Low serum total testosterone level as a predictor of upstaging and upgrading in low-risk prostate cancer patients meeting the inclusion criteria for active surveillance.

Matteo Ferro,Vincenzo Mirone,Amelia Cimmino,Rocco Damiano,Roberto La Rocca,Michele Battaglia,Giuseppe Di Lorenzo,Carlo Buonerba,Giuseppe Lucarelli,Daniela Terracciano,Dario Bruzzese,Ottavio De Cobelli,Francesco Cantiello,Sisto Perdonà,Riccardo Autorino,Gian Maria Busetto

doi:10.18632/oncotarget.12906

Abstract

Active surveillance (AS) is currently a widely accepted treatment option for men with clinically localized prostate cancer (PCa). Several reports have highlighted the association of low serum testosterone levels with high-grade, high-stage PCa. However, the impact of serum testosterone as a predictor of progression in men with low-risk PCa has been little assessed.In this study, we evaluated the association of circulating testosterone concentrations with a staging/grading reclassification in a cohort of low-risk PCa patients meeting the inclusion criteria for the AS protocol but opting for radical prostatectomy.Radical prostatectomy (RP) was performed in 338 patients, eligible for AS according to the following criteria: clinical stage T2a or less, PSA<10ng/ml, two or fewer cancer cores, Gleason score (GS)=6 and PSA density<0.2 ng/mL/cc. Reclassification was defined as upstaging (stage>pT2) and upgrading (GS=7; primary Gleason pattern 4) disease. Unfavorable disease was defined as the occurrence of pathological stage>pT2 and predominant Gleason score 4. Total testosterone was measured before surgery.Low serum testosterone levels (<300 ng/dL) were significantly associated with upgrading, upstaging, unfavorable disease and positive surgical margins. The addition of testosterone to a base model, including age, PSA, PSA density, clinical stage and positive cancer involvement in cores, showed a significant independent influence of this variable on upstaging, upgrading and unfavorable disease.In conclusion, our results support the idea that total testosterone should be a selection criterion for inclusion of low-risk PCa patients in AS programs and suggest that testosterone level less than 300 ng/dL should be considered a discouraging factor when a close AS program is considered as treatment option

Highlights

Active surveillance (AS) has recently emerged as an alternative treatment for patients with lowrisk prostate cancer (PCa)-related mortality, whereby curative intervention can be delayed until the time that disease is re-classified or there is evidence of disease progression [1]
We explored the impact of serum testosterone on upgrading, upstaging, unfavorable disease, positive surgical margins and predominant Gleason score 4 in a cohort of patients with very low-risk PCa who met the inclusion criteria for Prostate Cancer Research International: Active Surveillance (PRIAS) protocol, but elected to undergo radical prostatectomy (RP)
Total testosterone included in these base models was a significant independent predictor, both as a continuous and dichotomous variable, of upstaging, upgrading and unfavorable disease

Summary

INTRODUCTION

Active surveillance (AS) has recently emerged as an alternative treatment for patients with lowrisk prostate cancer (PCa)-related mortality, whereby curative intervention can be delayed until the time that disease is re-classified or there is evidence of disease progression [1]. We explored the impact of serum testosterone on upgrading, upstaging, unfavorable disease, positive surgical margins and predominant Gleason score 4 in a cohort of patients with very low-risk PCa who met the inclusion criteria for Prostate Cancer Research International: Active Surveillance (PRIAS) protocol, but elected to undergo radical prostatectomy (RP). When treated as a continuous variable, lower total testosterone levels (median [IQR]) were associated with reclassification in terms of upstaging (299.5 [250 ; 390] vs 488.5 [401 ; 600]; p < 0.001), upgrading (400.5 [292.25 ; 534] vs 497.5 [401 ; 600]; p < 0.001), unfavorable disease (290 [250 ; 300] vs 456 [390 ; 567]; p < 0.001) and predominant Gleason score 4 (300 [254 ; 502] vs 477 [398 ; 597]; p < 0.001).

RESULTS

DISCUSSION

MATERIALS AND METHODS