Lymph node dissection (LND) represents a key topic in the management of patients with uro-oncological diseases. In prostate, bladder, kidney, testis and penis cancer, the role of LND has been changing over the years due to the increasing amount of clinical, basic research and translational data published. This Research Topic aims to gather the recent data in terms of pathophysiology, anatomy and clinical impact of LND in different urological settings.

San Raffaele Hospital (IRCCS)

Rhode Island Hospital

Luzerner Kantonsspital

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Frontiers in Surgery

Genitourinary Surgery

Lymph Node Dissection in Uro-Oncology

Background: Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) plays a crucial role in treatment of metastatic non-seminomatous germ cell cancer.Objective: To evaluate the functional outcome regarding the preservation of ejaculatory function comparing a bilateral vs. unilateral template resection in PC-RPLND patients. In addition, oncological safety and perioperative complications of the unilateral template resection was compared to the full bilateral one.Design/Setting/Participants: Between 2003 and 2018, 504 RPLNDs have been performed in 434 patients. The database of consecutive patients was queried to identify 171 patients with PC-RPLND after 1st line chemotherapy for a non-seminoma with or without bilateral template resection. Re-Do's, late relapse, salvage patients, and thoraco-abdominal approaches were excluded. Indication for a template resection was a unilateral residual mass mainly <5 cm as published (<xref ref-type="bibr" rid="B1">1</xref>).Outcome, Measurement, and Statistical Analysis: Descriptive statistics were used to report preoperative features, postoperative outcomes and patterns of recurrence, on the overall population and after stratification for the type of resection (bilateral vs. unilateral). Kaplan-Meier analyses were used to describe recurrence- and cancer-specific mortality-free survival rates at different time points.Results and Limitations: Overall, 90 and 81 patients underwent unilateral and bilateral radical resection, respectively. Median size of residual mass was 7 cm for bilateral and 4 cm for unilateral template resection. Clinical stage II and III were present in 31 and 69% of patients, respectively. Median follow-up was 14.5 months (IQR 3.3–37.6). The 1- and 2-year recurrence-free survival rates were 91 and 91%, and 77 and 72% for patients treated with unilateral template and bilateral resection, respectively (p = 0.0078). Median time to recurrence was 9.5 and 9 months in template and bilateral resection group, respectively.Adjunctive procedures were performed in 56 patients (33%) and were significantly more frequent in the bilateral resection group (43 vs. 23%, p = 0.006). The overall high-grade complication rate (Clavien-Dindo ≥ III) was 6, 3, and 9% in unilateral template and bilateral resection group, respectively (p = 0.6). The rate of preservation of antegrade ejaculation was significantly higher in the unilateral group.Conclusions: Antegrade ejaculation in patients undergoing unilateral template resection with a residual mass <5 cm can be preserved at a much higher rate. Moreover, this surgical procedure is oncologically safe in terms of mid-term recurrence and CSM-free survival rates. This data undermines the growing evidence of limited PC-RPLND being justifiable in strictly unilateral residual mass <5 cm. This data has to be confirmed with a longer follow-up regarding in-field and retroperitoneal recurrences.

Background: Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) plays a crucial role in treatment of metastatic non-seminomatous germ cell cancer.Objective: To evaluate the functional outcome regarding the preservation of ejaculatory function comparing a bilateral vs. unilateral template resection in PC-RPLND patients. In addition, oncological safety and perioperative complications of the unilateral template resection was compared to the full bilateral one.Design/Setting/Participants: Between 2003 and 2018, 504 RPLNDs have been performed in 434 patients. The database of consecutive patients was queried to identify 171 patients with PC-RPLND after 1st line chemotherapy for a non-seminoma with or without bilateral template resection. Re-Do's, late relapse, salvage patients, and thoraco-abdominal approaches were excluded. Indication for a template resection was a unilateral residual mass mainly &lt;5 cm as published (<a href="fsurg-05-00080-HTML.html#B1" style="color:grey;">1</a>).Outcome, Measurement, and Statistical Analysis: Descriptive statistics were used to report preoperative features, postoperative outcomes and patterns of recurrence, on the overall population and after stratification for the type of resection (bilateral vs. unilateral). Kaplan-Meier analyses were used to describe recurrence- and cancer-specific mortality-free survival rates at different time points.Results and Limitations: Overall, 90 and 81 patients underwent unilateral and bilateral radical resection, respectively. Median size of residual mass was 7 cm for bilateral and 4 cm for unilateral template resection. Clinical stage II and III were present in 31 and 69% of patients, respectively. Median follow-up was 14.5 months (IQR 3.3–37.6). The 1- and 2-year recurrence-free survival rates were 91 and 91%, and 77 and 72% for patients treated with unilateral template and bilateral resection, respectively (p = 0.0078). Median time to recurrence was 9.5 and 9 months in template and bilateral resection group, respectively.Adjunctive procedures were performed in 56 patients (33%) and were significantly more frequent in the bilateral resection group (43 vs. 23%, p = 0.006). The overall high-grade complication rate (Clavien-Dindo ≥ III) was 6, 3, and 9% in unilateral template and bilateral resection group, respectively (p = 0.6). The rate of preservation of antegrade ejaculation was significantly higher in the unilateral group.Conclusions: Antegrade ejaculation in patients undergoing unilateral template resection with a residual mass &lt;5 cm can be preserved at a much higher rate. Moreover, this surgical procedure is oncologically safe in terms of mid-term recurrence and CSM-free survival rates. This data undermines the growing evidence of limited PC-RPLND being justifiable in strictly unilateral residual mass &lt;5 cm. This data has to be confirmed with a longer follow-up regarding in-field and retroperitoneal recurrences.

Preservation of Ejaculatory Function After Postchemotherapy Retroperitoneal Lymph Node Dissection (PC-RPLND) in Patients With Testicular Cancer: Template vs. Bilateral Resection

Background: The role of lymph node dissection (LND) for renal cell carcinoma (RCC) is controversial. Notably, the conflicting evidence on the benefits and harms of LND is inherently linked to the lack of consensus on both anatomic templates and extent of lymphadenectomy. Herein, we provide a detailed overview of the most commonly dissected templates of LND for RCC, focusing on key anatomic landmarks and patterns of lymphatic drainage.Methods: A systematic review of the English-language literature was performed without time filters in July 2018 in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement recommendations. The primary endpoint was to summarize the most commonly dissected templates of LND according to the side of RCC.Results: Overall, 25 studies were selected for qualitative analysis. Of these, most were retrospective. The LND template was heterogeneous across studies. Indications and extent of LND were either not reported or not standardized in most series. The most commonly dissected template for right-sided tumors included hilar, paracaval, and precaval nodes, with few authors extending the dissection to the inter-aortocaval, retrocaval, common iliac or pre/paraaortic nodes. Similarly, the most commonly dissected template for left-sided tumors encompassed the renal hilar, preaortic and paraaortic nodes, with few authors reporting a systematic dissection of inter-aortocaval, retro-aortic, common iliac, or para-caval nodes.Conclusions: In light of the unpredictable renal lymphatic anatomy and the evidence from available prospective mapping studies, the extent of the most commonly dissected templates might be insufficient to catch the overall anatomic pattern of lymphatic drainage from RCC.

Background: The role of lymph node dissection (LND) for renal cell carcinoma (RCC) is controversial. Notably, the conflicting evidence on the benefits and harms of LND is inherently linked to the lack of consensus on both anatomic templates and extent of lymphadenectomy. Herein, we provide a detailed overview of the most commonly dissected templates of LND for RCC, focusing on key anatomic landmarks and patterns of lymphatic drainage.Methods: A systematic review of the English-language literature was performed without time filters in July 2018 in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement recommendations. The primary endpoint was to summarize the most commonly dissected templates of LND according to the side of RCC.Results: Overall, 25 studies were selected for qualitative analysis. Of these, most were retrospective. The LND template was heterogeneous across studies. Indications and extent of LND were either not reported or not standardized in most series. The most commonly dissected template for right-sided tumors included hilar, paracaval, and precaval nodes, with few authors extending the dissection to the inter-aortocaval, retrocaval, common iliac or pre/paraaortic nodes. Similarly, the most commonly dissected template for left-sided tumors encompassed the renal hilar, preaortic and paraaortic nodes, with few authors reporting a systematic dissection of inter-aortocaval, retro-aortic, common iliac, or para-caval nodes.Conclusions: In light of the unpredictable renal lymphatic anatomy and the evidence from available prospective mapping studies, the extent of the most commonly dissected templates might be insufficient to catch the overall anatomic pattern of lymphatic drainage from RCC.

Templates of Lymph Node Dissection for Renal Cell Carcinoma: A Systematic Review of the Literature

Introduction: Lymph node metastases (LNM) represent a proven prognostic factor for biochemical recurrence (BCR)-free survival, metastatic free survival and overall survival in prostate cancer (PCa). Although pelvic node dissection remains the gold standard for the detection of LNM, novel imaging techniques are entering clinical practice, in the effort to improve LNM detection and spare unnecessary surgeries. Aim of the current review is to describe such imaging techniques and explore their advantages and limitations.Evidence Acquisition: The National Library of Medicine Database was searched for relevant articles published between January 2013 and August 2018. A wide search was performed including the combination of following words: “Prostate” and “Cancer” and “staging” and “Lymph Node” and “imaging” and (“MRI” or “PET”). The initial list of selected papers was enriched by individual suggestions of the authors of the present review.Evidence Synthesis: DWI-MRI in detection of lymph node invasion has a sensitivity and specificity of 41 and 94%, respectively. For SPIO MRI using ferumoxtran-10, the sensitivity for detection of LNM with short axis diameter of 5–10 mm is reported at 96.4%, compared to 28.5% with MRI alone. PSMA PET/CT is growing exponentially, both in the initial detection of LNM and for BCR evaluation. Fluciclovine PET could improve detection of subcentimetric pathologic lymph nodes. Sentinel lymph node techniques remain experimental and not validated in the field of PCa.Conclusions: Molecular imaging, particularly PSMA ligand PET imaging, present interesting diagnostic accuracy in LN diagnosis even in subcentimetric LN. DWI-MRI yields good results in LN involvement evaluation and the use of contrast agent such SPIO may improve the detection rate. The SLN technique is limited to experimental protocols and for intermediate or high-risk PCa. Prospective trials are awaited to evaluate the true clinical impact of these imaging techniques on PCa oncologic outcomes.

Introduction: Lymph node metastases (LNM) represent a proven prognostic factor for biochemical recurrence (BCR)-free survival, metastatic free survival and overall survival in prostate cancer (PCa). Although pelvic node dissection remains the gold standard for the detection of LNM, novel imaging techniques are entering clinical practice, in the effort to improve LNM detection and spare unnecessary surgeries. Aim of the current review is to describe such imaging techniques and explore their advantages and limitations.Evidence Acquisition: The National Library of Medicine Database was searched for relevant articles published between January 2013 and August 2018. A wide search was performed including the combination of following words: “Prostate” and “Cancer” and “staging” and “Lymph Node” and “imaging” and (“MRI” or “PET”). The initial list of selected papers was enriched by individual suggestions of the authors of the present review.Evidence Synthesis: DWI-MRI in detection of lymph node invasion has a sensitivity and specificity of 41 and 94%, respectively. For SPIO MRI using ferumoxtran-10, the sensitivity for detection of LNM with short axis diameter of 5–10 mm is reported at 96.4%, compared to 28.5% with MRI alone. PSMA PET/CT is growing exponentially, both in the initial detection of LNM and for BCR evaluation. Fluciclovine PET could improve detection of subcentimetric pathologic lymph nodes. Sentinel lymph node techniques remain experimental and not validated in the field of PCa.Conclusions: Molecular imaging, particularly PSMA ligand PET imaging, present interesting diagnostic accuracy in LN diagnosis even in subcentimetric LN. DWI-MRI yields good results in LN involvement evaluation and the use of contrast agent such SPIO may improve the detection rate. The SLN technique is limited to experimental protocols and for intermediate or high-risk PCa. Prospective trials are awaited to evaluate the true clinical impact of these imaging techniques on PCa oncologic outcomes.

Current Imaging Techniques for Lymph Node Staging in Prostate Cancer: A Review

Lymph node dissection (LND; PLND: pelvic LND) is an essential component of radical cystectomy (RC) for bladder cancer (BC). However, the optimal anatomical extent of LND and its potential therapeutic role are still controversial: as we will explain, the extent of LND dissection is a predictor of survival and local recurrence but what is an adequate extension is still unclear. Moreover, there is large uncertainty about the role of surgery in patients with clinically-positive nodes. In this review we will provide a synthesis of the available evidence on this highly debated topic. Overall, the studies presented in this work support the idea that extended lymphadenectomy could provide optimal diagnostic and possibly therapeutic results in cN- patients. In cN+ patients, post chemotherapy surgery may be considered especially in subjects who have a good response to CHT, although definitive evidence is still needed. Finally, the final results of randomized trials are eagerly awaited to draw definitive conclusions of the role of PLND in BC.

Lymph node dissection (LND; PLND: pelvic LND) is an essential component of radical cystectomy (RC) for bladder cancer (BC). However, the optimal anatomical extent of LND and its potential therapeutic role are still controversial: as we will explain, the extent of LND dissection is a predictor of survival and local recurrence but what is an adequate extension is still unclear. Moreover, there is large uncertainty about the role of surgery in patients with clinically-positive nodes. In this review we will provide a synthesis of the available evidence on this highly debated topic. Overall, the studies presented in this work support the idea that extended lymphadenectomy could provide optimal diagnostic and possibly therapeutic results in cN- patients. In cN+ patients, post chemotherapy surgery may be considered especially in subjects who have a good response to CHT, although definitive evidence is still needed. Finally, the final results of randomized trials are eagerly awaited to draw definitive conclusions of the role of PLND in BC.

The Role of Lymph Node Dissection in the Treatment of Bladder Cancer

Objectives: To evaluate the frequency and distribution of pelvic nodes metastases, in intermediate-high risk prostate cancer (PCa) patients (pts), who underwent open radical prostatectomy (ORP) and superextended pelvic lymph node dissection (sePLND).Patients and Methods: We retrospectively evaluated 630 consecutive pts with clinically localized, intermediate-high risk PCa, treated with ORP and sePLND from 2009 to 2016 at a single institution. The sePLND always removed all nodal/fibro-fatty tissue of the internal iliac, external iliac, obturator, common iliac, and presacral regions.Results: Positive lymph nodes (LN+) were found in 133 pts (21.1%). The median number of removed nodes and LN+ was 25 and 1, respectively. LN+ were found in 64 (48.1%), 58 (43.6%), 53 (39.8%), 16 (12%), and 20 (15%) pts and were present as a single site in 27 (20.3%), 22 (16.5%), 20 (15%), 0, and 6 (4.5%) cases in the internal iliac, external iliac, obturator, common iliac, and presacral chain, respectively. An ePLND would have correctly staged 127 (95%) pts but removed all LN+ in only 97 (73%) pts. Presacral nodes harbored LN+ in 20 patients. Among them, 18 were high-risk patients. Moreover, all but 1 pts with common iliac LN+ were in high risk group.Conclusions: These results suggest that removal of presacral and common iliac nodes could be omitted in intermediate risk pts. However, a PLND limited to external iliac, obturator, and internal iliac region may be adequate for nodal staging purpose, but not enough accurate if we aim to remove all possible site of LN+ in high risk pts.

Objectives: To evaluate the frequency and distribution of pelvic nodes metastases, in intermediate-high risk prostate cancer (PCa) patients (pts), who underwent open radical prostatectomy (ORP) and superextended pelvic lymph node dissection (sePLND).Patients and Methods: We retrospectively evaluated 630 consecutive pts with clinically localized, intermediate-high risk PCa, treated with ORP and sePLND from 2009 to 2016 at a single institution. The sePLND always removed all nodal/fibro-fatty tissue of the internal iliac, external iliac, obturator, common iliac, and presacral regions.Results: Positive lymph nodes (LN+) were found in 133 pts (21.1%). The median number of removed nodes and LN+ was 25 and 1, respectively. LN+ were found in 64 (48.1%), 58 (43.6%), 53 (39.8%), 16 (12%), and 20 (15%) pts and were present as a single site in 27 (20.3%), 22 (16.5%), 20 (15%), 0, and 6 (4.5%) cases in the internal iliac, external iliac, obturator, common iliac, and presacral chain, respectively. An ePLND would have correctly staged 127 (95%) pts but removed all LN+ in only 97 (73%) pts. Presacral nodes harbored LN+ in 20 patients. Among them, 18 were high-risk patients. Moreover, all but 1 pts with common iliac LN+ were in high risk group.Conclusions: These results suggest that removal of presacral and common iliac nodes could be omitted in intermediate risk pts. However, a PLND limited to external iliac, obturator, and internal iliac region may be adequate for nodal staging purpose, but not enough accurate if we aim to remove all possible site of LN+ in high risk pts.

Difference in Frequency and Distribution of Nodal Metastases Between Intermediate and High Risk Prostate Cancer Patients: Results of a Superextended Pelvic Lymph Node Dissection

BackgroundPositive nodal status (pN1) is an independent predictor of survival in renal cell carcinoma (RCC) patients. However, no study to date has tested whether the location of lymph node (LN) metastases does affect oncologic outcomes in a population submitted to radical nephrectomy (RN) and extended lymph node dissection (eLND).</sec>ObjectiveTo describe nodal disease dissemination in clear cell RCC (ccRCC) patients and to assess the effect of the anatomical sites and the number of nodal areas affected on cancer specific mortality (CSM).</sec>Design, setting and partecipantsThe study included 415 patients who underwent RN and eLND, defined as the removal of hilar, side-specific (pre/paraaortic or pre/paracaval) and interaortocaval LNs for ccRCC, at two institutions.</sec>Outcome measurement and statistical analysisDescriptive statistics were used to depict nodal dissemination in pN1 patients, stratified according to nodal site and number of involved areas. Multivariable Cox regression analyses and Kaplan-Meier curves were used to explore the relationship between pN1 disease features and survival outcomes.</sec>Results and limitationsMedian number of removed LN was 14 (IQR 9–19); 23% of patients were pN1. Among patients with one involved nodal site, 54 and 26% of patients were positive only in side-specific and interaortocaval station, respectively. The most frequent nodal site was the interaortocaval and side-specific one, for right and left ccRCC, respectively. Interaortocaval nodal positivity (HR 2.3, CI 95%: 1.3–3.9, p < 0.01) represented an independent predictor of CSM.</sec>ConclusionsWhen ccRCC patient harbour nodal disease, its spreading can occur at any nodal station without involving the others. The presence of interoartocaval positive nodes does affect oncologic outcomes.</sec>Patient summaryLymph node invasion in patients with clear cell renal cell carcinoma is not following a fixed anatomical pattern. An extended lymph node dissection, during treatment for primary kidney tumour, would aid patient risk stratification and multimodality upfront treatment.</sec>

Background: Positive nodal status (pN1) is an independent predictor of survival in renal cell carcinoma (RCC) patients. However, no study to date has tested whether the location of lymph node (LN) metastases does affect oncologic outcomes in a population submitted to radical nephrectomy (RN) and extended lymph node dissection (eLND).Objective: To describe nodal disease dissemination in clear cell RCC (ccRCC) patients and to assess the effect of the anatomical sites and the number of nodal areas affected on cancer specific mortality (CSM).Design, setting and partecipants: The study included 415 patients who underwent RN and eLND, defined as the removal of hilar, side-specific (pre/paraaortic or pre/paracaval) and interaortocaval LNs for ccRCC, at two institutions.Outcome measurement and statistical analysis: Descriptive statistics were used to depict nodal dissemination in pN1 patients, stratified according to nodal site and number of involved areas. Multivariable Cox regression analyses and Kaplan-Meier curves were used to explore the relationship between pN1 disease features and survival outcomes.Results and limitations: Median number of removed LN was 14 (IQR 9–19); 23% of patients were pN1. Among patients with one involved nodal site, 54 and 26% of patients were positive only in side-specific and interaortocaval station, respectively. The most frequent nodal site was the interaortocaval and side-specific one, for right and left ccRCC, respectively. Interaortocaval nodal positivity (HR 2.3, CI&nbsp;95%: 1.3–3.9, p &lt; 0.01) represented an independent predictor of CSM.Conclusions: When ccRCC patient harbour nodal disease, its spreading can occur at any nodal station without involving the others. The presence of interoartocaval positive nodes does affect oncologic outcomes.Patient summary: Lymph node invasion in patients with clear cell renal cell carcinoma is not following a fixed anatomical pattern. An extended lymph node dissection, during treatment for primary kidney tumour, would aid patient risk stratification and multimodality upfront treatment.