Low endogenous testosterone levels are associated with the extend of lymphnodal invasion at radical prostatectomy and extended pelvic lymph node dissection

Antonio Benito Porcaro,Rossella Orlando,Carmelo Monaco,Maria Angela Cerruto,Sebastian Gallina,Filippo Migliorini,Alberto Bianchi,Riccardo Rizzetto,Matteo Brunelli,Clara Cerrato,Alessandra Gozzo,Nelia Amigoni,Alessandro Tafuri,Stefano Zecchini Antoniolli,Alessandro Antonelli

doi:10.1007/s11255-021-02938-z

Abstract

ObjectiveTo investigate clinical factors associated to lymphnodal metastasis load in patients who underwent to radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND).Materials and methodsBetween November 2014 and December 2019, ET was measured in 617 consecutive patients not under androgen deprivation therapy who underwent RP and ePLND. Lymphnode invasion (LNI) was codified as not present (N = 0) or with one (N = 1) or more than one metastatic node (N > 1). The risk of multiple pelvic lymph node metastasis (N > 1, mPLNM) was assessed by comparing it to the other two groups (N > 1 vs. N = 0 and N > 1 vs. N = 1). Then, we assessed the association between ET and lymphnode invasion for standard predictors, such as PSA, percentage of biopsy positive cores (BPC), tumor stage greater than 1 (cT > 1) and tumor grade group greater than two (ISUP > 2).ResultsOverall, LNI was detected in 70 patients (11.3%) of whom 39 (6.3%) with N = 1 and 31 (5%) with N > 1. On multivariate analysis, ET was inversely associated with the risk of N > 1 when compared to both N = 0 (odds ratio, OR 0.997; CI 0.994–1; p = 0.027) as well as with N = 1 cases (OR 0.994; 95% CI 0.989–1.000; p = 0.015).ConclusionsIn clinical PCa, the risk of mPLNM was increased by low ET levels. As ET decreased, patients had an increased likelihood of mPLNM. Because of the inverse association between ET and mPLNM, higher ET levels were protective against aggressive disease. The influence of locally advanced PCa with high metastatic load on ET levels needs to be explored by controlled trials.

Highlights

Prostate cancer (PCa) worldwide is the second most incident solid cancer and represents a pivotal health related problem for the aging male [1]
With the present study we investigated the hypothesis that Endogenous testosterone (ET) levels could be associated with the lymphnodal metastatic burden in patients undergoing radical prostatectomy (RP) with extended pelvic lymph node dissection (ePLND)
Evaluating model II, the risk of multiple pelvic lymph node metastases (mPLNM) was increased by ET levels up to the first quartile after adjusting for body mass index (BMI), PSA, biopsy positive cores (BPC) and International Society of Urological Pathology (ISUP) > 2; model accuracy improved from 64.3% up to 74.3%

Summary

Introduction

Prostate cancer (PCa) worldwide is the second most incident solid cancer and represents a pivotal health related problem for the aging male [1]. Lymphnode dissection with an extended template (ePLND) should be performed when the risk of lymphnodal invasion exceeds 5%, according to the estimation provided by integrated predictive systems based on preoperative features [2]. Any available diagnostic tool to date suffers from significant inaccuracy concerning lymphnodal staging in PCa and, the main objective of ePLND remains the correct definition of lymphnodal involvement. Endogenous testosterone (ET) levels have a well-established role with the development and progression of PCa, showing significant associations with tumor biology. The relationship between pre-operative testosterone serum levels and prostate cancer stage and grade is debated. Some evidence suggests a linear correlation between pre-operative androgen levels and aggressiveness of PCA [5, 6]. Other authors found that low levels of testosterone are associated with more aggressive PCA [7–10]. In the recent literature, a very few studies are present on the relationship between testosterone levels and nodal invasion

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Results

Conclusion