Elsevier

European Urology

Volume 72, Issue 4, October 2017, Pages 632-640
European Urology

Prostate Cancer
Development and Internal Validation of a Novel Model to Identify the Candidates for Extended Pelvic Lymph Node Dissection in Prostate Cancer

https://doi.org/10.1016/j.eururo.2017.03.049Get rights and content

Abstract

Background

Preoperative assessment of the risk of lymph node invasion (LNI) is mandatory to identify prostate cancer (PCa) patients who should receive an extended pelvic lymph node dissection (ePLND).

Objective

To update a nomogram predicting LNI in contemporary PCa patients with detailed biopsy reports.

Design, setting, and participants

Overall, 681 patients with detailed biopsy information, evaluated by a high-volume uropathologist, treated with radical prostatectomy and ePLND between 2011 and 2016 were identified.

Outcome measurements and statistical analysis

A multivariable logistic regression model predicting LNI was fitted and represented the basis for a coefficient-based nomogram. The model was evaluated using the receiver operating characteristic-derived area under the curve (AUC), calibration plot, and decision-curve analyses (DCAs).

Results and limitations

The median number of nodes removed was 16. Overall, 79 (12%) patients had LNI. A multivariable model that included prostate-specific antigen, clinical stage, biopsy Gleason grade group, percentage of cores with highest-grade PCa, and percentage of cores with lower-grade disease represented the basis for the nomogram. After cross validation, the predictive accuracy of these predictors in our cohort was 90.8% and the DCA demonstrated improved risk prediction against threshold probabilities of LNI ≤20%. Using a cutoff of 7%, 471 (69%) ePLNDs would be spared and LNI would be missed in seven (1.5%) patients. As compared with the Briganti and Memorial Sloan Kettering Cancer Center nomograms, the novel model showed higher AUC (90.8% vs 89.5% vs 89.5%), better calibration characteristics, and a higher net benefit at DCA.

Conclusions

An ePLND should be avoided in patients with detailed biopsy information and a risk of nodal involvement below 7%, in order to spare approximately 70% ePLNDs at the cost of missing only 1.5% LNIs.

Patient summary

We developed a novel nomogram to predict lymph node invasion (LNI) in patients with clinically localized prostate cancer based on detailed biopsy reports. A lymph node dissection exclusively in men with a risk of LNI > 7% according to this model would significantly reduce the number of unnecessary pelvic nodal dissections with a risk of missing only 1.5% of patients with LNI.

Introduction

Up to 15% of prostate cancer (PCa) patients harbor lymph node invasion (LNI) at radical prostatectomy (RP) [1]. These individuals are at a higher risk of recurrence after primary treatment [2]. Correct nodal staging is crucial to identify patients with poor prognosis who would benefit from additional therapies [3], [4]. The implementation of novel imaging modalities such as prostate-specific membrane antigen positron emission tomography /computed tomography scan prior to RP is limited by their poor performance characteristics [5]. Conversely, an anatomically defined extended pelvic lymph node dissection (ePLND) represents the most optimal method for nodal staging [6], [7]. Given the prolonged operative time as well as the increased risk of complications associated with an ePLND [8], [9], this procedure is indicated only in selected patients at a higher risk of nodal involvement [6], [7]. The European Association of Urology (EAU)–European Society for Radiotherapy & Oncology (ESTRO)–International Society of Geriatric Oncology (SIOG) and the National Comprehensive Cancer Network (NCCN) clinical guidelines recommend the use of models based on preoperative characteristics such as the Briganti and Memorial Sloan Kettering Cancer Center (MSKCC) nomograms to estimate the risk of LNI and, in turn, to select men who should be considered for an ePLND [10], [11], [12], [13]. However, these tools need to be periodically updated [14]. Moreover, although the Briganti and MSKCC nomograms achieve very good performance characteristics, they can certainly be improved [15]. Indeed, none of them included the precise assessment of cancer involvement within the biopsy cores or accounted for intraprostatic heterogeneity in PCa grade. This might lead to a limited accuracy in estimating the risk of LNI [10], [11], [13]. Under this light, we sought to develop a novel nomogram predicting LNI in a contemporary cohort of patients treated with RP and ePLND, with detailed biopsy information available after a centralized biopsy specimen review.

Section snippets

Population source and surgical procedure

After Institutional Review Board approval, clinical and pathologic data were prospectively collected for 2872 patients treated with open or robot-assisted RP and ePLND for localized PCa between January 2011 and July 2016 at a single tertiary referral center. Patients with complete data who underwent centralized biopsy specimens review performed by two high-volume dedicated uropathologists (either R.M. or M.F.) were selected (n = 681). No patients received neoadjuvant hormonal therapy. All cases

Baseline characteristics

Overall, 79 (12%) patients had LNI (Table 1). The median (IQR) number of lymph nodes removed was 16 (8–22). The sites for positive lymph nodes were the obturator fossa (n = 42; 53%); external (n = 34; 43%), internal (n = 20; 25%), and common (n = 9; 11%) iliac stations; and presacral area (n = 8; 9%). Preoperative PSA, biopsy grade group, percentage of positive cores, percentage of cores with highest-grade PCa, maximum percentage of single core involvement with highest- and lower-grade PCa, tumor length,

Discussion

Nodal staging is crucial to identify patients with localized PCa at a higher risk of adverse oncologic outcomes and plan their optimal management [1], [2], [3], [4]. Available imaging modalities are associated with suboptimal performance characteristics [5]. Therefore, an anatomically defined ePLND still represents the gold standard for the detection of nodal metastases [6], [7]. Given the potential morbidity associated with this procedure [8], [9], an ePLND should be considered only in men

Conclusions

An ePLND should be avoided in patients with detailed biopsy information and a risk of nodal involvement below 7%, according to our newly developed nomogram to predict LNI in order to spare approximately 70% ePLNDs at the cost of missing only 1.5% patients with node-positive PCa.

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