Sensitivity and specificity of Briganti nomogram in Turkish patients undergoing radical prostatectomy and pelvic lymph node dissection

Abstract

Aim

To investigate the accuracy of Briganti nomogram in patients who underwent Pelvic lymph node dissection (PLND).

Methods

Hundred and sixty-five patients who underwent radical prostatectomy and PLND between 2012 and 2018 in our clinics were included, and their data were retrospectively screened.

Results

The mean age of patients was 63.6 ± 5.8 (range: 49–76) years. Hundred and thirty-five (81.8%) patients had a Briganti score of <5, whereas 30 (18.2%) had a Briganti score of ≥5. The preoperative T-PSA levels, biopsy grades and the incidence of T2b and T2c stages in patients with a Briganti score of ≥5 was significantly higher than that in patients with a Briganti score of <5 (p: .026; p: .000; p: .001, respectively). The incidence of lymph node positivity in patients with a Briganti score of ≥5 (76.7%) was significantly higher than that in patients with a Briganti score of <5 (25.2%) (p: .000). The sensitivity of the Briganti score to detect lymph node positivity was 40.35%, specificity was 93.52%, positive predictive value was 76.67% and the negative predictive value was 74.81%. The accuracy of the test was 75.15%.

Conclusion

Nomograms provide useful information regarding prostate cancer. Risk estimates should be carefully considered, and treatment decisions should be given with a patient-specific approach.

Keywords:

• Briganti nomogram
• prostate cancer
• pelvic lymph node
• invasion
• radical prostatectomy

Introduction

Prostate cancer is the most commonly diagnosed cancer in men [1]. Treatment options are varied but radical prostatectomy is the preferred modality in patients with localized prostate cancer and life expectancy of more than 10 years, even for elderly patients aged 75 years or older [2]. The most effective method for the detection of pelvic lymph node metastasis in prostate cancer is pelvic lymph node dissection (PLND) because the accuracy of standard imaging methods is insufficient. PLND determines prognosis and the need for adjuvant treatment after surgery by providing accurate staging. For this reason, PLND has a fundamental role in the management of patients with prostate cancer [3–5]. PLND is generally indicated in patients with PSA >10 ng/mL and PSA <10 ng/mL and a Gleason score of ≥7 [6]. Appropriately performed PLND should extend from the external iliac veins in the obturator fossa to the point where the ureter crosses over the common iliac vessels along the internal iliac vessels. The European Association of Urology Guidelines recommends PLND to patients with a risk of lymph node metastasis of >5% according to the nomogram incorporating PSA, clinical stage, biopsy Gleason score, and positive core ratio [7]. Despite advances in radiological techniques, computed tomography and magnetic resonance imaging are not routinely recommended because of their low sensitivity (0–30%) in detecting lymph node metastases [8,9]. Moreover, the most important drawback of imaging techniques is that they cannot adequately describe micrometastatic nodes that are expected to benefit from PLND. Monoclonal antibody radioimmunoscintigraphy has been shown to have limited efficacy in detecting lymph node metastases [10]. Studies have shown that ProstaScint has low positive predictive value (11%) and sensitivity (17%) in detecting lymph node metastasis [11]. In addition, technetium-based lymphoscintigraphy can miss out diseased lymph nodes up to 30% [12]. In summary, PLND is the most accurate and reliable staging procedure in terms of determining lymph node metastasis. Extensive research has been performed in this regard, but neither imaging techniques nor lymphoscintigraphy has replaced PLND because of their low sensitivity. In our study, we aimed to investigate the predictive accuracy of Briganti nomogram [4] in Turkish patients who underwent PLND.

Materials and methods

Hundred and sixty-five patients who underwent radical prostatectomy and PLND with the diagnosis of prostate cancer between 2012 and 2018 in our clinics were included, and their data were retrospectively screened. The same two surgeons performed operations, and the same anatomic template was applied for ePLND. Standard radical retropubic prostatectomy was performed with a lower midline incision. The decision to perform PLND was made before surgery. Extended lymph node dissection was performed from the iliac veins to the point where the ureter crosses over the common iliac vessels including obturator fossa up to the obturator nerve and along the course of iliac vessels. In our study, the number of removed lymph nodes from one side ranged from 8 to 17, with a median of 12.

Patient demographics, histopathologic features, and operative details were retrospectively obtained from the Health Information Systems (HIS). All histological specimens were independently reviewed by an uropathologists. Collected data of patients were calculated using the Briganti 2012 nomogram: “Prediction of lymph node involvement in patients with prostate cancer.” In addition, patients receiving neoadjuvant hormonotherapy were excluded from the study. The biopsy indication in patients included in the study was based on the presence of suspicious findings on digital rectal examination and elevation of serum PSA levels. Systematic 12 core transrectal prostate biopsy was performed to all patients. None of the patients had preoperative multiparametric MRI and underwent targeted biopsy (cognitive or fusion).

Statistical analysis

Data obtained were evaluated using the IBM SPSS Statistics 22 program for statistical analyses. In the evaluation of study data, Shapiro–Wilks test was used to check whether parameters were normally distributed. In addition to descriptive statistical methods (mean, standard deviation, frequency) in the analysis of quantitative data, Student’s t-test was used to compare normally distributed parameters between the two groups and Mann–Whitney U test was used to compare parameters without normal distribution between the two groups. Fisher-Freeman-Halton’s test and Yates’s correction for continuity were used to compare qualitative data. Diagnostic screening tests were used for sensitivity and specificity calculations. The level of significance was set at a p value of <.05.

Results

A total of 165 male patients aged between 49 and 76 years were included. The mean age of patients was 63.67 ± 5.88 years. BMI ranged from 19 kg/m² to 35 kg/m² with a mean of 25.66 ± 3.27 kg/m². The Briganti score ranged from 1 to 36, with a mean of 3.34 ± 4.62 and median of 2. Hundred and thirty-five (81.8%) patients had a Briganti score of <5, whereas 30 (18.2%) had a Briganti score of ≥5. Lymph nodes were positive in 57 (34.5%) patients.

There was no statistically significant difference between patients with a Briganti score of <5 and those with a Briganti score of ≥5 in terms of mean age and BMI (p > .05). The incidence of T2b and T2c stages in patients with a Briganti score of ≥5 was significantly higher than that in patients with a Briganti score of <5 (p: .001). There was no statistically significant difference between patients with a Briganti score of <5 and those with a Briganti score of ≥5 in terms of prostate volume in pathologic evaluation (p > .05). The preoperative T-PSA levels of patients with a Briganti score of ≥5 were significantly higher than those of patients with a Briganti score of <5 (p: .026). The biopsy grades of patients with a Briganti score of ≥5 were significantly higher than those of patients with a Briganti score of <5 (p: .000). The ISUP levels of patients with a Briganti score of 5 and higher were significantly higher than those with a Briganti score below 5 (p: .000). The positive biopsy levels of patients with a Briganti score of ≥5 were significantly higher than those of patients with a Briganti score of <5 (p: .000). The pathological grades of patients with a Briganti score of ≥5 were significantly higher than those of patients with a Briganti score of <5 (p: .001). The incidence of lymph node positivity in patients with a Briganti score of ≥5 (76.7%) was significantly higher than that in patients with a Briganti score of <5 (25.2%) (p: .000) (Table 1). The sensitivity of the Briganti score to detect lymph node positivity was 40.35%, specificity was 93.52%, positive predictive value was 76.67% and the negative predictive value was 74.81%. The accuracy of the test was 75.15%.

Table 1. Evaluation of study parameters according to the Briganti nomogram.

	Briganti score < 5 (n = 135)	Briganti score ≥ 5 (n = 30)	p
AgeMean±SD	63.61 ± 5.94	63.97 ± 5.68	^a.763
Body mass indexMean±SD	25.5 ± 3.17	26.4 ± 3.64	^a.172
Clinical stagen,%
T1c	88 (%65.2)	11 (%36.7)	^b.001*
T2	47 (%34.8)	19 (%63.3)
Prostate volumeMean±SD (median)	50.76 ± 23.45 (45)	50.7 ± 27.04 (40.5)	^c.714
Preoperative T-PSAMean±SD(median)	7.5 ± 4.21 (6.8)	11.36 ± 9.29 (7.9)	^c.026*
Biopsy GradeMean±SD (median)	6.13 ± 0.46 (6)	6.73 ± 0.58 (7)	^c.000*
ISUPMean±SD (median)	1.19 ± 0.43 (1)	2.1 ± 0.96 (2)	^c.000*
% of positive biopsiesMean±SD (median)	23.7 ± 14.18 (20)	55.72 ± 26.18 (50)	^c.000*
Pathologic GradeMean±SD (median)	6.33 ± 0.57 (6)	6.77 ± 0.63 (7)	^c.001*
Lymph noden,%
LN−	101 (%74.8)	7 (%23.3)	^d.000*
LN+	34 (%25.2)	23 (%76.7)

^a Student t-test.

^b Fisher Freeman Halton test.

^c Mann–Whitney U Test.

^d Continuity (yates) correction test *p < .05.

Discussion

The rate of lymph node involvement in prostate cancer depends on several factors, such as PSA level, Gleason score, and clinical stage of patients. The presence of lymph node metastasis in men diagnosed with clinically localized prostate cancer indicates a poor prognosis. The presence of lymph node metastasis has not only prognostic significance but also therapeutic importance. An appropriate adjuvant treatment can be planned by determining the risk of progression. Although the presence of lymph node metastasis directly correlates with T stage, biopsy grade, and PSA levels, PLND is the most accurate method for detecting occult metastases [13]. Although pelvic lymphadenectomy is an accurate method of detecting metastases, in clinical practice, nomograms such as the Memorial Sloan Kettering Cancer Center, Partin, and Briganti, which can predict pelvic lymph node metastasis, are used in patients diagnosed with prostate cancer. In our study, we retrospectively analyzed patients undergoing radical prostatectomy and PLND and evaluated the accuracy of Briganti scoring in our series.

In our study, the rate of lymph node invasion in patients who underwent radical prostatectomy and lymph node dissection was 34.5%. When patient characteristics were examined, the clinical stage was T1c in 60% and T2 in 40% of patients. In a study by Heindreick et al., the rate of lymph node invasion was 26%, with only 8.7% having clinical T1c disease [14]. In contrast, Walz et al. in their series reported the rate of lymph node invasion as 6.9%. In this series, 72% of patients had clinical T1c with better prognosis [15]. Similarly, the rate of lymph node invasion reported by Nason et al. was 9.7%, with 48% of them having clinical T1c disease [16]. The rate of lymph node invasion was higher in our study than in studies reported in the literature [14–16]. In our study, the number of removed lymph nodes from one side ranged from 8 to 17, with a median of 12.

The primary aim of the curative prostate cancer treatment is improvement of survival and quality of life [17–19]. Therefore, there are many pretreatment factors defined in order to predict the course of prostate cancer such as: genomic tests, parameters detected on prostate biopsies, clinical and pathological nomograms [20,21]. Until today, nomograms have been used to predict the risk of lymph node invasion in patients with prostate cancer. Cutoff values have been proposed for several nomograms, and it has been suggested that lymph node dissection cannot be performed below these cutoff values. In our study, a cutoff value of 5 was accepted for the Briganti score. Further, 81.8% of our patients had a Briganti score of <5, whereas only 18.2% had a Briganti score of >5. In 25.2% (34/135) of patients with a Briganti score of <5, pathologic lymph node positivity was present. On the other hand, Hansen et al. accepted cut off value as 4% and in 10% of patient had pathological lymph node positivity while Briganti nomogram score below 4% [22]. In our study the sensitivity of the Briganti nomogram in predicting lymph node invasion was 40.35%; the specificity was 93.52%; positive predictive value was 76.67%; negative predictive value was 74.81%, and the accuracy was 75.15%. According to a study conducted by Briganti et al., the sensitivity, specificity, and negative predictive value associated with the 5% cutoff were 87.8%, 70.3%, and 98.4% respectively [23]. Also in a study conducted by Gacci et al., predictive accuracy of Briganti nomogram was 79% [24]. On the other hand in a study conducted by G. J. Nason et al. on 103 patients who underwent radical prostatectomy and lymph node dissection, the cutoff value for Briganti score was accepted as 2.5, and this value was found to be >2.5 in only three patients. The negative predictive value for Briganti score was reported as 88.5% [16]. In our study, the negative predictive value for Briganti score was 74.81%. In another study conducted by Bandini et al. on a large series of patients, the cutoff value for the Briganti nomogram was 4.6 and pathologic lymph node positivity was found in 10% of patients below this score. The sensitivity of the Briganti nomogram was reported as 90% and specificity was 46.1% [25]. In our study, pathological lymph node positivity was detected in 25.2% of patients with a Briganti score of <5. Compared with series in the literature, the negative predictive value and specificity of the Briganti score in our series were lower, which might be because our cut off value for Briganti nomogram was 5% and also clinical T stage could be variable according to physical examination. Because of that our clinical T stage values could be higher. Clinical T stage does not dependent on imaging studies and it could be changed according to physical examination of urologist. Lately, to resolve this conflict, Briganti nomogram was updated and clinical T stage is obtained according to multiparametric MRI [24]. Also in our series pathological lymph node invasion is higher than series in literature. This could be also a reason for lower negative predictive value and specificity of Briganti score.

In recent years, in addition to cancer nomograms, ⁶⁸Ga prostate-specific membrane antigen positron emission computerized tomography (⁶⁸Ga-PSMA PET/CT) has achieved worldwide attention as a novel imaging technique to diagnose lymph node metastasis, prostate cancer diagnosis and tumor burden evaluation [26,27]. Also, a former study showed that ¹¹C-choline PET/CT outperformed prostate cancer nomograms in diagnosing lymph node metastasis [28].

The main limitations of our study were its retrospective design and none of the patients had preoperative multiparametric MRI and underwent targeted biopsy (cognitive or fusion). The Briganti nomogram updated itself to provide more effective and accurate results and updated the t-stage section to clinical stage at multiparametric MRI. In this way, the predictive value of the nomogram is stated to be higher and more reliable.

Conclusion

Nomograms provide useful information regarding prostate cancer; however, prostate cancer genetics in different populations and possible geographic factors are not taken into account. Therefore, in this study, we evaluated the predictive accuracy of Briganti nomogram in Turkish population. Risk estimates should be carefully considered, and although nomograms have predictive value, treatment decisions should be given with a patient-specific approach.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Disclosure statement

The authors declare that they have no conflict of interest.