Pelvic Lymph Node Dissection In Patients Research Articles

Laparoscopic and Robotic-Assisted Extended Pelvic Lymph Node Dissection for Invasive Bladder Cancer: A Review

Minimally invasive surgical techniques, including laparoscopic and robotic-assisted radical cystectomy (RC), are emerging as the preferred treatment options for invasive bladder cancer. Mounting evidence has demonstrated that laparoscopic and robotic-assisted RC with extended pelvic lymph node dissection (PLND) is a viable alternative for managing invasive bladder cancer. In this review, we summarized recent advances and critically assessed the minimally invasive approaches and risk factors associated with extended PLND in patients undergoing laparoscopic or robotic-assisted RC. The findings indicated that laparoscopic and robotic-assisted PLND, employing either a standard or extended approach, is technically feasible and offers benefits such as minimal invasiveness, superior visualization, reduced blood loss, and expedited recovery. The risk factors involved in the laparoscopic extended PLND are minimal. Clinically, laparoscopic and robotic-assisted extended PLND is significantly advantageous in that it sticks to the principles of open surgery and respects anatomical boundaries. Nevertheless, laparoscopic and robotic-assisted extended PLND is technically challenging and necessitate extended operation time. Furthermore, large-scale, prospective, multicenter trials are warranted to validate the long-term efficacy of laparoscopic and robotic-assisted extended PLND in terms of disease-specific survival.

EDITORIAL COMMENT

The evolution of risk stratifications for prostate cancer reflects advances in anatomic (radiographic), pathologic, and molecular (genomic classifications) understandings. These parameters, combined with traditional “bedside” evaluations of clinical T stage, and PSA values, allow for better sharing of clinical decisions with patients. In this issue of the Gold Journal, investigators MUSIC investigators (Michigan Urological Surgery Improvement Collaborative) sought to improve patient selection criteria for PLND in patients with favorable and unfavorable intermediate risk (F-IR, U-IR) disease by analyzing over 6,800 men who underwent RALP and pelvic lymph node dissection (PLND).

Predictive value of extra-prostatic disease detection by pre-operative PSMA-PET for biochemical recurrence-free survival in patients treated with radical prostatectomy: Follow-up analysis of a multicenter prospective phase 3 imaging trial.

5088 Background: To assess the predictive value of pre-operative PSMA-PET staging for biochemical recurrence (BCR) free-survival (BCR-FS) in patients treated with radical prostatectomy (RP) and pelvic lymph node dissection (PLND) with intermediate-risk (IR) to high-risk (HR) prostate cancer (PCa) included in the prospective trial used for the FDA approval of 68Ga-PSMA-11. Methods: This is a post-hoc follow-up study of the efficacy analysis cohort included in the multicenter prospective phase 3 imaging trial (n = 764; NCT03368547, NCT02611882, NCT02919111) which assessed the diagnostic accuracy of 68Ga-PSMA-11 PET for pelvic nodal metastasis detection prior to RP and PLND in patients with IR and HR PCa. Each PSMA-PET scan was read by three blinded independent readers. Readers assessed the presence of PCa (positive vs negative) by region: prostate bed (T), pelvic lymph nodes (N), extra-pelvic lymph nodes (M1a) bone (M1b) and visceral (M1c). A centralized per-region majority rule was used in case of disagreement. The surgical pathology report was used to assess the presence of pelvic lymph node metastasis by histopathology (pN0 vs pN1). The patients were followed up for biochemical progression after RP by the local investigators using electronic medical records. BCR was defined by a prostate-specific antigen (PSA) level > 0.2 ng/ml after RP or an initiation of PCa specific adjuvant/salvage therapy. Pairwise comparisons using Log-Rank test was performed to evaluate BCR-FS between the pre-operative PSMA scan reads (N0M0 vs. N+ and/or M+) and the histopathology status (pN0 vs. pN1). Results: From December 2015 to December 2019, a total of 764 patients were enrolled in the trial. 277/764 (36%) underwent RP after PSMA-PET. Clinical follow-up was obtained in 240/277 (87%) patients. The median age was 67 years (interquartile range, 61-71 years). The median follow-up time from RP was 21.4 months (IQR: 8.80 - 31.53). One hundred BCR events (41%) were observed, and 98/240 patients underwent salvage therapy or other treatment (40.6%). The BCR-FS was 24.3 (IQR: 7.8 - 48.8) in the whole cohort. 160/240 (66%), 28/240 (11.6%), 39/240 (16%), 13/240 (5.4%) patients were pN0/PSMA- (N0 and M0), pN+/PSMA+ (N+ and/or M+), pN+/PSMA-, and pN0/PSMA+, respectively. BCR-FS was higher in PSMA- than in PSMA+ patients (33 vs 7.3 months; p < 0.0001). BCR-FS was higher in pN0/PSMA- than in patients pN+/PSMA-, pN0/PSMA+ and pN+/PSMA+: 46 months vs 12.3, 11.7, and 3, respectively (p < 0.001). BCR-FS did not significantly differ between pN0/PSMA+ and pN+/PSMA- (11.7 vs 12.3; p = 0.64). Conclusions: PSMA PET staging information is predictive of BCR-FS after RP. Patients with extra-prostatic disease detected by pre-operative PSMA-PET scan have a high risk of biochemical relapse. Clinical trial information: NCT03368547.

Preoperative Predictors of Lymph Node Invasion and Biochemical Recurrence in High-risk Prostate Cancer.

To evaluate the preoperative predictors of pathological lymph node (LN) metastasis and prognostic factors for postoperative biochemical recurrence (BCR) in robot-assisted radical prostatectomy with extended pelvic LN dissection in patients with D'Amico high-risk prostate cancer (PCa). Overall, 107 patients with D'Amico high-risk PCa underwent robot-assisted radical prostatectomy with extended pelvic LN dissection without neoadjuvant or adjuvant therapy. BCR was defined as a prostate-specific antigen (PSA) level ≥0.2 ng/ml. Moreover, BCR-free survival rates were determined using Kaplan-Meier analysis. Logistic regression analysis was used to evaluate preoperative predictors of pathological LN metastasis. Cox regression analysis was used to evaluate the effects of preoperative and pathologic variables on BCR. The median follow-up was 21 months, and the 5-year BCR-free survival rate was 59.8%. The positive LN rate was 21.5%. In multivariate analysis, the percentage of positive cores was a significant preoperative predictor of positive LNs. Patients with >50% positive cores (p=0.004) and PSA density (PSAD) >0.5 ng/ml/cc (p=0.005) had a high risk of having ≥3 positive LNs. In multivariate analysis, PSAD >0.5% was a significant preoperative predictor of BCR. Among the postoperative predictors, the number of positive LNs was significantly associated with BCR. Patients with ≥3 positive LNs (n=7) had significantly lower BCR-free survival rates than patients with one or two positive LNs (n=16) (p<0.001). Patients with >50% positive cores and PSAD >0.5 ng/ml/cc had a risk for a high number of positive LNs (≥3) that was strongly associated with shorter BCR-free survival (p<0.001). The percentage of positive cores may be useful as a preoperative predictor of pathological LN metastasis in patients with high-risk PCa. Patients with >50% positive cores and PSAD >0.5 ng/ml/cc were found to have a high risk for ≥3 positive LNs and shorter BCR-free survival.

Dissecting patterns of care in patients with variant histology of bladder cancer and lymph node invasion

Objectives Lymph node invasion (LNI) is related to long-term survival in patients with muscle-invasive bladder cancer. However, in the case of variant histology (VH), data on pelvic lymph node dissection (PLND) and LNI are sparse. We described the pattern of care of PLND in patients with VHs of bladder cancer, exploring predictors of LNI. Methods Using the 2001–2016 SEER registry, 20 767 bladder cancer patients who underwent PLND were identified. Included histological variants were pure urothelial carcinoma (UC), micropapillary UC, sarcomatoid UC, lymphoepithelioma-like UC, adenocarcinoma, sarcoma, giant and spindle cell carcinoma, squamous cell carcinoma (SCC), and neuroendocrine tumor. Uni- and multivariable logistic regression analyses tested for LNI predictors. Cox regression was used to test for predictors of overall mortality (OM) among both LNI positive and LNI negative patients. Results Overall, 2464 (11.9%) harbored a VH. On multivariate analysis, only micropapillary UC was associated with higher risk (OR = 3.39) of LNI. This association was maintained when only the subset of patients treated without perioperative chemotherapy were analyzed (OR = 3.30). Similarly, higher T stage (T2 stage OR = 2.24; T3–4 stage OR = 9.44) and the use of chemotherapy (OR = 2.29) were associated with a higher risk of LNI. Among patients with LNI (5299, 25.5%), SCC (HR = 1.87), T3–4 stage (HR = 1.94), age at diagnosis (HR = 1.01) and geographic region (south) (HR = 1.22) were predictors of higher risk of OM. Conversely, chemotherapy (HR = 0.69) and number of removed LN (HR = −0.99) were associated with lower risk of OM. Finally, in a subgroup of patients without LNI, sarcomatoid UC (HR = 1.58) and giant and spindle cell carcinoma (HR = 1.83) were the only VH predictors of OM. Conclusions We described different patterns of care in patients with VHs of bladder cancer. Micropapillary UC was an independent risk factor for LNI. Among patients harboring LNI, those with SCC VH had higher OM compared to pure UC. Conversely, sarcomatoid UC and giant and spindle cell carcinoma were predictors of OM in patients without nodal involvement.

A narrative review of pelvic lymph node dissection in prostate cancer.

Pelvic lymph node dissection (PLND) is an important component in the staging and prognostication of prostate cancer. We performed a narrative review to assess the literature surrounding PLND: (I) the current guideline recommendations and contemporary utilization, (II) the calculation of patient-specific risk to perform PLND using available nomograms, (III) to review the extent of dissection, and its associated outcomes and complications. Due to the improved lymph node yield, better staging, and theoretical improvement in the control of micro-metastatic disease, guidelines have supported the use of (extended-) PLND in patients deemed to be at intermediate or high risk of lymph node involvement (often at a threshold of 5% on modern risk nomograms). However, in practice, real-world utilization of PLND varies considerably due to multiple reasons. Conflicting evidence persists with no clear oncological benefit to PLND, and a small, but important, risk of morbidity. Complications are rare, but include lymphoceles; thromboembolic events; and more rarely, obturator nerve, vascular, and ureteric injury. Furthermore, changing disease incidence and stage migration in the context of earlier detection overall have led to a decreased risk of nodal disease. The trade-offs between the benefits, harms, and risk tolerance/threshold must be carefully considered between each patient and their clinician.

Pelvic Lymph Node Dissection During Cystectomy for Patients With Bladder Carcinoma With Variant Histology: Does Histologic Type Matter?

PurposeAdding pelvic lymph node dissection (PLND) to cystectomy offers significant survival benefit. However, it remains unclear whether this benefit persists in all histologic types. The aim of the study was to examine the impact of PLND on overall survival (OS) after cystectomy in bladder carcinoma patients with histological variants.MethodsWithin the Surveillance, Epidemiology and End Results database, we identified 16,880 bladder carcinoma patients receiving cystectomy between 2004 and 2015. Patients were stratified according to the following histologic types: transitional cell carcinoma, squamous cell carcinoma, adenocarcinoma, small cell carcinoma, neuroendocrine carcinoma, signet ring cell carcinoma, pseudosarcomatous carcinoma, and other histology. Cox regression models were used to evaluate the effect of PLND on OS stratified by histologic type.ResultsHistologic types were significantly associated with the presence of lymph node metastasis in patients with bladder carcinoma (P < 0.001). In multivariable Cox regression analyses, PLND compared with non-PLND was associated with OS benefit in patients with transitional cell carcinoma (hazard ratio [HR], 0.595; 95% confidence interval [95% CI], 0.557–0.634 [P < 0.001]), squamous cell carcinoma (HR, 0.646; 95% CI, 0.494–0.846 [P = 0.002]), and signet ring cell carcinoma (HR, 0.233; 95% CI, 0.107–0.504 [P < 0.001]), whereas no significant differences in OS were observed in other histological subsets.DiscussionOur analyses revealed a significant OS benefit from PLND in patients with transitional cell carcinoma, squamous cell carcinoma, and signet ring cell carcinoma. However, a survival benefit of PLND in patients with other histologic types was not demonstrated.

Determinants of adequate lymphnode dissection following neoadjuvant chemotherapy in patients with urothelial muscle-invasive bladder cancer: results from the National Cancer Database.

Recent literature has separately identified multiple determinants of the use of neoadjuvant chemotherapy (NAC) and adherence to pelvic lymphnode dissection (PLND) guidelines in the management of non-metastatic bladder cancer. However, such NAC/PLND analyses tend not to account for the other modality, despite the fact that NAC may impact the extent of dissectible lymph nodes. We aimed to determine the predictors of adequate PLND in patients with non-metastatic urothelial muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC) following receipt of NAC. We queried the National Cancer Database to identify patients from 2006-2015 with cT2-cT4a/N0M0 urothelial MIBC who underwent RC and were pre-treated with NAC. Multivariate logistic regression analysis was used to identify independent predictors of undergoing an adequate PLND (defined as > 8 nodes). A total of 1518 patients met the criteria for inclusion (74.4% underwent adequate PLND). Adequate PLND was associated with treatment at an academic research facility (OR 2.762 [95% CI 2.119-3.599], p < 0.001). The likelihood of adequate PLND was significantly decreased in patients of older age (0.607 [0.441-0.835], p = 0.002 for age 70-79years; 0.459 [0.245-0.860], p = 0.015 for age ≥ 80years), a Charlson-Deyo score of 1 (0.722 [0.537-0.971], p = 0.031), and those who were uninsured (0.530 [0.292-0.964], p = 0.038). Established predictors of PLND may not necessarily be generalizable to all patients undergoing treatment for bladder cancer. The interplay between PLND and NAC merits further study, particularly in view of recent literature calling into question the survival benefit of PLND in patients pre-treated with NAC.

Increased Frequency of Mesorectal and Perirectal LN Involvement in T4 Prostate Cancers

Patients with prostate cancer presenting with advanced T stage, mainly T4, might have a unique pattern of nodal failure and disease involvement that is not typically covered when local therapy is offered. We attempted to identify common sites of nodal disease presentation and failure for patients presenting with cT4 prostate cancer. All patients with treatment-naïve cT4 prostate cancer were retrospectively identified. All patients were required to have a confirmed diagnosis reviewed by our genitourinary pathologist and completed baseline staging. Lymph node (LN) involvement and location at diagnosis were reviewed by a genitourinary radiologist. All patients' follow-up scans were also reviewed; based on LN size, imaging characteristics, and progression/regression characteristics on systemic therapy, the locations of sites of LN failure were recorded. For patients who underwent surgery, any pathologically involved LNs and their anatomic locations were recorded. A total of 103 patients met these criteria, with a median follow-up of 8 years (range, 0.5-14 years). Rectal involvement by the primary disease was associated with a higher risk of perirectal and mesorectal LN involvement (45%) relative to no rectal involvement (26%) (P < .05). These echelons are typically not covered with conventional pelvic external beam radiation therapy and are not routinely part of pelvic LN dissection in patients treated surgically. Conversely, bladder or pelvic side wall invasion did not correlate with increased frequency of involvement of perirectal/mesorectal LNs (P > .05). When offering local therapy, target modification to include the perirectal and mesorectal LNs should be considered for patients presenting with T4 prostate cancer with rectal involvement.

Surgical Safety of Radical Cystectomy and Pelvic Lymph Node Dissection Following Neoadjuvant Pembrolizumab in Patients with Bladder Cancer: Prospective Assessment of Perioperative Outcomes from the PURE-01 Trial

No data are available on the surgical safety of radical cystectomy (RC) and pelvic lymph node dissection (PLND) after the administration of checkpoint inhibitors. We aimed at reporting the first prospective rigorous assessment of perioperative outcomes after RC and extended PLND following neoadjuvant pembrolizumab in a contemporary cohort of patients with muscle-invasive bladder cancer (MIBC) enrolled in the PURE-01 trial. From February 2017 to June 2019, a total of 68 consecutive patients who received three courses of 200 mg pembrolizumab intravenously every 3 wk and were subsequently treated with either open or robot-assisted RC and PLND at a single high-volume tertiary referral center were identified. All men had prospectively collected data about intra- and postoperative outcomes. Postoperative complications were graded according to the Clavien-Dindo system. Perioperative data were prospectively and systematically collected during patient interviews at 90 d after surgery according to the European Association of Urology (EAU) Guidelines Panel recommendations on reporting and grading complications. Overall, 52 (77%) versus 16 (23%) patients underwent robot-assisted versus open RC, and 31 patients (46%) received an orthotopic neobladder. Median blood loss and length of stay were 150 ml and 12 d, respectively. Overall, 52 (77%), 47 (69%), and 22 (32%) patients experienced any-grade complications, grade ≥2 complications, and readmission at 90 d, respectively. High-grade complications (defined as Clavien-Dindo ≥3a) were observed in 23 patients (34%). The most frequent complications were fever (n = 35, 52%) and ileus (n = 21, 31%). None of the patients experienced perioperative mortality at 90 d. Our data represent the first prospective evidence supporting the surgical safety of RC and PLND in patients with N0M0 MIBC who received neoadjuvant immunotherapy with pembrolizumab. Patient summaryThe current study represents the first prospective evidence supporting the surgical safety of radical cystectomy and pelvic lymph node dissection in patients with nonmetastatic bladder cancer who received neoadjuvant immunotherapy with pembrolizumab.

Extended versus standard lymph node dissection for urothelial carcinoma of the bladder in patients undergoing radical cystectomy.

In the treatment of urothelial carcinoma of the bladder, we are currently uncertain of the benefits and harms of standard pelvic lymph node dissection (PLND) compared to extended PLND. To assess the effects of extended versus standard PLND in patients undergoing cystectomy to treat muscle-invasive (cT2 and cT3) and treatment-refractory, non-muscle-invasive (cT1 with or without carcinoma in situ) urothelial carcinoma of the bladder. We performed a comprehensive literature search using multiple databases (PubMed, Embase, Cochrane Controlled Trials, Web of Science, and LILACS), trial registries, and conference proceedings published up to April 29, 2019, with no restrictions on the language or status of publication. We included randomized controlled trials in which participants underwent radical cystectomy (RC) for muscle-invasive or therapy-refractory non-muscle-invasive urothelial carcinoma of the bladder with either an extended PLND with a superior extent reaching as far cranially as the inferior mesenteric vein, or a standard PLND with a superior extent of the bifurcation of the internal and external iliac artery, with otherwise the same anatomical boundaries. Two review authors independently assessed the included studies and extracted data from them for the primary outcomes: time to death from any cause, time to death from bladder cancer and Clavien-Dindo classification of surgical complications grade III-V, and the secondary outcomes: time to recurrence, Clavien-Dindo I-II complications and disease-specific quality of life.We performed statistical analyses using a random-effects model and rated the certainty of evidence according to the GRADE approach. The search identified one multicenter trial based in Germany that enrolled 401 participants with histologically confirmed T1 grade 3 or muscle-invasive urothelial carcinoma. The median age was 67 years (range: 59 to 74) and the majority of participants were male (78.3%). No participant received neoadjuvant chemotherapy; a small subset received adjuvant chemotherapy (14.5%).Primary outcomesOur results indicate that extended PLND may reduce the risk of death from any cause over time as compared to standard PLND, but the confidence interval includes the possibility of no effect (hazard ratio [HR]: 0.78, 95% confidence interval [CI]: 0.57 to 1.07, 401 participants, low-certainty evidence). After five years of follow-up, this may result in 83 fewer deaths (95% CI: 174 fewer to 24 more overall deaths) per 1000 participants: 420 deaths for extended PLND compared to 503 deaths per 1000 for standard PLND. We downgraded the certainty of evidence by two levels due to study limitations and imprecision.Our results indicate that extended PLND may reduce the risk of death from bladder cancer over time as compared to standard PLND but, again, the confidence interval includes the possibility of no effect (HR: 0.70, 95% CI: 0.45 to 1.07, participants = 401, low-certainty evidence). After five years of follow-up, this corresponds to 91 fewer deaths per 1000 participants (95% CI: 176 fewer to 19 more bladder cancer deaths): 264 deaths for extended PLND compared to 355 deaths per 1000 for standard PLND. We downgraded the certainty of evidence by two levels due to study limitations and imprecision.Based on follow-up of up to 30 days, we are uncertain whether extended PLND leads to more grade III-V complications as compared to standard PLND, because of study limitations and imprecision (risk ratio [RR]: 1.13, 95% CI: 0.84 to 1.52, participants = 401, very low-certainty evidence).Secondary outcomesWe are uncertain whether extended PLND reduces the risk of recurrence over time as compared to standard PLND, because of study limitations and imprecision (HR: 0.84, 95% CI: 0.58 to 1.22, participants = 401, very low-certainty evidence).Based on follow-up of up to 30 days, we are uncertain whether extended PLND leads to similar grade I-II complications as compared to standard PLND because of study limitations and imprecision (RR: 0.94, 95% CI: 0.74 to 1.19, participants = 401, very low-certainty evidence).We found no trials that reported on disease-specific quality of life. Results from a single trial indicate that extended PLND in patients undergoing radical cystectomy for invasive urothelial carcinoma of the bladder may reduce death from any cause and death from bladder cancer over time; however, the results include the possibility of no effect. We are uncertain whether the risk of serious complications up to 30 days may be increased. We are also uncertain as to whether the risk of recurrence over time or the risk of minor complications up to 30 days changes. We were unable to conduct any of the preplanned subgroup analyses, in particular, analyses based on extended lymph node dissection templates, clinical tumor stage, and use of neoadjuvant chemotherapy that may be important effect modifiers. Important additional data is expected from a larger, ongoing trial that will also consider the role of neoadjuvant chemotherapy. Inclusion of this trial in the meta-analysis may help address the issue of imprecision which was a common reason for downgrading the certainty of the evidence.

Abstract 3920: Tumor volume as a predictor of lymph node metastases in prostate cancer

Abstract Introduction: Pelvic lymph node dissection (PLND) is recommended during radical prostatectomy (RP) in patients with high risk prostate cancer (PCa). Guidelines recommend extended PLND in patients who have &amp;gt;5% probability of lymph node involvement, calculated from pre-operative parameters. PLND increases procedure time and potential morbidity to patients. Tumour size has been reported to be predictive of biochemical recurrence after RP. We analysed the utility of several parameters including tumour size in predicting lymph node metastases in order to further refine the population who require PLND during RP. Materials &amp; Methods: We maintained a prospective database of Robotic Assisted Radical Prostatectomy (RARP) from July 2012 to August 2016 consisting of a cohort of 531 patients. Patients with &amp;gt;5% calculated probability of lymph node metastasis had PLND during RARP. We performed multiple linear regression using age, PSA, D’Amico risk score, ISUP prognostic group, clinical T-stage, radiological T-stage, tumour volume, tumour volume relative to prostate size (relative tumour volume), and number of nodes excised during PLND to determine if any of these parameters could predict the presence of lymph node metastases. Results: Of the cohort of 531 patients, 154 had PLND during RARP. Of the PLND cohort, 15 (10%) had pN1 disease. Tumour volume (r2 0.044, p= 0.0098), relative tumour volume (r2 0.033, p=0.026) and number of lymph nodes excised (r2 0.046, p=0.0075) were independent predictors of pN1 disease. D’Amico risk score (r2 0.019, p=0.089) approached but did not reach statistical significance. Patients with pN1 disease all had primary tumours ≥6cc. Conclusions: In our cohort of PLND patients, tumour volume was an independent risk factor for pN1 disease. With the increasing availability of multi-parametric MRI, tumour volume can be measured pre-operatively as an adjunct to PIRADS scoring. The role of tumour volume and relative tumour volume in predicting lymph node metastasis in conjunction with other pre-operative parameters requires further investigation. The use of tumour volume in determining the need for PLND in patients undergoing RP may help to further refine the population at highest risk for pN1 disease and avoid the additional morbidity of PLND in those at low risk. In addition, our findings support the recommendation of performing an extended PLND to maximise regional lymph node clearance. Citation Format: Chidi N. Molokwu, Keith Yuen, Sanjay Addla, Rajindra Singh, Rohit Chahal. Tumor volume as a predictor of lymph node metastases in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3920. doi:10.1158/1538-7445.AM2017-3920

Near-infrared Intraoperative Molecular Imaging Can Identify Metastatic Lymph Nodes in Prostate Cancer

To propose a novel method to perform indocyanine green (ICG) based near-infrared (NIR) fluorescence imaging during pelvic lymph node dissection (PLND) for prostate cancer patients with lymph node metastasis (LNM). A prostate cancer cell line PC3 was used to establish xenograft model in NOD/SCID mice. After tumor growth, the mice were injected with ICG through the tail vein. Xenografts and surrounding tissues were imaged with NIR camera 24 hours after intravenous ICG, and tumor-to-background ratios were calculated. We then performed a pilot human study to evaluate the role of NIR imaging in robotic PLND after systemic ICG in 4 patients with prostate cancer and preoperative lymphadenopathy. ICG localized to PC3 xenografts in the mice and all xenografts were highly fluorescent compared with surrounding tissues, with a median tumor-to-background ratio of 2.85 (interquartile range = 2.64-3.90). In the human study, intraoperative in vivo NIR imaging identified 3 of the 4 preoperative lymphadenopathies as fluorescence-positive, and back table ex vivo NIR imaging identified all 4 lymphadenopathies as fluorescence-positive. All the lymphadenopathies were found to be LNMs by pathologic examination. Two of the four cases had additional LNMs, all of which were fluorescence-positive with intraoperative in vivo NIR imaging. Intravenously administered ICG accumulates in prostate cancers in both a murine model and human patients. NIR fluorescence based on intravenous ICG may serve as a useful tool to facilitate the identification of positive nodes during PLND in patients with higher risk of LNMs.

Robotic-assisted pelvic lymph node dissection for prostate cancer: frequency of nodal metastases and oncological outcomes.

Limited data are available regarding the oncologic efficacy of pelvic lymph node dissection (PLND) performed during robotic-assisted laparoscopic prostatectomy (RALP) for prostate cancer. We aimed to determine the frequency of pelvic lymph node metastasis and oncological outcomes following RALP with PLND in patients who did not receive adjuvant androgen deprivation therapy (ADT). We retrospectively reviewed the records of 1740 consecutive patients who underwent RALP and extended PLND. The primary endpoint was biochemical recurrence (BCR). The estimated BCR probability was obtained using the Kaplan-Meier method. Cox proportional hazard regression models were used to assess for predictors of BCR. One hundred and eight patients (6 %) with positive LNs were identified. The median number of LNs removed was 17 (IQR 11-24), and median follow-up was 26 months (IQR 14-43). Ninety-one (84 %) patients did not receive adjuvant ADT of whom 60 % had BCR with a median time to recurrence of 8 months. The 1- and 3-year BCR-free probability was 42 and 28 %, respectively. Patients with ≤2 LN+ had significantly better biochemical-free estimated probability compared to those with >2 LN+ (p = 0.002). The total number of LN+ (HR = 1.1; 95 % CI 1.01-1.2, p = 0.04) and Gleason 8-10 (HR = 1.96; 95 % CI 1.1-3.4, p = 0.02) were predictors of BCR on multivariate analysis. Among men with positive lymph nodes at time of robotic prostatectomy, those with two or fewer positive nodes and Gleason <8 exhibited favorable biochemical-free survival without adjuvant therapy.

MP37-20 INDIVIDUAL SURGEON COMMITMENT TO PELVIC LYMPH NODE DISSECTION RATHER THAN SURGICAL VOLUME IS A MAJOR DETERMINANT OF THE EXTENT OF NODAL DISSECTION DURING ROBOT-ASSISTED RADICAL PROSTATECTOMY

INTRODUCTION AND OBJECTIVES: Previous studies showed substantial variability in the number of lymph nodes removed during pelvic lymph node dissection (PLND) in prostate cancer (PCa) patients treated with robot-assisted radical prostatectomy (RARP). We aimed at evaluating the impact of the surgeon experience and individual surgeon commitment on the number of nodes removed during PLND in patients treated with RARP METHODS: Overall, 1173 patients with PCa treated with RARP between 2006 and 2013 by four experienced surgeons at a single center were identified. Surgical volume was coded as the number of robotic cases done by the surgeon before the index patient’s operation. The surgeon ID was classified as follows: surgeon 1, 2, 3, and 4. The Kruskal-Wallis test was used to compare median number of nodes removed according to the surgeon ID. Multivariate linear regression analyses (MVA) were fitted to identify predictors of the extent of PLND (namely, the number of lymph nodes removed). Covariates consisted of clinical stage, biopsy Gleason score (GS), preoperative PSA, surgeon ID, and surgical volume. We repeated our analyses after stratifying patients according to NCCN risk group (lowvs. intermediate/high-risk) RESULTS: Mean age was 62.5 years (median: 63). Mean surgical volume was 194 (median: 190). Overall, 825 patients (70.3%) received PLND. The median number of lymph node removed was 8 (mean: 10). The median number of nodes removed significantly varied according to the surgeon (from 6 to 12 for surgeon 1 and surgeon 4, respectively; p<0.001). In MVA, surgical volume was not associated with the number of nodes removed, after accounting for confounders (p1⁄40.2). On the other hand, the performance of PLND by surgeon 4 was significantly associated with the removal of a higher number of lymph nodes compared to surgeon 1 (P<0.001). Other predictors of a higher number of nodes removed were clinical stage and biopsy GS (all P 0.01). These results were confirmed after stratifying patients in lowvs. intermediate/high-risk disease, where the performance of RARP by surgeon 4, but not the surgical volume, was a significant predictor of the removal of a higher number of lymph nodes (all p<0.001). Of note, in intermediate/high-risk patients, clinical stage and biopsy GS represented also independent predictors of the number of nodes removed (all P 0.01) CONCLUSIONS: In patients treated with RARP undergoing PLND, individual surgeon commitment rather then the surgical experience has a major impact on extent of nodal dissection

Indication for and Extension of Pelvic Lymph Node Dissection During Robot-assisted Radical Prostatectomy: An Analysis of Five European Institutions

BackgroundSeveral reports have shown that patients who undergo minimally invasive radical prostatectomy have a lower chance of undergoing pelvic lymph node dissection (PLND), irrespective of the disease characteristics. ObjectiveWe evaluated the rate and extension of PLND in patients who underwent robot-assisted radical prostatectomy (RARP). We tested the adherence of the indication for PLND to the European Association of Urology (EAU) guidelines. Design, setting, and participantsOur study was a multi-institutional retrospective analysis of prospectively collected data on 2985 consecutive patients who underwent RARP at five high-volume European institutions. Patients were stratified according to preoperative cancer risk group. InterventionRARP. Outcome measurements and statistical analysisThe rate and extent of PLND across different institutions were analyzed. Univariable and multivariable logistic regression models evaluated the association between preoperative variables and the probability of receiving PLND, as well as the presence of lymph node invasion (LNI). Finally, the probability of LNI was calculated for each patient, and the indication for PLND was compared with the EAU guidelines’ indications. Results and limitationsA lymph node dissection was performed in 1777 patients (59.7%; 34.5% of low-risk patients, 64.9% of intermediate-risk patients, and 91.2% of high-risk patients). These rates were different across institutions: 5.0–41.4% in low-risk patients (p<0.001), 31.3–81.4% in intermediate-risk patients (p<0.001), and 84.6–96.4% in high-risk patients (p=0.06). The mean and median number of nodes removed was 10.8, and 122 patients (4.1%) had nodal metastases. At multivariable analysis, the institution represented an independent predictor of PLND (p<0.001). Of patients with current indication for PLND (EAU guidelines), 77.8% actually received the procedure. Limitations were the retrospective study design with different pathologic assessment and lack of follow-up data. ConclusionsPLND is performed in a high proportion of patients undergoing RARP in high-volume centers in Europe for whom the procedure is indicated by the EAU guidelines, but significant differences exist among institutions. An effort toward a more rigorous standardization of PLND is advocated. Patient summaryIn this paper, we investigated the indication for and extension of pelvic lymph node dissection (PLND) in different institutions in Europe. Despite PLND being widely performed, significant variations with regard to PLND do exist among different institutions. Therefore, a thrust toward more rigorous attention to PLND is advocated.

Current status of pelvic lymph node dissection in prostate cancer.

Pelvic lymph node dissection (PLND) is presently considered the gold standard for the detection of lymph node invasion in prostate cancer (PCa) patients. Controversy exists over the adequate extent of PLND for patients at different stages of PCa and over the therapeutic value of the procedure. The most recent consensus advocates extended PLND (ePLND) in a patient with Gleason score ≥7 and serum prostate-specific antigen>10 ng/ml who is undergoing radical prostatectomy. Critics claim more aggressive dissection is associated with an increase in complications, hospitalization time, and cost. The present review examines the debate of limited versus ePLND, and discusses the potential value of the latter for patients with PCa. Furthermore, it examines the utility of robotic-assisted surgery in performing PLNDs with both comparable oncological outcomes and comparable complication rates. The literature has reported promising results that support both diagnostic and therapeutic benefits of ePLND. However, prospective, multi-center, long-term studies are necessary to alleviate criticism of the increased risk of complications and costs of performing PLND.

Extended Pelvic Lymph Node Dissection in Patients Undergoing Robot-Assisted Laparoscopic Radical Cystectomy

Introduction: Extended pelvic lymph node dissection (PLND) during radical cystectomy may be important not only for improved staging, but also for a survival benefit. To assess the utility of robotic surgery in lymph node dissection, we evaluated the feasibility, safety, and efficacy of extended PLND in patients undergoing robot-assisted laparoscopic radical cystectomy (RARC) for urothelial carcinoma of the bladder. Materials and Methods: Thirty-six patients with invasive urothelial carcinoma of the bladder underwent extended PLND during RARC by a single surgeon between March 2011 and December 2012. Preoperative, intraoperative, and postoperative parameters were recorded and analyzed. Surgical Technique: Extended PLND was performed following radical cystectomy incorporating a template dissection using as boundaries, the node of Cloquet distally, genitofemoral nerve anteriorly, iliacus muscle laterally, hypogastric vessels inferiorly, and aortic bifurcation proximally, including the presacral region. In select cases, when suspicious nodes at the common iliac artery were encountered, para-aortic and precaval lymph nodes to the level of the inferior mesenteric artery were incorporated. Results: The median age at surgery was 70 years (interquartile range [IQR]: 63–77), with median body mass index at 25 kg/m2 (IQR: 23–27). The median estimated blood loss was 200 mL (IQR: 100–400) and the transfusion rate was 11% for the entire surgery. The median length of hospital stay was 9 days (IQR: 7–13). No complications attributed to the node dissection occurred, including obturator nerve injuries or clinically significant lymphoceles. A median number of 31 nodes (IQR: 24–40) were harvested in 36 patients. Of these patients, there were 24 (67%) who were node-negative and 12 (33%) who were node-positive. There were 17 (47%) patients with T3/T4 pathologic stage, of which, nine were node-positive. The node-positive rates were higher in T3/T4 stage patients (p = 0.018). At a median follow-up time of 16 months (IQR: 11–21), 25 patients were alive and disease free, four were alive with metastasis, four died of metastatic disease, and three died of unrelated causes. All eight cases of recurrence had positive lymph nodes. Conclusions: Extended PLND during RARC is technically feasible and safe. As a surrogate to long-term survival, comparable lymph node yields may be achieved with a thorough extended lymph node dissection in patients undergoing RARC. No competing financial interests exist. Runtime of video: 8 mins 40 secs

Does Pelvic Lymph Node Dissection Improve the Biochemical Relapse-Free Survival in Low-Risk Prostate Cancer Patients Treated by Laparoscopic Radical Prostatectomy?

The roles and criteria for pelvic lymph node dissection (PLND) are not fully evaluated in patients with low-risk prostate cancer who are treated by laparoscopic radical prostatectomy (LRP). In this study, the outcome of PLND was assessed in terms of the biochemical relapse-free survival rates of low-risk prostate cancer patients who had undergone LRP. Included were 286 consecutive patients who were treated with LRP without previous endocrine therapy between 2002 and 2006 at our institution. Failure rates for LRP were compared in 139 patients with low-risk prostate cancer between those who underwent PLND (n=85) and those who did not (n=54). Biochemical relapse-free survival for each group was estimated by Kaplan-Meier analysis. The mean number of retrieved lymph nodes was 5.4 ± 0.4 (range 2-22). The 5- and 7-year biochemical relapse-free survival rates were 90.1% and 88.3% in patients with PLND, and 82.4% and 82.4% in those without PLND (P=0.278), respectively (median follow-up 69.4 mos). None of the 85 patients undergoing PLND had positive lymph nodes. Only one patient had symptomatic lymphocele, and he was treated as an inpatient. The average time needed for PLND was 16 minutes, which corresponded to 7% of the entire operative time. These results indicate that the dissection of pelvic lymph nodes is not related to biochemical relapse-free survival. The omission of PLND in patients with low-risk prostate cancer not only does not adversely affect biochemical relapse-free survival, but might decrease the incidence of complication and operative time of LRP.

Complications of Pelvic Lymph Node Dissection for Prostate Cancer

Pelvic lymph node dissection (PLND) represents the standard for detection of occult pelvic nodal metastases from prostate cancer, and may be performed separately from or at the time of radical prostatectomy. In addition to its potential for diagnostic staging, a PLND may be therapeutic in some patients. However, considerable debate centers on the appropriate candidates for the procedure, the extent and proper boundaries of dissection, optimal surgical approach, and absolute oncologic benefit. Several series suggest that there likely is limited benefit of PLND in low-risk patients and that PLND can be safely omitted in a high percentage of men undergoing contemporary radical prostatectomy. Furthermore, the value of PLND in patients with intermediate- and high-risk disease must be balanced against the potential morbidity of the procedure. In the setting of this debate, concern over morbidity directly attributable to this procedure is of paramount importance. This review focuses on the complications associated with PLND, including lymphocele, thromboembolic events, ureteral injury, nerve injury, vascular injury, and lymphedema.