectomy has been well-controlled in JCOG1412.
CONCLUSION
Our strategy seems reasonable to omit lymphadenectomy and could be generalized in clinical practice. JCOG1412 is a high-quality lymphadenectomy trial in terms of the quality of surgical procedures, which would draw the bona-fide conclusions regarding the therapeutic role of lymphadenectomy for endometrial cancer.
Topics: Endometrial Neoplasms; Female; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Neoplasm Staging; Pelvis
PubMed: 33470067
DOI: 10.3802/jgo.2021.32.e25 -
BMJ Case Reports Jan 2019A 57-year-old man presented with a 6-month history of pelvic fullness. He had no lower urinary tract symptoms or altered bowel habits. On examination, there was a...
A 57-year-old man presented with a 6-month history of pelvic fullness. He had no lower urinary tract symptoms or altered bowel habits. On examination, there was a non-tender pelvic mass which extended from the pubic symphysis to the level of the umbilicus. CT scan of the abdomen demonstrated a 22×11×11 cm cystic mass arising from the pelvis extending into the midline and superiorly to the umbilicus. Other than raised carcinoembryonic antigen of 7.6 ng/mL (<5.0), the remainder of his blood test were unremarkable. Flexible cystoscopy demonstrated a convex deformity of the bladder wall in keeping with the compression and displacement as seen on the CT. The patient underwent an open excision of the cystic structure (urachal remnant), partial cystectomy, partial excision of anterior abdominal wall and pelvic lymphadenectomy. A check cystogram performed 12 days following the initial operation was unremarkable.
Topics: Abdominal Wall; Aftercare; Carcinoembryonic Antigen; Cystadenocarcinoma, Mucinous; Cystectomy; Cystoscopy; Humans; Lymph Node Excision; Male; Middle Aged; Rare Diseases; Tomography, X-Ray Computed; Treatment Outcome; Urachus; Urinary Bladder Neoplasms
PubMed: 30674499
DOI: 10.1136/bcr-2018-228089