Increasing rate of lymph node invasion in patients with prostate cancer treated with radical prostatectomy and lymph node dissection

Objectives

To investigate lymph node invasion (LNI) rates in prostate cancer (PCa) patients. Recent studies demonstrated an inverse stage migration in PCa patients toward more advanced and unfavorable diseases. We hypothesized that this trend is also evident in LNI rates, in PCa patients treated with radical prostatectomy (RP) and pelvic lymph node dissection (PLND).

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

Background

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

Objective

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

Design, setting, and participants

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

Intervention

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

Measurements

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

Results and limitations

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

Conclusions

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

A population-based assessment of the National Comprehensive Cancer Network practice guideline indications for pelvic lymph node dissection at radical prostatectomy

Study Type – Therapy (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? The National Comprehensive Cancer Network guidelines recommend pelvic lymph node dissection in patients with a nomogram‐predicted lymph node invasion risk of 2% or more. We set out to examine the validity of this recommendation. OBJECTIVES

• ? To examine the ability of the threshold recommended by the National Comprehensive Cancer Network (NCCN) in correctly predicting histologically‐confirmed lymph node invasion (LNI).
• ? The 2010 NCCN practice guidelines for prostate cancer recommend a pelvic lymph node dissection (PLND) at radical prostatectomy in all individuals with a nomogram predicted LNI risk of ≥2%.

PATIENTS AND METHODS

• ? We assessed 20 877 patients who were treated with radical prostatectomy and PLND between 2004 and 2006, within the Surveillance, Epidemiology and End Results database.
• ? The 2% nomogram threshold, as well as other threshold values (range 1–10%) were tested.
• ? Finally, we externally validated the NCCN guideline nomogram.

RESULTS

• ? Overall, 2.5% of patients had LNI.
• ? The use of the 2% threshold would allow the avoidance of 23% of PLNDs, at the cost of missing 1.7% of patients with LNI. Conversely, the use of a 3% threshold would allow the avoidance of 58% of PLNDs, at the cost of missing 15% of patients with LNI vs 72% and 26%, respectively, for the 4% threshold.
• ? Overall, the accuracy of the NCCN guideline nomogram quantified according to the receiver‐operator characteristics‐derived area under the curve was 82%.

CONCLUSIONS

• ? In a population‐based sample, the NCCN guideline nomogram is highly accurate.
• ? However, the 2% threshold will permit the avoidance of only 23% of PLNDs, instead of the 48% intended by the NCCN guidelines.
• ? The use of a 3% threshold may allow a lower rate of PLND overtreatment, although it will miss more patients with LNI.

     

Pattern of node metastases in patients treated with radical cystectomy and extended or superextended pelvic lymph node dissection due to bladder cancer

Background

Pelvic lymph node dissection (PLND) has a diagnostic and therapeutic role during radical cystectomy in bladder cancer patients. However, at the time, no prospective data supports the value of extended PLND in improving survival expectances. We sought to describe incidence and location of node metastases in patients treated with extended and superextended PLND.

Multicenter evaluation of guideline adherence for pelvic lymph node dissection in patients undergoing open retropubic vs. laparoscopic or robot assisted radical prostatectomy according to the recent German S3 guideline on prostate cancer

Purpose

Pelvic lymph node dissection (PLND) is recommended for patients with prostate cancer (PCa) and significant risk for nodal metastases. This study aimed to assess guideline adherence regarding PLND according to the German S3 guideline as example for a national but highly used guideline on prostate cancer and to compare the rate of complications different approaches for radical prostatectomy (RP).

Methods

Patients undergoing open (RRP), laparoscopic (LARP) or robot-assisted (RARP) RP in six centers in Germany and Austria were included. The primary endpoint was the total number of removed lymph nodes (LN) between the different surgical approaches according to recent guideline recommendations. Secondary endpoints were the number of patients undergoing a sufficient PLND, defined as a removal of at least 10 LN and associated complication rates.

Results

2634 patients undergoing RP were included (RRP: 66%, RARP/LARP: 34%). PLND was performed in 88% (RRP: 88.5%, RARP/LARP: 86.8%, p = 0.208). In intermediateor high risk PCa, PLND was performed in 97.2% (RRP: 97.7%, RARP/LARP: 96.2, p = 0.048). Of those, the mean number of LN was 19 (RRP: 19 vs. RARP/LARP: 17, p < 0.005) and sufficient PLND was observed in 84.6% of RRP compared to 77.2% of RARP/LARP (p < 0.005). Symptomatic lymphoceles requiring surgical treatment occurred more often in RRP than in RARP/LARP (4.0% vs. 1.6%, p = 0.001).

Conclusions

The general guideline adherence regarding performing PNLD and the LN yield is high, regardless of the surgical approach. As expected, lymph node yield was higher when very experienced surgeons conducted the procedure. This should be considered in patients’ counseling.

     

Critical assessment of the European Association of Urology guideline indications for pelvic lymph node dissection at radical prostatectomy

Study Type – Prognosis (retrospective cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Lymphadenectomy is the most accurate lymph node staging procedure in patients with prostate cancer. We presented the first formal validation of the 2010 European Association of Urology guidelines for lymphadenectomy in prostate cancer patients.

OBJECTIVE

? To assess the 2010 European Association of Urology (EAU) guidelines for prostate cancer, which recommend a pelvic lymph node dissection (PLND) at radical prostatectomy in all individuals with a nomogram‐predicted lymph node invasion (LNI) risk of >7%.

PATIENTS and methods

? We focused on 1520 patients treated with radical prostatectomy and PLND, between 2006 and 2010, at a single European institution. We examined the ability of the EAU proposed threshold to correctly predict histologically confirmed LNI. Moreover, we tested the ability of a range of nomogram thresholds between 1 and 14% to correctly predict histologically confirmed LNI. Finally, we externally validated the EAU PLND guideline nomogram.

RESULTS

? Overall, 10.6% of patients had LNI. The use of the 7% limit would have allowed the avoidance of 49% of PLNDs, at the cost of missing 11% of patients with LNI. The use of thresholds of 6% and 8% would have allowed the avoidance of respectively 46% and 52% of PLNDs, at the cost of missing respectively 9% and 11% of patients with LNI. Overall, the accuracy of the EAU guideline nomogram according to the receiver operating characteristics derived area under curve was 81%

CONCLUSION

? Our observations indicate that the EAU guideline nomogram is highly accurate. The recommended threshold of 7%, above which a PLND should be performed, is associated with a favourable compromise between avoidable PLNDs and potentially missed LNI cases.     

Updated nomogram predicting lymph node invasion in patients with prostate cancer undergoing extended pelvic lymph node dissection: the essential importance of percentage of positive cores

Background

Few predictive models aimed at predicting the presence of lymph node invasion (LNI) in patients with prostate cancer (PCa) treated with extended pelvic lymph node dissection (ePLND) are available to date.

Objective

Update a nomogram predicting the presence of LNI in patients treated with ePLND at the time of radical prostatectomy (RP).

Design, setting, and participants

The study included 588 patients with clinically localised PCa treated between September 2006 and October 2010 at a single tertiary referral centre.

Intervention

All patients underwent RP and ePLND invariably including removal of obturator, external iliac, and hypogastric nodes.

Measurements

Prostate-specific antigen, clinical stage, and primary and secondary biopsy Gleason grade as well as percentage of positive cores were included in univariable (UVA) and multivariable (MVA) logistic regression models predicting LNI and formed the basis for the regression coefficient-based nomogram. The area under the curve (AUC) method was used to quantify the predictive accuracy (PA) of the model.

Results and limitations

The mean number of lymph nodes removed and examined was 20.8 (median: 19; range: 10-52). LNI was found in 49 of 588 patients (8.3%). All preoperative PCa characteristics differed significantly between LNI-positive and LNI-negative patients (all p < 0.001). In UVA predictive accuracy analyses, percentage of positive cores was the most accurate predictor of LNI (AUC: 79.5%). At MVA, clinical stage, primary biopsy Gleason grade, and percentage of positive cores were independent predictors of LNI (all p ≤ 0.006). The updated nomogram demonstrated a bootstrap-corrected PA of 87.6%. Using a 5% nomogram cut-off, 385 of 588 patients (65.5%) would be spared ePLND. and LNI would be missed in only 6 patients (1.5%). The sensitivity, specificity, and negative predictive value associated with the 5% cut-off were 87.8%, 70.3%, and 98.4%, respectively. The relatively low number of patients included as well as the lack of an external validation represent the main limitations of our study.

Conclusions

We report the first update of a nomogram predicting the presence of LNI in patients treated with ePLND. The nomogram maintained high accuracy, even in more contemporary patients (87.6%). Because percentage of positive cores represents the foremost predictor of LNI, its inclusion should be mandatory in any LNI prediction model. Based on our model, those patients with a LNI risk < 5% might be safely spared ePLND.     

Lymph node dissection should not be dismissed in case of localized renal cell carcinoma in the presence of larger diseases

Objective

To assess whether even in the group of localized renal cell carcinoma (RCC), some patients might harbor a disease with a predilection for lymph node invasion (LNI) and/or lymph node (LN) progression and might deserve lymph node dissection (LND) at the time of surgery.

Outcomes and complications of pelvic lymph node dissection during robotic-assisted radical prostatectomy

Purpose

Describe the outcomes and complications of patients who underwent standard pelvic lymphadenectomy (SPLND) and extended PLND (EPLND), or who did not undergo PLND (non-PLND) at the time of robotic-assisted laparoscopic radical prostatectomy (RALP).

Methods

Retrospective analysis of prospectively collected longitudinal data of 492 RALPs performed by a single surgeon (Kane) over a 5-year period. Patients are subdivided into three treatment groups: 54 EPLND; 231 SPLND; and 207 non-PLND. Indications for EPLND include Gleason score ≥8, PSA ≥10 ng/mL, and higher D’Amico risk group. Patient demographics, perioperative complications, and short-term oncologic outcomes are compared.

Results

Patients who underwent EPLND had higher-risk prostate cancer as evidenced by higher mean PSA (8.5 ng/mL), biopsy Gleason sum (≥8) (57.7 %), and D’Amico risk group (75.9 %), compared to SPLND and/or non-PLND groups (p ≤ 0.001). The EPLND total lymph node yield was similar compared to SPLND (20 vs. 18; p = 0.070). When the EPLND (n = 41) and SPLND (n = 57) were examined among only high-risk patients, the lymph node (IQR) yields [20 (14–29) vs. 17 (12–23)] and the proportion of positive nodes [29.3 % (12/41) vs. 12.3 % (7/57)] differed significantly (p = 0.048 and p = 0.042, respectively). Complication rates for all groups were similar and lymphocele formation was 5 %; 2.5 % were clinically significant.

Conclusions

Robotic PLND can be performed with nodal yield comparable to open or laparoscopic PLND. Robotic EPLND improves nodal yield and the proportion of high-risk patients with nodal metastases recognized. Robotic PLND is associated with an approximately 5 % lymphocele rate. There is no difference in complications between EPLND and SPLND.     

Lymph node yield during radical prostatectomy does not impact rate of biochemical recurrence in patients with seminal vesicle invasion and node-negative disease

Objectives

Seminal vesicle invasion (SVI) is a risk factor for poor oncologic outcome in patients with prostate cancer. Modifications to the pelvic lymph node dissection (PLND) during radical prostatectomy (RP) have been reported to have a therapeutic benefit. The present study is the first to determine if lymph node yield (LNY) is associated with a lower risk of biochemical recurrence (BCR) for men with SVI.

Extent of pelvic lymph node dissection and the impact of standard template dissection on nomogram prediction of lymph node involvement

Background

Our current lymph node involvement (LNI) nomogram was created using patients receiving both limited and standard lymph node dissection (LND). Over time, refinements in technique could affect the diagnostic yield from LND.

Objective

Our aim was to validate our existing LNI nomogram or develop a new nomogram with updated prediction coefficients that reflect the current standard LND template during radical prostatectomy (RP). We hypothesized that the existing nomogram would demonstrate good discrimination but poor calibration in a contemporary series of standard LND.

Design, setting, and participants

A retrospective analysis of 4176 consecutive primary RP patients was performed, including open procedures (3097 patients from 2000 to 2008) and laparoscopic procedures (1079 patients from 2005 to 2008). After excluding 127 patients (3%) with limited LND, 10 (0.2%) with pretreatment prostate-specific antigen (PSA) >50 ng/ml, and 318 (8%) with incomplete data, the final cohort totaled 3721 patients. The nomograms were evaluated using receiver operating characteristic analysis, calibration plots, and decision-curve analysis.

Interventions

Patients received open or laparoscopic (conventional and robot-assisted) RP and standard LND in our center.

Measurements

Assessments were obtained using preoperative PSA, biopsy Gleason score, and clinical stage.

Results and limitations

The median number of nodes removed was 11, with ∼60% of patients having at least 10 nodes removed (n = 2224). Overall, 5.2% of patients (n = 194) had positive lymph nodes. The new nomogram had very high discriminative accuracy (area under the curve: 0.862). The decision-curve analysis showed that the new nomogram had the highest clinical net benefit for all reasonable threshold probabilities.

Conclusions

The new nomogram shows improved calibration when predicting lymph node invasion in a contemporary cohort of patients with prostate cancer exclusively treated with RP and standard LND. This nomogram will be used as the preferred predictive model for counseling patients and developing studies at our institution.     

Lymphadenectomy in Gleason 7 prostate cancer: Adherence to guidelines and effect on clinical outcomes

Background

To examine usage trends, guideline adherence, and survival data for patients undergoing lymphadenectomy (LND) at the time of radical prostatectomy (RP) for Gleason 7 prostate cancer (PCa).

Reconsidering the role of pelvic lymph node dissection with radical prostatectomy for prostate cancer in an era of improving radiological staging techniques

Background

Performing an extended pelvic lymph node dissection (PLND) on all men with intermediate- and high-risk prostate cancer at the time of a radical prostatectomy (RP) remains controversial. The majority of patients PLND histology is benign, and the long-term cancer-free progression in men with positive lymph node metastasis is low. The objective is to investigate the probability of long-term biochemical freedom from recurrent disease (bNED) in men with lymph node metastasis identified at the time of radical prostatectomy (RP).

Subjects and methods

A retrospective review of the pathology of 1184 pelvic lymph node dissections performed at the time of a radical prostatectomy by multiple surgeons referred to a single uro-pathology laboratory between 2008 and 2014 identified 61 men with node-positive prostate cancer. Of the men with positive nodes, 24 had a standard PLND and 37 an extended PLND (ePLND). bNED was defined as a post-operative serum PSA < 0.2 ng/ml.

Results

The median follow-up is 4 years (2–8). The median lymph node count was 7 (range 2–16) for PLND and 22 (range 6–46) for the ePLND. A single lymph node metastasis was identified in 56% of the 61 men. Only 10% of men with a positive lymph node metastasis remained free of biochemical recurrence of disease, and only 5% had undetectable serum PSA. There was no difference in bNED outcome between a PLND and ePLND. The number of men needed to be treated with a PLND at the time of RP (NNT) to result in an undetectable post-operative PSA at a median follow-up of 4 years is 395.

Conclusions

In men with lymph node metastasis, the probability of long-term bNED is low and the NNT for cure is high. With emerging improved radiological imaging techniques increasing the detection of lymph node metastasis outside the extended lymph node dissection templates, more scientific investigation is required to evaluate which men will benefit from a PLND and which men can avoid an unnecessary PLND procedure.

     

The extent of pelvic lymph node dissection correlates with the biochemical recurrence rate in patients with intermediate- and high-risk prostate cancer

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Pelvic lymph‐node dissection during radical prostatectomy for prostate cancer is certainly a fundamental staging procedure but its therapeutic role is yet under debate. This retrospective study suggests that, in patients with intermediate‐ and high‐risk of prostate cancer, the greater the number of lymph‐nodes removed, the lower the risk of biochemical relapse, even in the presence of 1 or 2 lymph‐node metastasis. However, the Will Rogers phenomenon must be considered due to the retrospective nature of the present study.

OBJECTIVE

• ? To assess the impact of pelvic lymph node dissection (PLND) and of the number of lymph nodes (LNs) retrieved during radical prostatectomy (RP) on biochemical relapse (BCR) in pNX/0/1 patients with prostate cancer according to the clinical risk of lymph node invasion (LNI).

PATIENTS AND METHODS

• ? We evaluated 872 pT2‐4 NX/0/1 consecutive patients submitted to RP between October 1995 and June 2009, with the following inclusion criteria: (i) a follow‐up period ≥12 months; (ii) the avoidance of neoadjuvant hormonal therapy or adjuvant hormonal and/or adjuvant radiotherapy; (iii) the availability of complete follow‐up data; (iv) no pathological T0 disease; (v) complete data regarding the clinical stage and Gleason score (Gs), the preoperative prostate‐specific antigen (PSA) level and the pathological stage.
• ? The patients were stratified as having low risk (cT1a‐T2a and cGs ≤6 and PSA level < 10 ng/mL), intermediate risk (cT2b‐T2c or cGs = 7 or PSA level = 10–19.9) or high risk of LNI (cT3 or cGs = 8–10 or PSA level ≥ 20).
• ? The 872 patients were divided into two LN groups according to the number of LNs retrieved: group 1 had no LN or one to nine LNs removed; group 2 had 10 or more LNs.
• ? The variables analysed were LN group, age, PSA level, clinical and pathological stage and Gs, surgical margin status, LN status and number of LN metastases; the primary endpoint was the BCR‐free survival.

RESULTS

• ? The mean follow‐up was 55.8 months.
• ? Of all the patients, 305 (35%) were pNx and 567 (65.0%) were pN0/1.
• ? Of the 567 patients submitted to PLND, the mean number of LNs obtained was 10.9, and 49 (8.6%) were pN1.
• ? In the 402 patients at low risk of LNI, LN group was not a significant predictor of BCR at univariate analysis, while in the 470 patients at intermediate and high risk of LNI, patients with ≥10 LNs removed had a significantly lower BCR‐free survival at univariate and multivariate analysis.

CONCLUSION

• ? In our study population, a more extensive PLND positively affects the BCR‐free survival regardless of the nodal status in intermediate‐ and high‐risk prostate cancer.

     

Extent of pelvic lymph node dissection in penile cancer may impact survival

Introduction

Current guidelines on management of penile carcinoma (PC) recommend ipsilateral pelvic lymph node dissection (PLND) in patients with inguinal lymph node metastasis (LNM) who meet specific criteria. The aim of this article was to assess outcomes in patients treated with bilateral PLND in the presence of unilateral metastatic pelvic nodes.

Methods

After IRB approval, four international centers contributed to this study. Men with PC and unilateral inguinal LNM and pelvic node metastases were retrospectively analyzed. Estimates of overall survival (OS) and cancer-specific survival were provided by the Kaplan–Meier method. Comparisons between subgroups were made using the log-rank test, and Cox regression analysis was used to adjust comparisons for covariates of interest.

Results

From 1978 to 2012, fifty-one men with unilateral inguinal LNM and positive pelvic nodes on PLND were identified. Thirty-eight (75 %) had ipsilateral and 13 (25 %) had bilateral PLND. Except the extent of the PLND, patients were comparable with respect to disease and therapeutic interventions. The Kaplan–Meier estimated median OS was significantly longer in the bilateral PLND patients (21.7 vs. 13.1, p = 0.051). On Cox regression analysis, bilateral PLND [HR 0.25, (95 % CI 0.10–0.64)], multiple pelvic node involvement [HR 2.12 (95 % CI 1.02–4.43)], neoadjuvant chemotherapy [HR 0.01, (95 % CI 0.02–0.44)] and adjuvant therapies [HR 0.16, (95 % CI 0.06–0.45)] (compared to no additional therapy) were independent predictors of OS.

Conclusions

Men with PC and pelvic node metastases may benefit from a bilateral PLND. This hypothesis requires further confirmation.

     

Adjuvant pelvic radiation is associated with improved survival and decreased disease recurrence in pelvic node-positive penile cancer after lymph node dissection: A multi-institutional study

Purpose

Few studies have examined the role of radiation therapy in advanced penile squamous cell carcinoma. We sought to evaluate the association of adjuvant pelvic radiation with survival and recurrence for patients with penile cancer and positive pelvic lymph nodes (PLNs) after lymph node dissection.

Evaluating the accuracy of intraoperative frozen section during inguinal lymph node dissection in penile cancer

Introduction

Inguinal lymph node dissection is an integral part in the management of invasive penile tumors with intraoperative assessment often aiding decision-making during dissection. In this study, we evaluate the diagnostic value of intraoperative frozen section (FS) and analyze clinicopathologic factors that affect its accuracy.

Disparity between pre-existing management of penile cancer and NCCN guidelines

Objective

To determine the locoregional management of penile cancer before the introduction of NCCN guidelines and how much shift in practice patterns is required to meet the guidelines.

Role of surgical approach on lymph node dissection yield and survival in patients with upper tract urothelial carcinoma

Objectives

With increasing utilization of robot-assisted surgery in urologic oncology, robotic nephroureterectomy (RNU) is becoming the surgical modality of choice for patients with upper tract urothelial carcinoma (UTUC). The role of surgical approach on lymph node dissection (LND) and lymph node (LN) yield is unclear, and potential therapeutic effects are unknown. Here we analyze the effects of surgical approach on LN yield, performance of LND, and overall survival (OS).

Impact of adequate pelvic lymph node dissection on overall survival after radical cystectomy: A stratified analysis by clinical stage and receipt of neoadjuvant chemotherapy

Purpose

An adequate pelvic lymph node dissection (LND) during radical cystectomy (RC) for muscle-invasive bladder cancer (BCa) has been shown to provide a survival benefit. We designed a study to assess the effect of adequate LND on overall survival (OS) according to cT stage and receipt of neoadjuvant chemotherapy (NAC).