Pathologic Nodal Staging Scores in Patients Treated with Radical Prostatectomy: A Postoperative Decision Tool

Abstract

Background

Nodal metastasis is the strongest risk factor of disease recurrence in patients with localized prostate cancer (PCa) treated with radical prostatectomy (RP).

Objective

To develop a model that allows quantification of the likelihood that a pathologically node-negative patient is indeed free of nodal metastasis.

Design, setting, and participants

Data from patients treated with RP and pelvic lymph node dissection (PLND; n = 7135) for PCa between 2000 and 2011 were analyzed. For external validation, we used data from patients (n = 4209) who underwent an anatomically defined extended PLND.

Intervention

RP and PLND.

Outcome measurements and statistical analysis

We developed a novel pathologic (postoperative) nodal staging score (pNSS) that represents the probability that a patient is correctly staged as node negative based on the number of examined nodes and the patient's characteristics.

Results and limitations

In the development and validation cohorts, the probability of missing a positive node decreases with an increasing number of nodes examined. Whereas in pT2 patients, a 90% pNSS was achieved with one single examined node in both the development and validation cohort, a similar level of nodal staging accuracy was achieved in pT3a patients by examining five and nine nodes, respectively. The pT3b/T4 patients achieved a pNSS of 80% and 70% when 17 and 20 nodes in the development and validation cohort were examined, respectively. This study is limited by its retrospective design and multicenter nature. The number of nodes removed was not directly correlated with the extent/template of PLND.

Conclusions

Every patient needs PLND for accurate nodal staging. However, a one-size-fits-all approach is too inaccurate. We developed a tool that indicates a node-negative patient is indeed free of lymph node metastasis by evaluating the number of examined nodes, pT stage, RP Gleason score, surgical margins, and prostate-specific antigen. This tool may help in postoperative decision making.

Introduction

Prostate cancer (PCa) is the most common noncutaneous malignancy in men with an estimated 238 590 new cases and 29 720 deaths in 2013 in the United States [1]. Radical prostatectomy (RP) provides good long-term local control and survival when cancer is confined to the prostate [2], [3]. In patients with locally advanced disease [4], [5], [6], [7], such as extraprostatic extension and lymph node (LN) metastasis [8], [9], [10], adjuvant radiation therapy (RT) and androgen-deprivation therapy (ADT) have improved disease-free recurrence and survival rates.

Nodal metastasis is the strongest risk factor for disease recurrence and survival for patients treated with RP [2]. To achieve accurate LN staging, pelvic lymph node dissection (PLND) is necessary in patients undergoing RP [2], [11]. However, the rate and extent of PLND over the last decades has been decreasing, leading to a loss of accuracy of true LN status [11], [12]. LN dissemination in PCa does not follow a predefined pathway of metastatic spread but rather different lymphatic routes tributary to several primary lymphatic landing sites [13], [14]. Many efforts have been made to estimate the number of LNs needed to be removed and examined to achieve an accurate LN staging [15], [16], [17]. However, to date, no consensus has been reached on such a number. This issue is key because node-negative patients treated with inadequate extent of nodal dissection may harbor a non-negligible risk of residual or recurrent nodal disease after RP.

We recently developed a methodology that calculates the probability that a pathologic node-negative patient is indeed free of nodal metastasis as a function of the number of examined LNs and tumor stage in colorectal and bladder cancer [18], [19]. The aim of this study was to develop a similar pathologic nodal staging score (pNSS) for patients with PCa. We hypothesized that the true nodal status (no false-negative LN status) could be accurately predicted based on the number of LNs examined, pathologic characteristics such as pT stage, RP Gleason score, surgical margin, and preoperative prostate-specific antigen (PSA). Toward this goal, we used a large multicenter cohort of patients treated with RP and a variable extent of PLND to develop the novel nodal staging score (NSS). We subsequently validated the novel model in a large single-center cohort of RP patients who underwent an anatomically defined extended PLND (ePLND).