Validation of a nomogram predicting the probability of lymph node invasion based on the extent of pelvic lymphadenectomy in patients with clinically localized prostate cancer

OBJECTIVE: To develop a multivariate nomogram to predict the rate of lymph node invasion (LNI) in patients with clinically localized prostate cancer according to the extent of extended pelvic lymphadenectomy (PLND), which is associated with significantly higher rate of LNI. PATIENTS AND METHODS: The study comprised 781 consecutive patients (median age 66.6 years, range 45-85) treated with PLND and radical retropubic prostatectomy (RRP) for clinically localized prostate cancer. Their median (range) prostate-specific antigen (PSA) level was 7 (1.03-49.91) ng/mL, and their clinical stages were T1c in 433 (55.4%), T2 in 328 (42%) and T3 in 20 (2.6%). Biopsy Gleason sums were 相似文献   

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.     

Obesity does not increase the risk of lymph node metastases in patients with clinically localized prostate cancer undergoing radical prostatectomy and extended pelvic lymph node dissection

Objectives: Several studies have shown that obesity is associated with more aggressive prostate cancer (PCa) variants. We hypothesized that obesity, quantified as body mass index (BMI), is associated with a higher risk of lymph node invasion (LNI) in patients undergoing extended pelvic lymph node dissection (ePLND). Methods: Clinical and pathological data were available for 994 consecutive men with PCa treated with radical prostatectomy (RP) and ePLND at a single European tertiary academic centre. Univariable and multivariable logistic regression analyses addressed the rate of LNI. Covariates consisted of pre‐treatment prostate specific antigen (PSA), biopsy Gleason sum, clinical stage history of diabetes mellitus as well as BMI coded as either continuous or categorized (<25, 25.0–29.9, 30 kg/m² or more) variable. Predictive accuracy was assessed with area under curve estimates. Results: Overall LNI was diagnosed in 105 patients (10.6%). Mean number of removed lymph nodes was 18.3 (range 7–60). Of all 994 patients, 372 (37.4%) were normal weight, 518 (52.1%) overweight, and 104 (10.5%) were clinically obese. Prevalence of LNI did not significantly differ across different BMI categories (<25, 25.0–29.9 and 30 kg/m² or more; 9.9, 10.6 and 12.5%, respectively; P = 0.75). In logistic regression models, neither continuously coded nor categorized BMI was a significant predictor of LNI at univariable or multivariable analyses (all P‐values ≥0.1). Moreover, inclusion of BMI with PSA, clinical stage, biopsy Gleason sum and presence of DM did not increase the ability of these variables to predict LNI (82.2% without BMI vs 82.5% and 82.9% with BMI coded as continuous and categorized variable, respectively; all P ≥ 0.4). Conclusions: In men undergoing RP and ePLND, increased BMI was not associated with increased risk of lymph node metastases. Therefore, routinely considering patient BMI in risk stratification schemes or prognostic LNI models may not be warranted.     

MSKCC乳腺癌前哨淋巴结转移预测模型的验证性研究

目的验证并评估美国纪念斯隆-凯特琳癌症中心(MSKCC)前哨淋巴结转移预测模型在中国早期乳腺癌病人中的临床应用价值。方法回顾性分析复旦大学附属肿瘤医院乳腺外科2005年3月至2009年10月接受前哨淋巴结活检的524例乳腺癌病人的病历资料,探索前哨淋巴结转移相关的临床病理因素。利用MSKCC淋巴结转移预测模型计算每例病人前哨淋巴结转移风险,并以校正曲线和受试者操作特性曲线(ROC曲线)下面积(AUC)评估该模型在中国早期乳腺癌病人中的临床应用价值。结果发病年龄、肿瘤原发灶大小、肿瘤组织学分级、神经侵犯、脉管侵犯情况等因素与前哨淋巴结转移有关。其中,原发灶大小(OR1.429,95%CI1.142-1.788)和脉管情况(OR9.462,CI5.551-16.130)是独立的危险因素。校正曲线显示预测值曲线和真实值曲线趋势相同,MSKCC模型的AUC为0.757。结论 MSKCC淋巴结转移预测模型可较准确地应用于中国人群,作为术前评估工具具有较好的临床应用价值。     

Validation of a nomogram predicting the probability of lymph node invasion among patients undergoing radical prostatectomy and an extended pelvic lymphadenectomy

INTRODUCTION: Our goal was to develop and internally validate a nomogram for prediction of lymph node invasion (LNI) in patients with clinically localized prostate cancer undergoing extended pelvic lymphadenectomy (ePLND). METHODS: 602 consecutive patients (mean age 65.8 years) underwent an ePLND, where 10 or more nodes were removed. PSA was 1.1-49.9 (median 7.2). Clinical stages were: T1c in 55.6%, T2 in 41.4% and T3 in 3%. Biopsy Gleason sums were: 6 or less in 66%, 7 in 25.4%, 8-10 in 8.6%. Multivariate logistic regression models tested the association between all of the above predictors and LNI. Regression-based coefficients were used to develop a nomogram predicting LNI and 200 bootstrap resamples were used for internal validation. RESULTS: Mean number of lymph nodes removed was 17.1 (range 10-40). LNI was detected in 66 patients (11.0%). Univariate predictive accuracy for total PSA, clinical stage and biopsy Gleason sum was 63%, 58% and 73%, respectively. A nomogram based on clinical stage, PSA and Biopsy Gleason sum demonstrated bootstrap-corrected predictive accuracy of 76%. CONCLUSIONS: A nomogram based on pre-treatment PSA, clinical stage and biopsy Gleason sum can highly accurately predict LNI at ePLND.     

Percentage of positive biopsies predicts lymph node involvement in men with low‐risk prostate cancer undergoing radical prostatectomy and extended pelvic lymphadenectomy

Study Type – Diagnostic (exploratory cohort)
Level of Evidence 2b What’s known on the subject? and What does the study add? The current retrospective study evaluates predictive clinical parameters associated with lymph node metastasis in a homogeneous cohort of 499 men with low‐risk prostate cancer who underwent radical prostatectomy. Low‐risk profile and <50% of biopsies involved with cancer are strong predictors of metastasis‐free lymph nodes so that patients do not have to undergo extended pelvic lymphadenectomy.

OBJECTIVE

To evaluate preoperative predictive risk factors associated with lymph node metastases (LNM) in a cohort of low‐risk prostate cancer (PCA) patients.

PATIENTS AND METHODS

The charts of 499 patients were retrospectively reviewed to identify prognostic risk factors for the presence of LNM. Pathohistological data and Gleason score of the radical prostatectomy (RP) specimen, number of removed nodes, number of positive lymph nodes, and anatomical distribution of LNM were tabulated and evaluated. A correlation between clinical stage, preoperative serum prostate‐specific antigen (PSA), biopsy Gleason score, number of biopsies taken, percentage of positive biopsies and the presence of LNM were calculated. All 499 men underwent retropubic RP and extended pelvic lymphadenectomy (EPLND).

RESULTS

LNM were identified in 29 (5.8%) patients. A prediction model based on clinical stage, PSA, and biopsy Gleason score had a predictive accuracy of 79.2%. The addition of number of positive biopsies and % positive cores improved its predictive accuracy to 81.5% and 87.8%, respectively. The predicted frequency of LNM by the original nomogram was 7.4% and differed by less than 3% with the actual observation of LNM. The predictive accuracy of the nomogram was 81.5% as compared with 87.8% of the prediction model of this study.

CONCLUSIONS

The percentage of positive cores involved with PCA is the most reliable predictor of LNM and indicates the need for EPLND. The Briganti nomogram has been validated and a general applicability for predicting the presence of LNM was proven.     

Sentinel lymph node dissection for prostate cancer: experience with more than 1,000 patients

PURPOSE: We determined the incidence of positive pelvic lymph nodes in men undergoing radical retropubic prostatectomy and describe the correlation with prostate specific antigen, histological grade and stage. We examined whether tumor cells are localized in the sentinel nodes only or also in other nonsentinel lymph nodes. MATERIALS AND METHODS: A total of 1,055 men with prostate cancer underwent radio guided pelvic lymph node dissection and radical retropubic prostatectomy. In men with prostate specific antigen 20 ng/ml or less and biopsy Gleason score 7 or less only sentinel nodes were removed. In men with prostate specific antigen more than 20 ng/ml or Gleason score greater than 7 extended pelvic lymph node dissection was also performed. RESULTS: Positive lymph nodes were found in 207 men (19.6%). In 63.3% of the men these lymph nodes were detected outside of the region of standard lymphadenectomy. The percent of patients with positive nodes was greater than predicted by currently used nomograms. The higher the preoperative prostate specific antigen, pathological stage and grade, the greater the percent of men with positive sentinel and nonsentinel lymph nodes (p<0.001). CONCLUSIONS: When deciding on pelvic lymph node dissection, sentinel or extended lymphadenectomy should be performed since more than half of patients have positive nodes outside of the region of standard lymphadenectomy. In cases of positive sentinel nodes extended lymph node dissection should be performed since tumor cells are also detectable in nonsentinel lymph nodes.     

The prognostic impact of pelvic lymph node metastasis and lymphovascular invasion on bladder cancer

Objectives:   To present long-term results of a single-center series of patients undergoing bilateral pelvic lymphadenectomy and radical cystectomy for bladder cancer and to analyze the impact of pelvic lymph node metastasis and lymphovascular invasion on clinical outcome.
Methods:   Between 1986 and 2005 833 patients were treated with bilateral pelvic lymphadenectomy and radical cystectomy at our institution. 614 of them with valid clinical follow-up information and no neoadjuvant therapy could be evaluated.
Results:   Disease-free and overall survival in the entire cohort was 56.7% and 49.5% at 5 years and 52.4% and 38.2% at 10 years, respectively. 28.1% of all patients had pelvic lymph node metastasis. We found organ-confined tumor stages (≤pT2) in 43.8%. Patients with non-organ-confined tumor stages (≥pT3) and positive pelvic lymph nodes had a significantly shorter overall survival than those without lymph node metastasis ( P  < 0.0001). In the subgroup of ≤pT2, the presence of pelvic lymph node metastasis did not show a statistically significant effect on overall survival ( P  = 0.618). The presence of lymphovascular invasion was associated with an impaired survival ( P  < 0.0001). In multivariate analysis, pathological tumor stage ( P  < 0.0001), lymph node stage (≥pT3) ( P  = 0.004) and lymphovascular invasion ( P  = 0.001) were independent prognostic parameters.
Conclusions:   According to the present series, survival for patients with ≤pT2 does not depend on the lymph node stage. Lymphovascular invasion is an independent parameter of impaired survival and should be determined routinely in cystectomy specimens to identify patients, who may benefit from adjuvant systemic therapy.     

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.     

Impact of surgical volume on the rate of lymph node metastases in patients undergoing radical prostatectomy and extended pelvic lymph node dissection for clinically localized prostate cancer

BACKGROUND: Previous trials have shown that the number of procedures done by a single surgeon, that is, surgical volume (SV), is associated with several outcomes after radical prostatectomy (RP). OBJECTIVE: To test the association between SV and the detection of lymph node metastases during extended pelvic lymph node dissection (ePLND). DESIGN, SETTING, AND PARTICIPANTS: The study cohort consisted of 1020 men surgically treated for clinically localized prostate cancer. INTERVENTION: All patients underwent RP and ePLND by a group of six surgeons who were trained by the surgeon with the highest SV. All surgeons performed an anatomically extended PLND, including removal of obturator, external iliac, and hypogastric nodes. MEASUREMENTS: Univariable and multivariable logistic regression models tested the association between SV (either continuously coded or dichotomized according to the most informative cut-off, namely >144 vs /=0.06). Conversely, the surgeon with the highest SV removed more nodes and found more nodal metastases compared with the other surgeons (21.1 vs 17.9 mean number of nodes removed; p<0.001, and 15 vs 9.8% of LNI; p=0.01, respectively). At univariable logistic regression analysis, either continuously coded or dichotomized SV was a significant predictor of LNI (p=0.007 and p<0.001, respectively). In multivariable models, continuously coded as well as dichotomized SV maintained a significant association with the rate of LNI, after accounting for preoperative (p=0.04 and p=0.009, respectively) as well as for postoperative variables (p=0.03 and p=0.002, respectively). CONCLUSIONS: After adjusting for clinical and pathologic case-mix differences, patients treated by the highest-volume surgeons (>144 ePLNDs) were more likely to have LNI than those treated by low-volume surgeons, even though all surgeons used a similar extended template for node removal.     

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.